Inflammatory bowel disease: The role of commensal microbiome in immune regulation

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González”, Monterrey, NL, Mexico" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad inflamatoria intestinal: el rol de microbioma comensal en la regulación inmune" ] ] "textoCompleto" => "IntroductionInflammatory bowel disease (IBD) epidemiology has changed over time. There is an increase in prevalence and incidence in many countries. The reports of IBD epidemiology models forecasts that IBD prevalence will increase by 3% per year, rising in prevalence from 0.7% in 2018 to 1% by 2030.<a class="elsevierStyleCrossRef" href="#bib0330">1</a> IBD epidemiology is heterogeneous among different countries; however, regions with a lower prevalence such as Latin America, have had an increased incidence in the last decades, as in Brazil and Mexico.<a class="elsevierStyleCrossRefs" href="#bib0335">2,3</a> Therefore, it is burdensome to establish an accurate incidence or prevalence in IBD worldwide but there is a trend toward an increase.The changes in incidence have not been fully explained. IBD is recognized as a multifactorial disease that can affect the small or large intestine in many different ways. It is still difficult to establish a relationship of causality; however, there is enough rationale to presume that the synergy among environmental, genetic, and compositional changes in intestinal microbiome could predispose the development of IBD. Multiple environmental determinants, such as antibiotic use, breastfeeding, air pollution and other urban conditions, influence the risk of developing IBD and can alter the natural history of IBD from perinatal development to adulthood.<a class="elsevierStyleCrossRef" href="#bib0345">4</a> In terms of genetics, genetic and epigenetic changes were found in IBD that can trigger different disease phenotypes; e.g., severity and cancer propensity. This precision medicine information requires more aggressive surveillance and treatment in patients.<a class="elsevierStyleCrossRef" href="#bib0350">5</a> Moreover, there is an association between an altered microbiome in IBD called dysbiosis, which results in a different metagenomic and metabolomic profile, and different concentrations of metabolic compounds in feces.<a class="elsevierStyleCrossRef" href="#bib0355">6</a>The purpose of this review is to summarize the current association between commensal microbiome and immune regulation in healthy individuals and IBD patients, and discuss the potential treatments related to modifications in the microbiome in human IBD.MethodsSearch strategiesWe searched for articles published in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov with the following MeSH terms for IBD and commensal bacteria: “Microbiota”, “Commensal”, “Dysbiosis”, “IBD”, “Ulcerative colitis”, “Crohn's disease”, “Gastrointestinal immune”. Then, the results were combined using “AND” with studies identified by other keywords such as “Ulcerative colitis”, “Crohn's disease”, “Prebiotics”, “Probiotics”, “Antibiotics”, “Faecal microbiota transplant”, “IBD therapy”, “Meta-analysis”. We enrolled all relevant data up to April 2020 by reviewing the titles and abstracts. The reference lists of relevant articles were also scrutinized.Data collection and quality assessment of studiesThe methodological quality of the current study includes case reports, cohort studies, random clinical trials (RCTs) and reviews and meta-analysis. The risk of bias in the information included depends on the level of evidence according to the type of study.Normal immune regulationThe immunologic system is composed of innate and adaptative responses. In the latter are the classical Th1 and Th2 immune response theory where different production of cytokines with interferon-γ (IFN-γ) for Th1 cells to attack intracellular organisms and interleukin (IL)-4, IL-5, and IL-13 for Th2 cells for parasitic infections. Another immunologic pathway with Th17 cells can raise IFN-γ effects that are similar to Th1 response, but also target innate immunity through neutrophil activity and epithelial cells response.<a class="elsevierStyleCrossRef" href="#bib0360">7</a> The cytokine IL-23, an important component in the cascade of Th17 cells acts as an effector of T cell subsets and it is involved in many responses that cause inflammation. CD4+Th17 are not found in the germ-free mouse intestines, showing that are generated according to microbiota and external stimuli. Some reports indicated that Il17A deficient mice caused increased colitis associated to high levels of IFN-γ due to the lack of inhibition of Th1 cells pathway. After all the subsets of T cells are in a steady sate, antigen presentation cells favor development of regulatory T cells (Tregs) that act to suppress inflammation by suppressing effector T cells.<a class="elsevierStyleCrossRef" href="#bib0365">8</a>Intestinal epithelial cells (IECs) and mesenchymal are important as barrier function and host response to infection and tissue damage as well. IECs are not only a barrier but also the beginning of the innate immune response to tissue damage; the balance of immune response is between NF-κB and STAT3 signaling pathways. Different cytokines induce activation, proliferation and inflammation-driven repair pathways in IECs including IL-6, IL-11, and IL-22 through STAT3 signals stimulation.<a class="elsevierStyleCrossRef" href="#bib0370">9</a> The mesenchymal cells underlying IECs in another important component in immune system. NOD2 activation through mesenchymal cells protects against enteric pathogens, and provides differentiation factors for IECs stems cells for repair.<a class="elsevierStyleCrossRef" href="#bib0375">10</a>Microbiota in immune-regulationThe gastrointestinal tract has an enriched number of microorganisms that interact with the immune system to produce certain types of signals depending on the entity involved. Different bacteria harbored in the intestine are well tolerated by the immune system because of the host genetic code or a response induced by bacteria; this process is called tolerogenic response.<a class="elsevierStyleCrossRef" href="#bib0380">11</a> The signal between the microbe and the host is reciprocal at several levels and is interconnected by a mutual regulation of development and homeostasis. The detection of disarrays in the components that are related in this interaction between microorganisms and intestinal environment is responsible for a cascade that triggers an inflammatory process. This inflammatory process ends in the abrupt increment of frequency of oncologic, liver, and inmmunoallergic processes, including IBD.<a class="elsevierStyleCrossRef" href="#bib0385">12</a>The microbiome is not constant during the lifespan and changes with age. Every segment of the gastrointestinal tract influences the concentration and type of microbiome.<a class="elsevierStyleCrossRef" href="#bib0390">13</a> Microbiota diversity depends on diet as well. The type of diet influences the plasticity of microorganisms living in the gastrointestinal tract. A diet rich in animal products enhances bile tolerant bacteria (Alistipes, Bilophila, and Bacteroides) and depletes others that metabolize plants, such as Firmicutes.<a class="elsevierStyleCrossRef" href="#bib0395">14</a> The growth dynamics of microbiota is very diverse and includes all kingdoms of organisms, such as prokaryotes, eukaryotes and viruses. The introduction of specialized databases with metagenomics has consistently allowed the classification of more than 30 prokaryotic phyla, finding human eukaryotic microbiome as pathogens, commensals and beneficial organisms, and identifying bacteriophages that keeps the gut in healthy homeostasis.<a class="elsevierStyleCrossRef" href="#bib0390">13</a>The role of different organisms as pathogenic or commensal is still an area of study. Some studies showed specific bacteria that help in several ways in mucin production, such as Akkermansiamuciniphila which changes mucus characteristics that improves barrier function and affects homeostasis. Commensals, such as Faecalibacterium prausnitzii needs an environment enriched with mucin to colonize the intestine. Furthermore, different bacteria byproducts like butyrate, boosts the growth of commensal bacteria.<a class="elsevierStyleCrossRef" href="#bib0400">15</a> Likewise, a few fungal microbiota are considered mycobiota in the gastrointestinal tract; this includes Candida, Saccharomyces, Penicillium, and Aspergillus; however some data argue against fungal colonization and suggest that fungi are not common colonization flora. It is debated whether the fungal microbiota is able to colonize as commensals, like bacteria, or is external contamination from the mouth or diet.<a class="elsevierStyleCrossRef" href="#bib0405">16</a>The progress of genetic profiling, including proteomics, metagenomics, and metabolomics, has contributed to the discovery of the composition of complex microbial communities of not only bacteria, but also many other microorganisms. This can help elucidate the change in microbiota as a cause of diseases.Pathogenesis in IBDImmune-regulation in IBDIBD is involved in the whole process of immune regulation including innate and adaptative mechanisms. The disease pathogenesis is multifactorial and complex through different immune abnormalities. Innate immunity involving neutrophils, monocytes, and macrophags respond to invading bacteria. These cells accumulate in inflamed intestines in UC and CD in the form of neutrophil-enriched crypt abscesses and granulomas, respectively. NOD2, which is the strongest predictor of CD, is associated with defects in innate immunity. Furthermore, TGF-β is another regulator of intestinal inflammation which is impaired by the inhibition with molecules like SMAD 7.<a class="elsevierStyleCrossRef" href="#bib0375">10</a>Dysfunctional Tregs activity, disrupt T and B cell activation and decreased innate immune system are implicated in auto-inflammatory responses. Th1, Th2, and Th17 cells subsets are arranged in different levels of the pathogenesis of IBD. The main signaling defects that lead to infantile IBD are IL-10 signaling. IL-10 has an important role in intestinal homeostasis, mice with IL-10 knock out develop colitis.<a class="elsevierStyleCrossRef" href="#bib0375">10</a> It is controversial the exact mechanism of Th17 cells in the pathogenesis of CD, however populations of CD4 T cells with CCR6+, IL-23R+, and CD 161+ are present in patients with IBD lesions. CD is associated with defects in autophagy, bacterial sensing, and excessive Th17 pathway activation.<a class="elsevierStyleCrossRef" href="#bib0410">17</a> In UC, genetic studies linked IL23 receptor and Th17 pathway to immune responses. IL-23 promotes survival of Th17 cells during inflammatory response; it increases cytokines such as granulocyte-macrophage colon stimulating factor and IFN-γ and inhibits intestinal Tregs cells response. Another cytokine is IL-13 which excessive production is implicated in pathogenesis by the natural killer T cells, defects in epithelial barrier integrity and excessive Th17 pathway activation.<a class="elsevierStyleCrossRef" href="#bib0360">7</a>Mesenchymal cells are involved in the pathogenesis of IBD and have implications in its treatment. IL-6 family cytokine Oncostatin M (OSM) and its receptor are increased in active CD and UC. Moreover, inflammatory monocytes and inflammation-associated fibroblasts (IAFs) are augmented in inflamed tissue of IBD patients. These types of cells intervene in medication resistance through OSM and its receptor pathways.<a class="elsevierStyleCrossRefs" href="#bib0375">10,18</a>Different recognized targets such as IL-1 receptor, anti-TNF, anti-IL-23, anti-a4-integrin, and anti-a4b7 integrin have effective activity against IBD inflammatory response. Further investigation in IBD immunology to increase the success of these treatments and to find other therapies.Microbiota in IBDThere are several hypotheses about homeostasis between microbiota, intestinal epithelia, and the immune system that is disrupted by an interaction of genetic and environmental factors, resulting in chronic inflammation. Data showed that different IBD variants are likely mediated by a change in microbiota, and this change is influenced by a certain genetic background. A good example is the decreased population of Faecalobacterium Prausnitzii and Roseburia in patients with a NOD 2 mutation.<a class="elsevierStyleCrossRef" href="#bib0420">19</a> Moreover, the dysregulation of intestinal crypts in IBD can be secondary to cells variations. The change in mucosal barrier, identified as a loss in goblet cells in IBD patients, results in a reduction of antibacterial proteins, and it is still unclear if others cell modifications underly the event triggering the disease.<a class="elsevierStyleCrossRef" href="#bib0425">20</a>Some bacteria contribute to immune responses in T cells as well as in IBD patients, affecting cytokine-cytokine receptor signalling, the interaction with epithelial cells, and the immune system. It was showed in experimental mice models that Bacteroides fragilis and capsular lipopolysaccharide A improved Th1/Th2 responses by regulating the secretion of TNF-α and IL-12, and inducing the production of Treg cells.<a class="elsevierStyleCrossRef" href="#bib0430">21</a> Other models in mice propose that several bacterial strains are NF-κB suppressors, suggesting that the microbiome is an extrinsic regulator of host immunity.<a class="elsevierStyleCrossRef" href="#bib0435">22</a> Another example is Candidatus Arhromitis, the segmented filamentous bacteria, where colonization of such bacteria promotes the maturation of the mucosal immune system preventing dysbiosis.