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As Doenças Inflamatórias Intestinais (DII), como a colite ulcerativa e a doença de Crohn, são resultados de uma resposta imune desregulada no intestino de indivíduos geneticamente suscetíveis apresentando disbiose intestinal. Essas doenças geralmente são tratadas com anticorpos monoclonais, como o anti-TNF, Infliximab (IFX). No entanto, pouco se sabe como o bloqueio do TNF afeta a resposta do hospedeiro quando ocorre uma nova quebra da homeostase intestinal, durante a recidiva da doença. Neste estudo, avaliamos os efeitos tardios do tratamento com IFX na colite experimental com um novo desafio de disbiose. Camundongos tratados com IFX tiveram remissão da colite. No entanto, o tratamento não protegeu contra a recidiva da doença, o que resultou no aumento de células mononucleares circulantes e diminuição de neutrófilos, em contraste com a redução da atividade de macrófagos e aumento da infiltrado de neutrófilos no cólon após o desafio. Esses animais também apresentaram diminuição da barreira linfocitária epitelial e aumento de linfócitos na lâmina própria do cólon, que também continha elevado número de células dendríticas inflamatórias CD11b+CD11c+CD103-. O tratamento da colite com IFX seguido de um desafio de microbiota levou à redução de linfócitos TCD4, TCD8 e ?? intraepiteliais, com acúmulo de células T ativadas, memória residentes e efetoras na lâmina própria, em comparação com o número reduzido desses linfócitos na ausência de tratamento com IFX. Além disso, o bloqueio do TNF reduziu a expressão de IL-1? e IL-6 e aumentou a expressão de CYP11B1, uma enzima esteroidogênica responsável pela produção de cortisol anti-inflamatório. Porém o desafio antigênico elevou significativamente a expressão de IL-13, mas reduziu a expressão das enzimas esteroidogênicas, CYP11A1 e CYP11B1O. O mais interessante é que a permeabilidade intestinal foi aumentada, assim como a atividade de proliferação das células nos linfonodos mesentéricos. Esses dados sugerem que, embora o IFX possa controlar a inflamação na colite aguda, seus efeitos tardios comprometem a capacidade do hospedeiro de lidar com um novo desafio, como uma disbiose intestinal que ocorre durante a recaída da doença / Inflammatory Bowel Diseases (IBD), such as ulcerative colitis and Crohn\'s disease, are the result of a dysregulated immune response in the intestine of genetically susceptible individuals presenting with intestinal dysbiosis. These diseases are usually treated with monoclonal antibodies, such as anti-TNF, Infliximab (IFX). However, little is known about how TNF blockade affects host response when a new break in intestinal homeostasis occurs during relapse of the disease. In this study, we evaluated the late effects of IFX treatment in experimental colitis with a new challenge of dysbiosis. Mice treated with IFX had remission of colitis. However, the treatment did not protect against disease recurrence, which resulted in increased circulating mononuclear cells and decreased neutrophils, in contrast to reduced macrophage activity and increased neutrophil infiltrate in the colon after challenge. These animals also had a decrease in the lymphocyte epithelial barrier and increased lymphocytes in the lamina propria of the colon, which also contained a high number of inflammatory dendritic cells CD11b+CD11c+CD103-. Treatment of IFX colitis followed by a microbiota challenge led to reduction of intraepithelial TCD4, TCD8 and ?? lymphocytes with accumulation of activated T cells, resident and effector memory in the lamina propria, compared to the reduced number of these lymphocytes in the absence of treatment with IFX. In addition, TNF blockade reduced IL-1? and IL-6 expression and increased expression of CYP11B1, a steroidogenic enzyme responsible for the production of anti-inflammatory cortisol. However, antigen challenge significantly elevated IL-13 expression, but reduced expression of steroidogenic enzymes, CYP11A1 and CYP11B1. Interestingly, the intestinal permeability was increased, as was the proliferation activity of the cells in the mesenteric lymph nodes. These data suggest that although IFX can control inflammation in acute colitis, its late effects compromise the host\'s ability to cope with a new challenge, such as intestinal dysbiosis that occurs during relapse of the disease