<a class="elsevierStyleCrossRef" href="#bib0440">23</a>The composition of the microbiota is altered in patients with IBD. These findings are associated with the increase in several pathogens and overall changes in the compostion of microbiome compared to healthy controls, considering not only bacteria, but also fungi, viruses, and other organisms. Phylum firmicutes is commonly reduced in the stool of patients with Crohn's disease. Proteobacteria phylum are increased in patients with IBD compared to healthy patients.<a class="elsevierStyleCrossRef" href="#bib0440">23</a> Moreover, the biodiversity and composition of fungal microbiota is altered as well. A skewing of microbiota compared to healthy subjects was observed. There is an increase in Basidiomycota/Ascomycota, a decrease of Saccharomyces, and an increase proportion of Candida albicans compared to healthy controls.<a class="elsevierStyleCrossRef" href="#bib0405">16</a> Furthermore, metagenomics allows the analysis of viral particles isolated from samples. A change in bacteriophage composition in IBD was found, showing an increase in Caudovirales bacteriophages in ileal biopsy samples, which is correlated with a reduction in bacterial diversity.<a class="elsevierStyleCrossRef" href="#bib0445">24</a> This suggests that dysbiosis is part of the pathogenesis of IBD.It is recognized that metabolites are different between IBD patients and non-IBD controls secondary to IBD microbiome. One hundred twenty two associations between metabolic diversity and specific microbiome were identified in IBD patients. Several computation methods provide a guidance to characterize the IBD microbiome and metabolome. The different variation patterns of disease phenotypes depends on the microbial taxonomic profile of every patient.<a class="elsevierStyleCrossRef" href="#bib0355">6</a> Deep sequencing technology progressively discloses the role of dysbiosis in IBD.The role of diet in IBD and the alteration of the microbiota are at several levels and are demonstrated by an association in patients with low fibre intake and a risk of Crohn's disease caused by changes in the gut microbiota in susceptible individuals.<a class="elsevierStyleCrossRef" href="#bib0450">25</a> Increased dietary heme iron intake increases the ratio of gram-negative/gram-positive bacteria in mice.<a class="elsevierStyleCrossRef" href="#bib0455">26</a> Moreover, an increase in sulfite-reducing Bilophila wadsworthia induces colonic inflammation in mice with an IL10-knockout.<a class="elsevierStyleCrossRef" href="#bib0460">27</a> Meanwhile, a Mediterranean diet, rich in fruits, vegetables, and red wine is associated with an increased diversity of the microbiome, especially Faecalibacterium prausnitzii, which is considered bacteria with anti-inflammatory properties.<a class="elsevierStyleCrossRef" href="#bib0465">28</a>TreatmentThere are different ways in which bacteria and other microorganisms’ changes can alter composition and functions in IBD. Conventional therapy with corticosteroids, immunomodulators, and biologic therapy might help induce remission; however, there are many alternatives to treat inflammation through modifications in the microbiome environment that further ameliorate dysbiosis.<a class="elsevierStyleCrossRef" href="#bib0470">29</a> It can be divided into traditional methods, methods under development, and novel hypotheses to configure microbiome. First, in the traditional methods the use of probiotics, prebiotics, antibiotics, and combinations of these are included. Thereafter, in the methods under development there are fecal microbiota transplant (FMT) and other novel hypotheses.ProbioticsThe rationale behind probiotics is restoration of the microbial balance, modulation, mucosal protection, and induction of immune responses in IBD.<a class="elsevierStyleCrossRef" href="#bib0475">30</a> The study of probiotics in IBD has many outcomes and is broad. One meta-analysis showed a significant increase in remission rates in patients with active ulcerative colitis (p=0.01) and the rate of remission rates was significantly higher in patients with active UC treated with concomitant probiotics. The probiotic called VSL#3 showed an increased remission rate in mild-to-moderately active UC compared to controls, and a relapse reduction rate in patients with pouchitis.<a class="elsevierStyleCrossRefs" href="#bib0480">31,32</a>Another recent meta-analysis including 18 trials revealed that probiotics had different effects in terms of remission in Crohn's disease. Some studies did not find a significant influence in Crohn's disease (p=0.07); however, 3 trials in children with IBD showed the advantage of its use.<a class="elsevierStyleCrossRef" href="#bib0490">33</a> Mice models suggest that Lactobacillus plantarum CBT LP3 can be used as a potent immunomodulator with implications in IBD by decreasing intestinal permeability; however, this needs further confirmation.<a class="elsevierStyleCrossRef" href="#bib0495">34</a> No adverse effects were detected between probiotics and controls in UC treatment.<a class="elsevierStyleCrossRef" href="#bib0480">31</a> Current Cochrane studies do not favor the use of probiotics in CD; however, the last study needs an update with new information about probiotics in CD.<a class="elsevierStyleCrossRef" href="#bib0500">35</a>PrebioticsPrebiotic formulations are food substances that are not digested in the human small bowel and increase selective growth of beneficial bacteria in the colon; a benefit that has not been fully explored in IBD. The basis of providing fiber and prebiotic oligosaccharides to increase the abundance of short-chain fatty acid commensal species is as a therapeutic target with immunoregulatory properties.<a class="elsevierStyleCrossRef" href="#bib0440">23</a> The nondigestible polymers of fructose (fructo-oligosaccharides, FOS) are found naturally and fermented by bifidobacteria and lactobacilli.<a class="elsevierStyleCrossRef" href="#bib0505">36</a>In mice models, it is suggested that colitis is diminished in subjects treated with prebiotics compared to untreated controls, and an increase in the abundance of Bifidobacterium spp, and a decrease of Clostridium cluster XI and C. difficile toxin gene expression are closely related to less chronic intestinal inflammation.<a class="elsevierStyleCrossRef" href="#bib0510">37</a> Another trial in mice showed that side chains of pectin not only increased the levels of prebiotic effects but also downregulated inflammatory cytokines (IL-6).<a class="elsevierStyleCrossRef" href="#bib0515">38</a> The clinical trial with more patients (n=103) demonstrated a lack of clinical benefit in using prebiotic supplementation in active Crohn's disease; however, this warrants further investigation in maintaining remission or other unexplored areas.SynbioticProbiotic therapy can be improved by adding a prebiotic; allowing a better substrate for bacterial growth. This combination is called synbiotic. A pilot study showed that combining a probiotic like Bifidobacterium longum and a prebiotic like inulin promotes short-term active clinical UC improvement and decreases inflammatory cytokines, such as TNFα and IL1a.<a class="elsevierStyleCrossRef" href="#bib0520">39</a> Another study showed histological improvement and TNFα levels in biopsies at 3 months<a class="elsevierStyleCrossRef" href="#bib0525">40</a> and that preparations composed of six probiotic strains, and a prebiotic of FOS resulted in decreased inflammatory markers in the synbiotic group. In terms of clinical, serologic, and endoscopic activity levels a statistically significant improvement of synbiotic versus placebo was shown.<a class="elsevierStyleCrossRef" href="#bib0530">41</a>Newer data showed that a combination of Lactobacillus probiotics and prebiotics had a significant effect in remission only in patients with UC (p=0.03) and combination with Saccharomyces boulardii, Lactobacillus, and VSL#3 probiotics in CD could be potentially worthy.<a class="elsevierStyleCrossRef" href="#bib0490">33</a> However, information regarding synbiotic studies has a low number of patients and this precludes making assumptions.AntibioticsDysbiosis is an important cause of pathogenesis in IBD and its alteration with the use of antibiotics is a potential therapy; however, based on several studies, antibiotics play a role in the development of IBD by leading to dysbiosis and reducing bacterial diversity.<a class="elsevierStyleCrossRef" href="#bib0535">42</a> There is an upward trend of data in favor of antibiotic use for IBD flare-ups, and no association exists between the use of antibiotics and the development of IBD in early stages of life.<a class="elsevierStyleCrossRef" href="#bib0540">43</a>Regarding active UC, data from meta-analyses suggest that antibiotic use maintain remission in 64% compared to placebo, 48%, favoring its use in UC.<a class="elsevierStyleCrossRef" href="#bib0545">44</a> However, the heterogeneity among studies showed that intravenous antibiotics in the long-term are not helpful in UC activity. Some other studies demonstrate that either antibiotic monotherapy or combinations help to achieve better clinical and endoscopic outcomes at 6 and 12 months.<a class="elsevierStyleCrossRef" href="#bib0550">45</a>In CD, antibiotics are used in treating primary active disease in luminal disease, fistulizing disease, and septic complications such as abscesses or post-operative infections. Information from meta-analyses and Cochrane data suggest that either luminal antibiotics or other type of antibiotics have a modest benefit against active CD and may not be clinically meaningful in the short-term or as maintenance of remission with a clinical endpoint at 52 weeks.<a class="elsevierStyleCrossRef" href="#bib0555">46</a> Moreover, the benefit of using antibiotics with immunomodulators or anti-TNF therapy in CD has little benefit in patients at high risk for recurrence, with weak supporting evidence and a need for further evaluation.<a class="elsevierStyleCrossRef" href="#bib0560">47</a>The use of antibiotics in pouchitis, acute or chronic, has different managements depending on data. A meta-analysis shows that antibiotics induce remission with a rate of 74% in chronic pouchitis (95% CI: 56–93%, p<0.001). Another meta-analysis that included prevention and treatment of pouchitis showed good effectiveness of ciprofloxacin in acute and chronic pouchitis; however, with a low effectiveness of metronidazole. Furthermore, current data in terms of pouchitis prevention is inconclusive, powered studies are needed to determine its effectiveness.<a class="elsevierStyleCrossRef" href="#bib0565">48</a> In chronic pouchitis, antibiotic use promotes microbiome-associated resistant strains. This suggests that new schemes of antibiotic therapy and short-term antibiotic alternation should be used.<a class="elsevierStyleCrossRef" href="#bib0570">49</a>Fecal microbiota transplantation (FMT)Fecal microbiota transplantation is a process in which a fecal suspension from a healthy individual is transferred to a recipient. This process was originally designed as part of the treatment of refractory Clostridiodes difficile; however, there is robust information about its use in IBD including 9 meta-analyses, 4 RCT, and many cohort studies (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The information among meta-analyses is heterogeneous due to the information included and the outcomes reviewed. Induction of remission of active UC with FMT was significantly more effective than placebo in the four published RCT with 28% in the FMT group versus 9% in placebo groups (p=0.64, I2=0%). The latest meta-analysis including 4 RCT and 23 cohort studies, 21% of patient achieved clinical remission (CR) with a high risk of heterogeneity. FMT was associated with clinical improvement and endoscopic remission.<a class="elsevierStyleCrossRefs" href="#bib0575">50,51</a> Moreover, FMT is associated with a significant increase in the mucosal gut of immunoregulatory cells and anti-inflammatory metabolism (increase of butanoate) and a reduction of Th17 proinflammatory pathways.<a class="elsevierStyleCrossRef" href="#bib0585">52</a>The first meta-analysis regarding the success of CD in CR showed a pooled estimate of 60.5% (p=0.05; I2=37%); however, a more recent meta-analysis showed a pooled portion of CR of 30% (p<0.01, I2=75%) with moderate heterogeneity and lower than previous data.<a class="elsevierStyleCrossRefs" href="#bib0575">50,53</a> The main limitation among studies with CD and FMT is the poor correlation between clinical and endoscopic outcomes and the lack of data in this topic due the low prevalence of CD; most information is from cohort studies and case reports.When IBD patients are divided into subgroups according to disease severity, information shows that patients with moderate-severe disease from cohort studies could achieve more CR than those with mild-moderate disease; however, in RCT, all patients included had mild-moderate disease severity.<a class="elsevierStyleCrossRef" href="#bib0575">50</a>One of the most important characteristics of FMT is its safety. Common adverse events related to patients treated with FMT included gastrointestinal system diarrhea (13%), abdominal distention/flatulence (11.6%), nausea/vomiting (6.1%), abdominal pain (5.5%) and others. Most of the complications like fever, sore throat, and gastrointestinal complaints were self-limiting lasting 24h. The reports of death and worse outcomes are scarce in the current information.<a class="elsevierStyleCrossRefs" href="#bib0580">51,54</a>In terms of preparation of the sample for FMT according to current information, the FMT donor is predominantly a man less than 30-years-old. This could be explained by the higher prevalence of irritable bowel syndrome in women. There is still controversy about the perfect stool donor; in available data, a close relative or friend was chosen. A recent study indicates the importance of matching donors and patients for long-term maintenance of UC; siblings’ relationship has a significantly higher maintenance rate compared with a parent-child relationship.<a class="elsevierStyleCrossRef" href="#bib0600">55</a> Information using mice models suggests a core transferable microbiota is necessary in responders to faecal microbiota transplant in UC to trigger an adequate immune reaction.<a class="elsevierStyleCrossRef" href="#bib0605">56</a> No significant difference exists between using a frozen-stool FMT compared to fresh stool or the delivery route used (either common upper GI or common lower GI) in UC or CD.<a class="elsevierStyleCrossRef" href="#bib0575">50</a> Furthermore, from 338 clinical trials regarding FMT, only 10 studies had the characteristics of FMT therapy in IBD patients. In <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> are included the current studies from clinicals about FMT and IBD research. However, more data is needed in RCT and prospective studies to evaluate specific donors’ microbiome characteristics, the diet that FMT donors are eating due to its relevancy in the outcome of this treatment, and specific therapies used in transplanted patients such as mesalazine or biologic because these data are important considerations for future research.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Areas under research: synthetic mixtures of microbesLive biotherapeutic products (LBPs) are a mixture of protective commensal bacteria that modulate inflammation through several levels including interaction with inflammosome and tolerogenic responses. SER-109, a mixture of bacterial spores from 50 bacterial species from healthy donors’ fecal matter shows promise to regulate immune responses and several other trials are underway.<a class="elsevierStyleCrossRef" href="#bib0610">57</a> Furthermore, the precise edition of microbiota composition can ameliorate adverse effects of dysbiosis. Investigational microbe-based immunotherapy called QBECO, formulated from inactivated strains of a gut pathogen showed objective reduction of UC disease pathology by activation of the immune system.<a class="elsevierStyleCrossRef" href="#bib0615">58</a> Other experimental studies in mice showed that the addition of tungstate-mediated microbiota reduced severity of intestinal inflammation.<a class="elsevierStyleCrossRef" href="#bib0620">59</a>ConclusionThe last decades show a trend toward an increase in IBD and the role of the microbiome in its development and pathogenesis. Several hypotheses about dysbiosis and immuno-regulation correlate with the phenotype of IBD. Many therapies beside the use of steroids, immunomodulators or biologic therapy are still in a constant investigational process. Hereby, several options for the treatment of IBD to ameliorate dysbiosis were included; some of them have been fully studied but others are under development. The role of novel therapies, such as FMT and precision medicine, is growing and further evaluation of these therapies is needed. There are some characteristics of the FMT donors that should be controlled more in future studies such as a donors’ diet in order to assess all possible variables that limit FMT efficacy. According to the knowledge in microbiome pathophysiology in IBD, the study of the microbiome population should be included in all the future RCTs regarding this topic. Limitations in Its current study includes the multifactorial pathophysiology of IBD, a lack of evidence in certain modalities of treatment, and some of the data used are based on experimental models and still need validation on clinical grounds.FundingNone.Conflicts of interestsNone." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1779218" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1562076" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1779217" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1562077" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:12 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Search strategies" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Data collection and quality assessment of studies" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Normal immune regulation" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Microbiota in immune-regulation" ] 4 => array:3 [ "identificador" => "sec0035" "titulo" => "Pathogenesis in IBD" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Immune-regulation in IBD" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Microbiota in IBD" ] ] ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Treatment" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Probiotics" ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Prebiotics" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Synbiotic" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Antibiotics" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Fecal microbiota transplantation (FMT)" ] 11 => array:2 [ "identificador" => "sec0080" "titulo" => "Areas under research: synthetic mixtures of microbes" ] ] ] 6 => array:2 [ "identificador" => "sec0085" "titulo" => "Conclusion" ] 7 => array:2 [ "identificador" => "sec0090" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflicts of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-06-21" "fechaAceptado" => "2021-08-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1562076" "palabras" => array:4 [ 0 => "Inflammatory bowel disease" 1 => "Microbiome" 2 => "Microbiota" 3 => "Microbiota transplantation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1562077" "palabras" => array:4 [ 0 => "Enfermedad inflamatoria intestinal" 1 => "Microbioma" 2 => "Microbiota" 3 => "Trasplante microbiota" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The incidence of inflammatory bowel disease (IBD) is increasing. Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations. We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation, and therapies that can modify microbiota. A comprehensive systematic literature search was performed through April 2020 in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov. Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD. This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation, immune pathophysiology of IBD, and shows the evidence of several therapeutic targets to change microbiome in patients with IBD, such as prebiotics, probiotics, antibiotics, fecal microbiota transplant, and others." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La incidencia en enfermedad inflamatoria intestinal (EII) va en aumento. El microbioma es uno de los factores más importantes en su desarrollo y afecta los diferentes escenarios clínicos en pacientes con EII dependiendo de su composición y diferentes alteraciones. Se realizó una revisión sistemática para discutir la asociación entre el microbioma y EII relacionado con inmunorregulación y las terapias que pueden modificar la microbiota. Se realizó una búsqueda en la literatura hasta abril de 2020 en Pubmed, Web of Science, Cochrane library y clinicaltrials.gov. La inclusión del material requiere EII, inmunorregulación y las terapias alternativas para EII. Este estudio ayuda a explicar el origen multifactorial de la diversidad del microbioma incluyendo la inmunorregulación normal, fisiopatología inmuno de EII y muestra la evidencia de diferentes blancos terapéuticos para cambiar el microbioma en pacientes con EII como prebióticos, probióticos, antibióticos, trasplante de materia fecal, entre otros." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "RCT, randomized control trial; UC, ulcerative colitis; CD, Crohn's disease; CR, clinical remission; NR, not registered." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author/year \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Studies \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study of donors’ microbiome \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study of donors’ diet \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disease activity \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FMT route \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcome \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adverse effects \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Colman et al./2014<a class="elsevierStyleCrossRef" href="#bib0590">53</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 cohort studies+8 case studies+1 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">122 patients79 UC; 39 CD, 4 IBD unclassified \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23% mild/moderate13% moderate–severe16% severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refractory therapy 8%Active disease 44%Refractory pouchitis 4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Single NJ tube/Colonoscoppy/Daily enemas/Gastroscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Overall CR 45%UC CR 22%(95% CI 10.4–40.8, I2=0%)CD CR60% (95% CI 28.4–85.6, p=0–05, I2=37%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fever, abdominal tenderness, diarrhea \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shi et al./2016<a class="elsevierStyleCrossRef" href="#bib0625">60</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 cohort studies+8 case studies+2 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">234 UC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enema/Colonoscopy/Gastroscopy/Nasogastric tube/Nasoduodenal tube/Endoscopic cecostomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Overall CR 41.58% (95% CI 24.7–58.7, I2=36.5%)65.2% Clinical response (95% CI 43.7–83, I2=40.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fever, diarrhea, bloating, worsening colitis, urgent colectomy (placebo), rectal abscess, perforation, CMV, cervix carcinoma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sun et al./2016<a class="elsevierStyleCrossRef" href="#bib0630">61</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 cohort studies+1 case–control +2 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">133 UCAdults +Children \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Endoscopic scores \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enema/NJ/Colonoscopy/Gastroscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UC CR 30.4 (95%, CI 22.6–30.4, I2=33%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fever, diarrhea, abdominal cramping \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Costello et al./2017<a class="elsevierStyleCrossRef" href="#bib0635">62</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 cohort studies+4 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">168 UC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild–moderate majority of patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nasogastric/NJ/endoscopic duodenal, enema, colonoscopy or rectal tube \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UC CR 28% (95% CI 1.82–7.39, p>0.01, I2=0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worsening colitis, small intestine CD, gastrointestinal complaints \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Paramsothy et al./2017<a class="elsevierStyleCrossRef" href="#bib0640">63</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 cohort studies+14 case studies+4 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">661 patients,555 UC; 83 CD; 23 CD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53% mild/moderate12% moderate/severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.4% active disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nasogastric/Gastroscopy/Colonoscopy/Enema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UC CR 33% (95% CI 23–43, p=001, I2=54%), CD CR 52% (95% CI=40–64, p=001, I2=58%), pouchitis CR 21.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bloating, diarrhea, flatulence, abdominal pain, borborygmus, fever \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Narula et al./2017<a class="elsevierStyleCrossRef" href="#bib0645">64</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">277 UC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% mild/moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nasoduodenal/Colonoscopy/Enema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UC CR 42.1% (95% CI 3–17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No statistical difference in adverse effects \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cao et al./2018<a class="elsevierStyleCrossRef" href="#bib0650">65</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 cohort studies+4 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">446 UC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RCT 100%mild/moderateCohortsNR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nasogastric/NJ/endoscopic duodenal, enema, colonoscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UC CR 28.9 (p0.59, I2=0%)Clinical response 46.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fang et al./2018<a class="elsevierStyleCrossRef" href="#bib0575">50</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 cohort studies+4 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">459 patientsUC 365CD 94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RCT100% mild/moderateCohort studies28% mild/moderate12% moderate/severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.5%Refractory7.8% Active disease6.9% Hormone dependent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nasogastric/NJ/endoscopic duodenal, enema, colonoscopy or rectal tube \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Overall CR 28.8%UC CR 21% (95% CI: 8–37)CD CR 30% (95% CI: 10–48)Clinical response 53% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diarrhea, abdominal pain, borborygmus, fever, urtircaria, kidney stones. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imdad et al./2018<a class="elsevierStyleCrossRef" href="#bib0580">51</a> Cochrane Library \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">277 UC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RCT100% mild/moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nasoduodenal/Colonoscopy/Enema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 weeks CR 37% (95% CI: 1.07–3.86, I2=50%)Clinical response 49% (95% CI 0.98–2.95, I2=50%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No serious adverse events between groups \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "FMT for IBD reviews and meta-analysis." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn's disease; CDI, Clostridium difficile infection; FMT, fecal microbiota transplant **Information extracted from clinicaltrials.gov." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Title \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Status \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study results \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Conditions \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Interventions \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fecal Microbiota Transplantation in Pediatric Patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Completed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IBDCDUC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase 1:FMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=5025 CD25 UC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Failing primary therapy or in a flare. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Standardized Fecal Microbiota Transplantation for Inflammatory Bowel Disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown status \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results Available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IBDCDUC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase 2:FMTDrug: Mesalazine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=4020 CD20 UC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Efficiency, durability and safety of standardized FMT for IBD treatment. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Efficacy of Fecal Microbiota Transplantation for Inflammatory Bowel Disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recruiting \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UCCDConstipation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase 3:FMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Efficiency and safety of FMT in a series of 80 patients with moderate to severe UC and CD. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fecal Microbiota Transplantation for Health Improvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enrolling by invitation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UCIBSCD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase: NAFMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Select donors of fecal samples for carrying out the procedure of fecal transplantation of microbiota \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FMT in inflammatory bowel disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recruiting \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FMTCDUCMicroscopic colitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CohortFMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Evaluating the use of faecal microbiota transplantation amongst patients with Inflammatory Bowel Disease and Microscopic Colitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ICON-2 FMT and Bezlotoxumab Compared to FMT and Placebo for Patients With IBD and CDI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recruiting \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IBDCDI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase2:Drug: BezlotoxumabDrug: PlaceboDrug: FMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=120 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical and microbiological impacts of FMT in combination with Bezlotoxumab (bezlo) compared to FMT in combination with placebo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fecal Transplantation for Inflammatory Bowel Disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Terminated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IBD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase 1:FMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FMT improvement for colitis in IBD patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Manipulating the microbiome in IBD by antibiotics and FMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Active, not recruiting \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UC exacerbation, severe activityCrohn's colitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase 4:Drug: antibioticsDrug: corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Assess the outcome of FMT in those not responding to five days of therapy with antibiotics or corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fecal Microbiota Transplant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Active, not recruiting \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No results available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CDIIBDCDUC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase: NAFMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Determine the effect of FMT on the gut microbiota through the use of 454 pyrosequencing before and after transplantation in these patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bacteriotherapy in pediatric inflammatory bowel disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Completed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Has results \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IBDCDUC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase 1:FMT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N=13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Learn whether this experimental therapy delays the need for starting additional medications to treat pediatric IBD. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Current ongoing clinical trials for FMT in IBD." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:65 [ 0 => array:3 [ "identificador" => "bib0330" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changing global epidemiology of inflammatory bowel diseases—sustaining healthcare delivery into the 21st century" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.N. 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Inflammatory bowel disease: The role of commensal microbiome in immune regulation

Enfermedad inflamatoria intestinal: el rol de microbioma comensal en la regulación inmune

Martín Ivan Wah-Suáreza, Manuel Alejandro Martínez Vázquezb, Francisco Javier Bosques-Padillac,

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fbosques58@hotmail.com

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a Hospital Universitario Monterrey, Mexico

b Tecnologico de Monterrey: Instituto Tecnologico y de Estudios Superiores de Monterrey, Mexico

c División de Gastroenterología y Hepatología, Hospital Universitario “Dr. José E. González”, Monterrey, NL, Mexico

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      0 => array:4 [
        "autoresLista" => "Mart&#237;n Ivan Wah-Su&#225;rez, Manuel Alejandro Mart&#237;nez V&#225;zquez, Francisco Javier Bosques-Padilla"
        "autores" => array:3 [
          0 => array:3 [
            "nombre" => "Mart&#237;n Ivan"
            "apellidos" => "Wah-Su&#225;rez"
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          1 => array:3 [
            "nombre" => "Manuel Alejandro Mart&#237;nez"
            "apellidos" => "V&#225;zquez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
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          2 => array:4 [
            "nombre" => "Francisco Javier"
            "apellidos" => "Bosques-Padilla"
            "email" => array:1 [
              0 => "fbosques58@hotmail.com"
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            "referencia" => array:2 [
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                "identificador" => "aff0015"
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                "identificador" => "cor0005"
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            "entidad" => "Hospital Universitario Monterrey&#44; Mexico"
            "etiqueta" => "a"
            "identificador" => "aff0005"
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          1 => array:3 [
            "entidad" => "Tecnologico de Monterrey&#58; Instituto Tecnologico y de Estudios Superiores de Monterrey&#44; Mexico"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Divisi&#243;n de Gastroenterolog&#237;a y Hepatolog&#237;a&#44; Hospital Universitario &#8220;Dr&#46; Jos&#233; E&#46; Gonz&#225;lez&#8221;&#44; Monterrey&#44; NL&#44; Mexico"
            "etiqueta" => "c"
            "identificador" => "aff0015"
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            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
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    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Enfermedad inflamatoria intestinal&#58; el rol de microbioma comensal en la regulaci&#243;n inmune"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Inflammatory bowel disease &#40;IBD&#41; epidemiology has changed over time&#46; There is an increase in prevalence and incidence in many countries&#46; The reports of IBD epidemiology models forecasts that IBD prevalence will increase by 3&#37; per year&#44; rising in prevalence from 0&#46;7&#37; in 2018 to 1&#37; by 2030&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">1</span></a> IBD epidemiology is heterogeneous among different countries&#59; however&#44; regions with a lower prevalence such as Latin America&#44; have had an increased incidence in the last decades&#44; as in Brazil and Mexico&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">2&#44;3</span></a> Therefore&#44; it is burdensome to establish an accurate incidence or prevalence in IBD worldwide but there is a trend toward an increase&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The changes in incidence have not been fully explained&#46; IBD is recognized as a multifactorial disease that can affect the small or large intestine in many different ways&#46; It is still difficult to establish a relationship of causality&#59; however&#44; there is enough rationale to presume that the synergy among environmental&#44; genetic&#44; and compositional changes in intestinal microbiome could predispose the development of IBD&#46; Multiple environmental determinants&#44; such as antibiotic use&#44; breastfeeding&#44; air pollution and other urban conditions&#44; influence the risk of developing IBD and can alter the natural history of IBD from perinatal development to adulthood&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">4</span></a> In terms of genetics&#44; genetic and epigenetic changes were found in IBD that can trigger different disease phenotypes&#59; e&#46;g&#46;&#44; severity and cancer propensity&#46; This precision medicine information requires more aggressive surveillance and treatment in patients&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">5</span></a> Moreover&#44; there is an association between an altered microbiome in IBD called dysbiosis&#44; which results in a different metagenomic and metabolomic profile&#44; and different concentrations of metabolic compounds in feces&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The purpose of this review is to summarize the current association between commensal microbiome and immune regulation in healthy individuals and IBD patients&#44; and discuss the potential treatments related to modifications in the microbiome in human IBD&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Search strategies</span><p id="par0020" class="elsevierStylePara elsevierViewall">We searched for articles published in PubMed&#44; Web of Science&#44; the Cochrane Library&#44; and clinicaltrials&#46;gov with the following MeSH terms for IBD and commensal bacteria&#58; &#8220;Microbiota&#8221;&#44; &#8220;Commensal&#8221;&#44; &#8220;Dysbiosis&#8221;&#44; &#8220;IBD&#8221;&#44; &#8220;Ulcerative colitis&#8221;&#44; &#8220;Crohn&#39;s disease&#8221;&#44; &#8220;Gastrointestinal immune&#8221;&#46; Then&#44; the results were combined using &#8220;AND&#8221; with studies identified by other keywords such as &#8220;Ulcerative colitis&#8221;&#44; &#8220;Crohn&#39;s disease&#8221;&#44; &#8220;Prebiotics&#8221;&#44; &#8220;Probiotics&#8221;&#44; &#8220;Antibiotics&#8221;&#44; &#8220;Faecal microbiota transplant&#8221;&#44; &#8220;IBD therapy&#8221;&#44; &#8220;Meta-analysis&#8221;&#46; We enrolled all relevant data up to April 2020 by reviewing the titles and abstracts&#46; The reference lists of relevant articles were also scrutinized&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Data collection and quality assessment of studies</span><p id="par0025" class="elsevierStylePara elsevierViewall">The methodological quality of the current study includes case reports&#44; cohort studies&#44; random clinical trials &#40;RCTs&#41; and reviews and meta-analysis&#46; The risk of bias in the information included depends on the level of evidence according to the type of study&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Normal immune regulation</span><p id="par0030" class="elsevierStylePara elsevierViewall">The immunologic system is composed of innate and adaptative responses&#46; In the latter are the classical Th1 and Th2 immune response theory where different production of cytokines with interferon-&#947; &#40;IFN-&#947;&#41; for Th1 cells to attack intracellular organisms and interleukin &#40;IL&#41;-4&#44; IL-5&#44; and IL-13 for Th2 cells for parasitic infections&#46; Another immunologic pathway with Th17 cells can raise IFN-&#947; effects that are similar to Th1 response&#44; but also target innate immunity through neutrophil activity and epithelial cells response&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">7</span></a> The cytokine IL-23&#44; an important component in the cascade of Th17 cells acts as an effector of T cell subsets and it is involved in many responses that cause inflammation&#46; CD4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Th17 are not found in the germ-free mouse intestines&#44; showing that are generated according to microbiota and external stimuli&#46; Some reports indicated that Il17A deficient mice caused increased colitis associated to high levels of IFN-&#947; due to the lack of inhibition of Th1 cells pathway&#46; After all the subsets of T cells are in a steady sate&#44; antigen presentation cells favor development of regulatory T cells &#40;Tregs&#41; that act to suppress inflammation by suppressing effector T cells&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Intestinal epithelial cells &#40;IECs&#41; and mesenchymal are important as barrier function and host response to infection and tissue damage as well&#46; IECs are not only a barrier but also the beginning of the innate immune response to tissue damage&#59; the balance of immune response is between NF-&#954;B and STAT3 signaling pathways&#46; Different cytokines induce activation&#44; proliferation and inflammation-driven repair pathways in IECs including IL-6&#44; IL-11&#44; and IL-22 through STAT3 signals stimulation&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">9</span></a> The mesenchymal cells underlying IECs in another important component in immune system&#46; NOD2 activation through mesenchymal cells protects against enteric pathogens&#44; and provides differentiation factors for IECs stems cells for repair&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Microbiota in immune-regulation</span><p id="par0040" class="elsevierStylePara elsevierViewall">The gastrointestinal tract has an enriched number of microorganisms that interact with the immune system to produce certain types of signals depending on the entity involved&#46; Different bacteria harbored in the intestine are well tolerated by the immune system because of the host genetic code or a response induced by bacteria&#59; this process is called tolerogenic response&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">11</span></a> The signal between the microbe and the host is reciprocal at several levels and is interconnected by a mutual regulation of development and homeostasis&#46; The detection of disarrays in the components that are related in this interaction between microorganisms and intestinal environment is responsible for a cascade that triggers an inflammatory process&#46; This inflammatory process ends in the abrupt increment of frequency of oncologic&#44; liver&#44; and inmmunoallergic processes&#44; including IBD&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">12</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The microbiome is not constant during the lifespan and changes with age&#46; Every segment of the gastrointestinal tract influences the concentration and type of microbiome&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">13</span></a> Microbiota diversity depends on diet as well&#46; The type of diet influences the plasticity of microorganisms living in the gastrointestinal tract&#46; A diet rich in animal products enhances bile tolerant bacteria &#40;<span class="elsevierStyleItalic">Alistipes</span>&#44; <span class="elsevierStyleItalic">Bilophila</span>&#44; and <span class="elsevierStyleItalic">Bacteroides</span>&#41; and depletes others that metabolize plants&#44; such as Firmicutes&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">14</span></a> The growth dynamics of microbiota is very diverse and includes all kingdoms of organisms&#44; such as prokaryotes&#44; eukaryotes and viruses&#46; The introduction of specialized databases with metagenomics has consistently allowed the classification of more than 30 prokaryotic phyla&#44; finding human eukaryotic microbiome as pathogens&#44; commensals and beneficial organisms&#44; and identifying bacteriophages that keeps the gut in healthy homeostasis&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">13</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The role of different organisms as pathogenic or commensal is still an area of study&#46; Some studies showed specific bacteria that help in several ways in mucin production&#44; such as <span class="elsevierStyleItalic">Akkermansia</span><span class="elsevierStyleItalic">muciniphila</span> which changes mucus characteristics that improves barrier function and affects homeostasis&#46; Commensals&#44; such as <span class="elsevierStyleItalic">Faecalibacterium prausnitzii</span> needs an environment enriched with mucin to colonize the intestine&#46; Furthermore&#44; different bacteria byproducts like butyrate&#44; boosts the growth of commensal bacteria&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">15</span></a> Likewise&#44; a few fungal microbiota are considered mycobiota in the gastrointestinal tract&#59; this includes <span class="elsevierStyleItalic">Candida&#44; Saccharomyces&#44; Penicillium&#44;</span> and <span class="elsevierStyleItalic">Aspergillus</span>&#59; however some data argue against fungal colonization and suggest that fungi are not common colonization flora&#46; It is debated whether the fungal microbiota is able to colonize as commensals&#44; like bacteria&#44; or is external contamination from the mouth or diet&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">16</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The progress of genetic profiling&#44; including proteomics&#44; metagenomics&#44; and metabolomics&#44; has contributed to the discovery of the composition of complex microbial communities of not only bacteria&#44; but also many other microorganisms&#46; This can help elucidate the change in microbiota as a cause of diseases&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pathogenesis in IBD</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Immune-regulation in IBD</span><p id="par0060" class="elsevierStylePara elsevierViewall">IBD is involved in the whole process of immune regulation including innate and adaptative mechanisms&#46; The disease pathogenesis is multifactorial and complex through different immune abnormalities&#46; Innate immunity involving neutrophils&#44; monocytes&#44; and macrophags respond to invading bacteria&#46; These cells accumulate in inflamed intestines in UC and CD in the form of neutrophil-enriched crypt abscesses and granulomas&#44; respectively&#46; NOD2&#44; which is the strongest predictor of CD&#44; is associated with defects in innate immunity&#46; Furthermore&#44; TGF-&#946; is another regulator of intestinal inflammation which is impaired by the inhibition with molecules like SMAD 7&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Dysfunctional Tregs activity&#44; disrupt T and B cell activation and decreased innate immune system are implicated in auto-inflammatory responses&#46; Th1&#44; Th2&#44; and Th17 cells subsets are arranged in different levels of the pathogenesis of IBD&#46; The main signaling defects that lead to infantile IBD are IL-10 signaling&#46; IL-10 has an important role in intestinal homeostasis&#44; mice with IL-10 knock out develop colitis&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">10</span></a> It is controversial the exact mechanism of Th17 cells in the pathogenesis of CD&#44; however populations of CD4 T cells with CCR6&#43;&#44; IL-23R&#43;&#44; and CD 161&#43; are present in patients with IBD lesions&#46; CD is associated with defects in autophagy&#44; bacterial sensing&#44; and excessive Th17 pathway activation&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">17</span></a> In UC&#44; genetic studies linked IL23 receptor and Th17 pathway to immune responses&#46; IL-23 promotes survival of Th17 cells during inflammatory response&#59; it increases cytokines such as granulocyte-macrophage colon stimulating factor and IFN-&#947; and inhibits intestinal Tregs cells response&#46; Another cytokine is IL-13 which excessive production is implicated in pathogenesis by the natural killer T cells&#44; defects in epithelial barrier integrity and excessive Th17 pathway activation&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">7</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Mesenchymal cells are involved in the pathogenesis of IBD and have implications in its treatment&#46; IL-6 family cytokine Oncostatin M &#40;OSM&#41; and its receptor are increased in active CD and UC&#46; Moreover&#44; inflammatory monocytes and inflammation-associated fibroblasts &#40;IAFs&#41; are augmented in inflamed tissue of IBD patients&#46; These types of cells intervene in medication resistance through OSM and its receptor pathways&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">10&#44;18</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Different recognized targets such as IL-1 receptor&#44; anti-TNF&#44; anti-IL-23&#44; anti-a4-integrin&#44; and anti-a4b7 integrin have effective activity against IBD inflammatory response&#46; Further investigation in IBD immunology to increase the success of these treatments and to find other therapies&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Microbiota in IBD</span><p id="par0080" class="elsevierStylePara elsevierViewall">There are several hypotheses about homeostasis between microbiota&#44; intestinal epithelia&#44; and the immune system that is disrupted by an interaction of genetic and environmental factors&#44; resulting in chronic inflammation&#46; Data showed that different IBD variants are likely mediated by a change in microbiota&#44; and this change is influenced by a certain genetic background&#46; A good example is the decreased population of <span class="elsevierStyleItalic">Faecalobacterium Prausnitzii</span> and <span class="elsevierStyleItalic">Roseburia</span> in patients with a NOD 2 mutation&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">19</span></a> Moreover&#44; the dysregulation of intestinal crypts in IBD can be secondary to cells variations&#46; The change in mucosal barrier&#44; identified as a loss in goblet cells in IBD patients&#44; results in a reduction of antibacterial proteins&#44; and it is still unclear if others cell modifications underly the event triggering the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">20</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Some bacteria contribute to immune responses in T cells as well as in IBD patients&#44; affecting cytokine-cytokine receptor signalling&#44; the interaction with epithelial cells&#44; and the immune system&#46; It was showed in experimental mice models that <span class="elsevierStyleItalic">Bacteroides fragilis</span> and capsular lipopolysaccharide A improved Th1&#47;Th2 responses by regulating the secretion of TNF-&#945; and IL-12&#44; and inducing the production of Treg cells&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">21</span></a> Other models in mice propose that several bacterial strains are NF-&#954;B suppressors&#44; suggesting that the microbiome is an extrinsic regulator of host immunity&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">22</span></a> Another example is <span class="elsevierStyleItalic">Candidatus Arhromitis</span>&#44; the segmented filamentous bacteria&#44; where colonization of such bacteria promotes the maturation of the mucosal immune system preventing dysbiosis&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">23</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The composition of the microbiota is altered in patients with IBD&#46; These findings are associated with the increase in several pathogens and overall changes in the compostion of microbiome compared to healthy controls&#44; considering not only bacteria&#44; but also fungi&#44; viruses&#44; and other organisms&#46; <span class="elsevierStyleItalic">Phylum firmicutes</span> is commonly reduced in the stool of patients with Crohn&#39;s disease&#46; Proteobacteria phylum are increased in patients with IBD compared to healthy patients&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">23</span></a> Moreover&#44; the biodiversity and composition of fungal microbiota is altered as well&#46; A skewing of microbiota compared to healthy subjects was observed&#46; There is an increase in <span class="elsevierStyleItalic">Basidiomycota&#47;Ascomycota</span>&#44; a decrease of <span class="elsevierStyleItalic">Saccharomyces</span>&#44; and an increase proportion of <span class="elsevierStyleItalic">Candida albicans</span> compared to healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">16</span></a> Furthermore&#44; metagenomics allows the analysis of viral particles isolated from samples&#46; A change in bacteriophage composition in IBD was found&#44; showing an increase in Caudovirales bacteriophages in ileal biopsy samples&#44; which is correlated with a reduction in bacterial diversity&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">24</span></a> This suggests that dysbiosis is part of the pathogenesis of IBD&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">It is recognized that metabolites are different between IBD patients and non-IBD controls secondary to IBD microbiome&#46; One hundred twenty two associations between metabolic diversity and specific microbiome were identified in IBD patients&#46; Several computation methods provide a guidance to characterize the IBD microbiome and metabolome&#46; The different variation patterns of disease phenotypes depends on the microbial taxonomic profile of every patient&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">6</span></a> Deep sequencing technology progressively discloses the role of dysbiosis in IBD&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The role of diet in IBD and the alteration of the microbiota are at several levels and are demonstrated by an association in patients with low fibre intake and a risk of Crohn&#39;s disease caused by changes in the gut microbiota in susceptible individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">25</span></a> Increased dietary heme iron intake increases the ratio of gram-negative&#47;gram-positive bacteria in mice&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">26</span></a> Moreover&#44; an increase in sulfite-reducing <span class="elsevierStyleItalic">Bilophila wadsworthia</span> induces colonic inflammation in mice with an IL10-knockout&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">27</span></a> Meanwhile&#44; a Mediterranean diet&#44; rich in fruits&#44; vegetables&#44; and red wine is associated with an increased diversity of the microbiome&#44; especially <span class="elsevierStyleItalic">Faecalibacterium prausnitzii</span>&#44; which is considered bacteria with anti-inflammatory properties&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">28</span></a></p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Treatment</span><p id="par0105" class="elsevierStylePara elsevierViewall">There are different ways in which bacteria and other microorganisms&#8217; changes can alter composition and functions in IBD&#46; Conventional therapy with corticosteroids&#44; immunomodulators&#44; and biologic therapy might help induce remission&#59; however&#44; there are many alternatives to treat inflammation through modifications in the microbiome environment that further ameliorate dysbiosis&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">29</span></a> It can be divided into traditional methods&#44; methods under development&#44; and novel hypotheses to configure microbiome&#46; First&#44; in the traditional methods the use of probiotics&#44; prebiotics&#44; antibiotics&#44; and combinations of these are included&#46; Thereafter&#44; in the methods under development there are fecal microbiota transplant &#40;FMT&#41; and other novel hypotheses&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Probiotics</span><p id="par0110" class="elsevierStylePara elsevierViewall">The rationale behind probiotics is restoration of the microbial balance&#44; modulation&#44; mucosal protection&#44; and induction of immune responses in IBD&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">30</span></a> The study of probiotics in IBD has many outcomes and is broad&#46; One meta-analysis showed a significant increase in remission rates in patients with active ulcerative colitis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and the rate of remission rates was significantly higher in patients with active UC treated with concomitant probiotics&#46; The probiotic called <span class="elsevierStyleItalic">VSL&#35;3</span> showed an increased remission rate in mild-to-moderately active UC compared to controls&#44; and a relapse reduction rate in patients with pouchitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">31&#44;32</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Another recent meta-analysis including 18 trials revealed that probiotics had different effects in terms of remission in Crohn&#39;s disease&#46; Some studies did not find a significant influence in Crohn&#39;s disease &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;07&#41;&#59; however&#44; 3 trials in children with IBD showed the advantage of its use&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">33</span></a> Mice models suggest that <span class="elsevierStyleItalic">Lactobacillus plantarum</span> CBT LP3 can be used as a potent immunomodulator with implications in IBD by decreasing intestinal permeability&#59; however&#44; this needs further confirmation&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">34</span></a> No adverse effects were detected between probiotics and controls in UC treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">31</span></a> Current Cochrane studies do not favor the use of probiotics in CD&#59; however&#44; the last study needs an update with new information about probiotics in CD&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Prebiotics</span><p id="par0120" class="elsevierStylePara elsevierViewall">Prebiotic formulations are food substances that are not digested in the human small bowel and increase selective growth of beneficial bacteria in the colon&#59; a benefit that has not been fully explored in IBD&#46; The basis of providing fiber and prebiotic oligosaccharides to increase the abundance of short-chain fatty acid commensal species is as a therapeutic target with immunoregulatory properties&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">23</span></a> The nondigestible polymers of fructose &#40;fructo-oligosaccharides&#44; FOS&#41; are found naturally and fermented by bifidobacteria and lactobacilli&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">36</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In mice models&#44; it is suggested that colitis is diminished in subjects treated with prebiotics compared to untreated controls&#44; and an increase in the abundance of <span class="elsevierStyleItalic">Bifidobacterium</span> spp&#44; and a decrease of <span class="elsevierStyleItalic">Clostridium</span> cluster XI and <span class="elsevierStyleItalic">C&#46; difficile</span> toxin gene expression are closely related to less chronic intestinal inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">37</span></a> Another trial in mice showed that side chains of pectin not only increased the levels of prebiotic effects but also downregulated inflammatory cytokines &#40;IL-6&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">38</span></a> The clinical trial with more patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>103&#41; demonstrated a lack of clinical benefit in using prebiotic supplementation in active Crohn&#39;s disease&#59; however&#44; this warrants further investigation in maintaining remission or other unexplored areas&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Synbiotic</span><p id="par0130" class="elsevierStylePara elsevierViewall">Probiotic therapy can be improved by adding a prebiotic&#59; allowing a better substrate for bacterial growth&#46; This combination is called synbiotic&#46; A pilot study showed that combining a probiotic like <span class="elsevierStyleItalic">Bifidobacterium longum</span> and a prebiotic like inulin promotes short-term active clinical UC improvement and decreases inflammatory cytokines&#44; such as TNF&#945; and IL1a&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">39</span></a> Another study showed histological improvement and TNF&#945; levels in biopsies at 3 months<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">40</span></a> and that preparations composed of six probiotic strains&#44; and a prebiotic of FOS resulted in decreased inflammatory markers in the synbiotic group&#46; In terms of clinical&#44; serologic&#44; and endoscopic activity levels a statistically significant improvement of synbiotic versus placebo was shown&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">41</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Newer data showed that a combination of Lactobacillus probiotics and prebiotics had a significant effect in remission only in patients with UC &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41; and combination with <span class="elsevierStyleItalic">Saccharomyces boulardii&#44; Lactobacillus&#44; and VSL&#35;3</span> probiotics in CD could be potentially worthy&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">33</span></a> However&#44; information regarding synbiotic studies has a low number of patients and this precludes making assumptions&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Antibiotics</span><p id="par0140" class="elsevierStylePara elsevierViewall">Dysbiosis is an important cause of pathogenesis in IBD and its alteration with the use of antibiotics is a potential therapy&#59; however&#44; based on several studies&#44; antibiotics play a role in the development of IBD by leading to dysbiosis and reducing bacterial diversity&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">42</span></a> There is an upward trend of data in favor of antibiotic use for IBD flare-ups&#44; and no association exists between the use of antibiotics and the development of IBD in early stages of life&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">43</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Regarding active UC&#44; data from meta-analyses suggest that antibiotic use maintain remission in 64&#37; compared to placebo&#44; 48&#37;&#44; favoring its use in UC&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">44</span></a> However&#44; the heterogeneity among studies showed that intravenous antibiotics in the long-term are not helpful in UC activity&#46; Some other studies demonstrate that either antibiotic monotherapy or combinations help to achieve better clinical and endoscopic outcomes at 6 and 12 months&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">45</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">In CD&#44; antibiotics are used in treating primary active disease in luminal disease&#44; fistulizing disease&#44; and septic complications such as abscesses or post-operative infections&#46; Information from meta-analyses and Cochrane data suggest that either luminal antibiotics or other type of antibiotics have a modest benefit against active CD and may not be clinically meaningful in the short-term or as maintenance of remission with a clinical endpoint at 52 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">46</span></a> Moreover&#44; the benefit of using antibiotics with immunomodulators or anti-TNF therapy in CD has little benefit in patients at high risk for recurrence&#44; with weak supporting evidence and a need for further evaluation&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">47</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The use of antibiotics in pouchitis&#44; acute or chronic&#44; has different managements depending on data&#46; A meta-analysis shows that antibiotics induce remission with a rate of 74&#37; in chronic pouchitis &#40;95&#37; CI&#58; 56&#8211;93&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Another meta-analysis that included prevention and treatment of pouchitis showed good effectiveness of ciprofloxacin in acute and chronic pouchitis&#59; however&#44; with a low effectiveness of metronidazole&#46; Furthermore&#44; current data in terms of pouchitis prevention is inconclusive&#44; powered studies are needed to determine its effectiveness&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">48</span></a> In chronic pouchitis&#44; antibiotic use promotes microbiome-associated resistant strains&#46; This suggests that new schemes of antibiotic therapy and short-term antibiotic alternation should be used&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">49</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Fecal microbiota transplantation &#40;FMT&#41;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Fecal microbiota transplantation is a process in which a fecal suspension from a healthy individual is transferred to a recipient&#46; This process was originally designed as part of the treatment of refractory <span class="elsevierStyleItalic">Clostridiodes difficile</span>&#59; however&#44; there is robust information about its use in IBD including 9 meta-analyses&#44; 4 RCT&#44; and many cohort studies &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">The information among meta-analyses is heterogeneous due to the information included and the outcomes reviewed&#46; Induction of remission of active UC with FMT was significantly more effective than placebo in the four published RCT with 28&#37; in the FMT group versus 9&#37; in placebo groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;64&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;&#46; The latest meta-analysis including 4 RCT and 23 cohort studies&#44; 21&#37; of patient achieved clinical remission &#40;CR&#41; with a high risk of heterogeneity&#46; FMT was associated with clinical improvement and endoscopic remission&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">50&#44;51</span></a> Moreover&#44; FMT is associated with a significant increase in the mucosal gut of immunoregulatory cells and anti-inflammatory metabolism &#40;increase of butanoate&#41; and a reduction of Th17 proinflammatory pathways&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">52</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The first meta-analysis regarding the success of CD in CR showed a pooled estimate of 60&#46;5&#37; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#37;&#41;&#59; however&#44; a more recent meta-analysis showed a pooled portion of CR of 30&#37; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>75&#37;&#41; with moderate heterogeneity and lower than previous data&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">50&#44;53</span></a> The main limitation among studies with CD and FMT is the poor correlation between clinical and endoscopic outcomes and the lack of data in this topic due the low prevalence of CD&#59; most information is from cohort studies and case reports&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">When IBD patients are divided into subgroups according to disease severity&#44; information shows that patients with moderate-severe disease from cohort studies could achieve more CR than those with mild-moderate disease&#59; however&#44; in RCT&#44; all patients included had mild-moderate disease severity&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">50</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">One of the most important characteristics of FMT is its safety&#46; Common adverse events related to patients treated with FMT included gastrointestinal system diarrhea &#40;13&#37;&#41;&#44; abdominal distention&#47;flatulence &#40;11&#46;6&#37;&#41;&#44; nausea&#47;vomiting &#40;6&#46;1&#37;&#41;&#44; abdominal pain &#40;5&#46;5&#37;&#41; and others&#46; Most of the complications like fever&#44; sore throat&#44; and gastrointestinal complaints were self-limiting lasting 24<span class="elsevierStyleHsp" style=""></span>h&#46; The reports of death and worse outcomes are scarce in the current information&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">51&#44;54</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">In terms of preparation of the sample for FMT according to current information&#44; the FMT donor is predominantly a man less than 30-years-old&#46; This could be explained by the higher prevalence of irritable bowel syndrome in women&#46; There is still controversy about the perfect stool donor&#59; in available data&#44; a close relative or friend was chosen&#46; A recent study indicates the importance of matching donors and patients for long-term maintenance of UC&#59; siblings&#8217; relationship has a significantly higher maintenance rate compared with a parent-child relationship&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">55</span></a> Information using mice models suggests a core transferable microbiota is necessary in responders to faecal microbiota transplant in UC to trigger an adequate immune reaction&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">56</span></a> No significant difference exists between using a frozen-stool FMT compared to fresh stool or the delivery route used &#40;either common upper GI or common lower GI&#41; in UC or CD&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">50</span></a> Furthermore&#44; from 338 clinical trials regarding FMT&#44; only 10 studies had the characteristics of FMT therapy in IBD patients&#46; In <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> are included the current studies from clinicals about FMT and IBD research&#46; However&#44; more data is needed in RCT and prospective studies to evaluate specific donors&#8217; microbiome characteristics&#44; the diet that FMT donors are eating due to its relevancy in the outcome of this treatment&#44; and specific therapies used in transplanted patients such as mesalazine or biologic because these data are important considerations for future research&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Areas under research&#58; synthetic mixtures of microbes</span><p id="par0190" class="elsevierStylePara elsevierViewall">Live biotherapeutic products &#40;LBPs&#41; are a mixture of protective commensal bacteria that modulate inflammation through several levels including interaction with inflammosome and tolerogenic responses&#46; SER-109&#44; a mixture of bacterial spores from 50 bacterial species from healthy donors&#8217; fecal matter shows promise to regulate immune responses and several other trials are underway&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">57</span></a> Furthermore&#44; the precise edition of microbiota composition can ameliorate adverse effects of dysbiosis&#46; Investigational microbe-based immunotherapy called QBECO&#44; formulated from inactivated strains of a gut pathogen showed objective reduction of UC disease pathology by activation of the immune system&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">58</span></a> Other experimental studies in mice showed that the addition of tungstate-mediated microbiota reduced severity of intestinal inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">59</span></a></p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusion</span><p id="par0195" class="elsevierStylePara elsevierViewall">The last decades show a trend toward an increase in IBD and the role of the microbiome in its development and pathogenesis&#46; Several hypotheses about dysbiosis and immuno-regulation correlate with the phenotype of IBD&#46; Many therapies beside the use of steroids&#44; immunomodulators or biologic therapy are still in a constant investigational process&#46; Hereby&#44; several options for the treatment of IBD to ameliorate dysbiosis were included&#59; some of them have been fully studied but others are under development&#46; The role of novel therapies&#44; such as FMT and precision medicine&#44; is growing and further evaluation of these therapies is needed&#46; There are some characteristics of the FMT donors that should be controlled more in future studies such as a donors&#8217; diet in order to assess all possible variables that limit FMT efficacy&#46; According to the knowledge in microbiome pathophysiology in IBD&#44; the study of the microbiome population should be included in all the future RCTs regarding this topic&#46; Limitations in Its current study includes the multifactorial pathophysiology of IBD&#44; a lack of evidence in certain modalities of treatment&#44; and some of the data used are based on experimental models and still need validation on clinical grounds&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0200" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interests</span><p id="par0205" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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              "identificador" => "abst0005"
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          "identificador" => "xpalclavsec1562076"
          "titulo" => "Keywords"
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          "identificador" => "xres1779217"
          "titulo" => "Resumen"
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          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Methods"
          "secciones" => array:12 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Search strategies"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Data collection and quality assessment of studies"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Normal immune regulation"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Microbiota in immune-regulation"
            ]
            4 => array:3 [
              "identificador" => "sec0035"
              "titulo" => "Pathogenesis in IBD"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Immune-regulation in IBD"
                ]
                1 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "Microbiota in IBD"
                ]
              ]
            ]
            5 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Treatment"
            ]
            6 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Probiotics"
            ]
            7 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Prebiotics"
            ]
            8 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Synbiotic"
            ]
            9 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Antibiotics"
            ]
            10 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Fecal microbiota transplantation &#40;FMT&#41;"
            ]
            11 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Areas under research&#58; synthetic mixtures of microbes"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conclusion"
        ]
        7 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Funding"
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        8 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conflicts of interests"
        ]
        9 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2021-06-21"
    "fechaAceptado" => "2021-08-29"
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Inflammatory bowel disease"
            1 => "Microbiome"
            2 => "Microbiota"
            3 => "Microbiota transplantation"
          ]
        ]
      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1562077"
          "palabras" => array:4 [
            0 => "Enfermedad inflamatoria intestinal"
            1 => "Microbioma"
            2 => "Microbiota"
            3 => "Trasplante microbiota"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The incidence of inflammatory bowel disease &#40;IBD&#41; is increasing&#46; Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations&#46; We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation&#44; and therapies that can modify microbiota&#46; A comprehensive systematic literature search was performed through April 2020 in PubMed&#44; Web of Science&#44; the Cochrane Library&#44; and clinicaltrials&#46;gov&#46; Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD&#46; This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation&#44; immune pathophysiology of IBD&#44; and shows the evidence of several therapeutic targets to change microbiome in patients with IBD&#44; such as prebiotics&#44; probiotics&#44; antibiotics&#44; fecal microbiota transplant&#44; and others&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La incidencia en enfermedad inflamatoria intestinal &#40;EII&#41; va en aumento&#46; El microbioma es uno de los factores m&#225;s importantes en su desarrollo y afecta los diferentes escenarios cl&#237;nicos en pacientes con EII dependiendo de su composici&#243;n y diferentes alteraciones&#46; Se realiz&#243; una revisi&#243;n sistem&#225;tica para discutir la asociaci&#243;n entre el microbioma y EII relacionado con inmunorregulaci&#243;n y las terapias que pueden modificar la microbiota&#46; Se realiz&#243; una b&#250;squeda en la literatura hasta abril de 2020 en Pubmed&#44; Web of Science&#44; Cochrane library y clinicaltrials&#46;gov&#46; La inclusi&#243;n del material requiere EII&#44; inmunorregulaci&#243;n y las terapias alternativas para EII&#46; Este estudio ayuda a explicar el origen multifactorial de la diversidad del microbioma incluyendo la inmunorregulaci&#243;n normal&#44; fisiopatolog&#237;a inmuno de EII y muestra la evidencia de diferentes blancos terap&#233;uticos para cambiar el microbioma en pacientes con EII como prebi&#243;ticos&#44; probi&#243;ticos&#44; antibi&#243;ticos&#44; trasplante de materia fecal&#44; entre otros&#46;</p></span>"
      ]
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">RCT&#44; randomized control trial&#59; UC&#44; ulcerative colitis&#59; CD&#44; Crohn&#39;s disease&#59; CR&#44; clinical remission&#59; NR&#44; not registered&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author&#47;year&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Studies&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study of donors&#8217; microbiome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study of donors&#8217; diet&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disease activity&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FMT route&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adverse effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Colman et al&#46;&#47;2014<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">53</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 cohort studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>8 case studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">122 patients79 UC&#59; 39 CD&#44; 4 IBD unclassified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#37; mild&#47;moderate13&#37; moderate&#8211;severe16&#37; severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refractory therapy 8&#37;Active disease 44&#37;Refractory pouchitis 4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Single NJ tube&#47;Colonoscoppy&#47;Daily enemas&#47;Gastroscopy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Overall CR 45&#37;UC CR 22&#37;&#40;95&#37; CI 10&#46;4&#8211;40&#46;8&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;CD CR60&#37; &#40;95&#37; CI 28&#46;4&#8211;85&#46;6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#8211;05&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; abdominal tenderness&#44; diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shi et al&#46;&#47;2016<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">60</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 cohort studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>8 case studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>2 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">234 UC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enema&#47;Colonoscopy&#47;Gastroscopy&#47;Nasogastric tube&#47;Nasoduodenal tube&#47;Endoscopic cecostomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Overall CR 41&#46;58&#37; &#40;95&#37; CI 24&#46;7&#8211;58&#46;7&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>36&#46;5&#37;&#41;65&#46;2&#37; Clinical response &#40;95&#37; CI 43&#46;7&#8211;83&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; diarrhea&#44; bloating&#44; worsening colitis&#44; urgent colectomy &#40;placebo&#41;&#44; rectal abscess&#44; perforation&#44; CMV&#44; cervix carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sun et al&#46;&#47;2016<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">61</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 cohort studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1 case&#8211;control <span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>2 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">133 UCAdults <span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Endoscopic scores&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enema&#47;NJ&#47;Colonoscopy&#47;Gastroscopy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UC CR 30&#46;4 &#40;95&#37;&#44; CI 22&#46;6&#8211;30&#46;4&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; diarrhea&#44; abdominal cramping&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Costello et al&#46;&#47;2017<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">62</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 cohort studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">168 UC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild&#8211;moderate majority of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasogastric&#47;NJ&#47;endoscopic duodenal&#44; enema&#44; colonoscopy or rectal tube&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UC CR 28&#37; &#40;95&#37; CI 1&#46;82&#8211;7&#46;39&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worsening colitis&#44; small intestine CD&#44; gastrointestinal complaints&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paramsothy et al&#46;&#47;2017<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">63</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 cohort studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>14 case studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">661 patients&#44;555 UC&#59; 83 CD&#59; 23 CD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#37; mild&#47;moderate12&#37; moderate&#47;severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;4&#37; active disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasogastric&#47;Gastroscopy&#47;Colonoscopy&#47;Enema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UC CR 33&#37; &#40;95&#37; CI 23&#8211;43&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>001&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>54&#37;&#41;&#44; CD CR 52&#37; &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40&#8211;64&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>001&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>58&#37;&#41;&#44; pouchitis CR 21&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bloating&#44; diarrhea&#44; flatulence&#44; abdominal pain&#44; borborygmus&#44; fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Narula et al&#46;&#47;2017<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">64</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">277 UC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; mild&#47;moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasoduodenal&#47;Colonoscopy&#47;Enema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UC CR 42&#46;1&#37; &#40;95&#37; CI 3&#8211;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No statistical difference in adverse effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cao et al&#46;&#47;2018<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">65</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 cohort studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">446 UC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RCT 100&#37;mild&#47;moderateCohortsNR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasogastric&#47;NJ&#47;endoscopic duodenal&#44; enema&#44; colonoscopy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UC CR 28&#46;9 &#40;<span class="elsevierStyleItalic">p</span>0&#46;59&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;Clinical response 46&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fang et al&#46;&#47;2018<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 cohort studies<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">459 patientsUC 365CD 94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RCT100&#37; mild&#47;moderateCohort studies28&#37; mild&#47;moderate12&#37; moderate&#47;severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;5&#37;Refractory7&#46;8&#37; Active disease6&#46;9&#37; Hormone dependent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasogastric&#47;NJ&#47;endoscopic duodenal&#44; enema&#44; colonoscopy or rectal tube&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Overall CR 28&#46;8&#37;UC CR 21&#37; &#40;95&#37; CI&#58; 8&#8211;37&#41;CD CR 30&#37; &#40;95&#37; CI&#58; 10&#8211;48&#41;Clinical response 53&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrhea&#44; abdominal pain&#44; borborygmus&#44; fever&#44; urtircaria&#44; kidney stones&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Imdad et al&#46;&#47;2018<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">51</span></a> Cochrane Library&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">277 UC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RCT100&#37; mild&#47;moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasoduodenal&#47;Colonoscopy&#47;Enema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 weeks CR 37&#37; &#40;95&#37; CI&#58; 1&#46;07&#8211;3&#46;86&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#37;&#41;Clinical response 49&#37; &#40;95&#37; CI 0&#46;98&#8211;2&#46;95&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No serious adverse events between groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">FMT for IBD reviews and meta-analysis&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">IBD&#44; inflammatory bowel disease&#59; UC&#44; ulcerative colitis&#59; CD&#44; Crohn&#39;s disease&#59; CDI&#44; <span class="elsevierStyleItalic">Clostridium difficile</span> infection&#59; FMT&#44; fecal microbiota transplant &#42;&#42;Information extracted from clinicaltrials&#46;gov&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Title&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Conditions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Interventions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fecal Microbiota Transplantation in Pediatric Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IBDCDUC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase 1&#58;FMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5025 CD25 UC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Failing primary therapy or in a flare&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Standardized Fecal Microbiota Transplantation for Inflammatory Bowel Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unknown status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results Available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IBDCDUC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase 2&#58;FMTDrug&#58; Mesalazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4020 CD20 UC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Efficiency&#44; durability and safety of standardized FMT for IBD treatment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Efficacy of Fecal Microbiota Transplantation for Inflammatory Bowel Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recruiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UCCDConstipation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase 3&#58;FMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Efficiency and safety of FMT in a series of 80 patients with moderate to severe UC and CD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fecal Microbiota Transplantation for Health Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enrolling by invitation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UCIBSCD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase&#58; NAFMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Select donors of fecal samples for carrying out the procedure of fecal transplantation of microbiota&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FMT in inflammatory bowel disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recruiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FMTCDUCMicroscopic colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CohortFMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluating the use of faecal microbiota transplantation amongst patients with Inflammatory Bowel Disease and Microscopic Colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICON-2 FMT and Bezlotoxumab Compared to FMT and Placebo for Patients With IBD and CDI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recruiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IBDCDI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase2&#58;Drug&#58; BezlotoxumabDrug&#58; PlaceboDrug&#58; FMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical and microbiological impacts of FMT in combination with Bezlotoxumab &#40;bezlo&#41; compared to FMT in combination with placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fecal Transplantation for Inflammatory Bowel Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Terminated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IBD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase 1&#58;FMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FMT improvement for colitis in IBD patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Manipulating the microbiome in IBD by antibiotics and FMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Active&#44; not recruiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UC exacerbation&#44; severe activityCrohn&#39;s colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase 4&#58;Drug&#58; antibioticsDrug&#58; corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assess the outcome of FMT in those not responding to five days of therapy with antibiotics or corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fecal Microbiota Transplant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Active&#44; not recruiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No results available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CDIIBDCDUC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase&#58; NAFMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Determine the effect of FMT on the gut microbiota through the use of 454 pyrosequencing before and after transplantation in these patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bacteriotherapy in pediatric inflammatory bowel disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Has results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IBDCDUC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase 1&#58;FMT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Learn whether this experimental therapy delays the need for starting additional medications to treat pediatric IBD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Current ongoing clinical trials for FMT in IBD&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:65 [
            0 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changing global epidemiology of inflammatory bowel diseases&#8212;sustaining healthcare delivery into the 21st century"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;N&#46; Ananthakrishnan"
                            1 => "G&#46; Gilaad"
                            2 => "S&#46;C&#46;N&#46; Kaplan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Progression of inflammatory bowel diseases throughout latin America and the Caribbean&#58; a systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "P&#46;G&#46; Kotze"
                            1 => "F&#46;E&#46; Underwood"
                            2 => "A&#46; Omar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2019.06.030"
                      "Revista" => array:4 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol"
                        "fecha" => "2019"
                        "paginaInicial" => "1"
                        "paginaFinal" => "9"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence and prevalence of in fl ammatory bowel disease in Mexico from a nationwide cohort study in a period of 15 years &#40;2000&#8211;2017&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Sarmiento-aguilar"
                            1 => "F&#46;J&#46; Bosques-padilla"
                            2 => "Y&#46; Cortes-aguilar"
                            3 => "R&#46;M&#46; Miranda-cordero"
                            4 => "J&#46;S&#46; Jacobo-karam"
                            5 => "E&#46;F&#46; Bermudez-villegas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Medicine &#40;Baltimore&#41;"
                        "fecha" => "2019"
                      ]
                    ]
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                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Environmental triggers in IBD&#58; a review of progress and evidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46;N&#46; Ananthakrishnan"
                            1 => "C&#46;N&#46; Bernstein"
                            2 => "D&#46; Iliopoulos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrgastro.2017.136"
                      "Revista" => array:2 [
                        "tituloSerie" => "Nat Publ Gr"
                        "fecha" => "2017"
                      ]
                    ]
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              "identificador" => "bib0350"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "From genetics to epigenetics roles of epigenetics in inflammatory bowel disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Z&#46; Zeng"
                            1 => "A&#46; Mukherjee"
                            2 => "H&#46; Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fgene.2019.01017"
                      "Revista" => array:6 [
                        "tituloSerie" => "Front Genet"
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Article information

ISSN: 02105705
Original language: English

DOI:10.1016/j.gastrohep.2021.08.008

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Year/Month	Html	Pdf	Total

2024 October	28	11	39
2024 September	21	3	24
2024 August	14	0	14
2024 July	23	0	23
2024 June	29	7	36
2024 May	31	8	39
2024 April	35	9	44
2024 March	38	9	47
2024 February	16	3	19
2024 January	6	0	6
2023 December	10	0	10
2023 November	11	0	11
2023 October	23	0	23
2023 September	10	0	10
2023 August	23	0	23
2023 July	14	0	14
2023 June	26	3	29
2023 May	34	0	34
2023 April	29	1	30
2023 March	8	9	17
2023 February	4	6	10
2023 January	9	7	16
2022 December	58	8	66
2022 November	10	11	21
2022 October	20	20	40
2022 March	0	1	1
2022 January	0	1	1
2021 December	0	2	2
2021 November	0	1	1
2021 October	0	3	3

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