L’étiologie exacte des maladies inflammatoires chroniques de l’intestin (MICI) reste actuellement méconnue. Mais un déséquilibre de la flore bactérienne, plus connu sous le nom de dysbiose et se traduisant par une augmentation de bactéries potentiellement pathogènes versus une diminution de bactéries bénéfiques, est démontré en permanence. De précédentes études ont permis de mettre en évidence la présence de souches pathogènes d’E. coli chez les patients atteints de la maladie de Crohn (MC). Ces souches appartiennent au pathovar Adherent Invasive E. coli (AIEC) et sont caractérisées par leur capacité à adhérer et à envahir les cellules épithéliales intestinales, à survivre et à se multiplier dans les macrophages en induisant une synthèse intense de TNF. La mise en évidence de ce pathovar a essentiellement été réalisée sur des biopsies de patients présentant une MC. Et bien que les mécanismes de pathogénicité et de virulence de la souche AIEC soient clairement déterminés, il n’existe pas d’études approfondies sur la prévalence des AIEC au niveau des matières fécales chez les patients atteints de MICI en comparaison à des individus sains. Ainsi, ce projet de thèse s’inscrit dans une meilleure compréhension de l’implication de ce pathovar AIEC dans les MICI au niveau luminal. Cette thèse cible différents points: prévalence et détection des AIEC, leur proportion relative par rapport à la flore E. coli totale, leur capacité d'invasion, leur phylogroupe ainsi que leur transmissibilité. A l’issue de ce travail, nous montrons que les AIEC sont retrouvés au niveau luminal chez les patients atteints de la MC mais également chez les patients présentant une rectocolite hémorragique, avec une détection des AIEC chez 33% et 2% respectivement. En outre, ces études ont permis de montrer une prévalence plus forte de ce pathovar dans les matières fécales d’individus sains (51%) en comparaison aux patients atteints de MICI. Et lorsque les AIEC sont présents, que ce soit chez les patients atteints de MICI et chez les témoins, ils représentent en moyenne 20 à 30% de la flore E. coli. Nous avons également pu montrer qu’il n’existe pas de différences significatives des scores d’invasion des isolats AIEC chez les patients atteints de MICI et chez les sujets sains. Certaines souches d’AIEC, isolées chez les patients atteints de MC et chez les sujets sains, ont été caractérisées génétiquement par la technique d’électrophorèse sur gel en champ pulsé. Sur ces souches, différents profils génétiques ont été obtenus attestant de la forte variabilité intra- et interindivuelle des AIEC. En conclusion, les AIEC, au vue de leur forte prévalence chez des sujets en bonne santé, seraient plutôt à reconsidérer comme des pathobionts ce qui définit un symbionte pouvant acquérir des propriétés virulentes chez un hôte prédisposé génétiquement en raison de facteurs environnementaux et/ou diététiques et ainsi favoriser l’inflammation intestinale. / Many studies have reported an imbalance of bacterial flora in patients with inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), defined as a dysbiosis, and resulting in an increase in potentially pathogenic bacteria versus a decrease in beneficial bacteria. Previous studies have highlighted the presence of pathogenic strains of E. coli in patients with CD. These strains belong to the pathovar Adherent Invasive E. coli (AIEC) and are characterized by their ability to adhere and invade intestinal epithelial cells, to survive and to multiply in macrophages by inducing an intense synthesis of TNF. In recent years, many studies established a link between AIEC pathovar and CD. Many of these studies have been performed on biopsies of patients with CD. And although the mechanisms of pathogenicity and virulence of the AIEC strain are clearly determined, there are no in-depth studies on the prevalence of AIEC in feces in IBD patients in comparison to healthy individuals. Thus, the goal of this thesis project is to better understand the involvement of AIEC pathovars in IBD at the luminal level. This thesis is based more precisely on the study of the prevalence of AIEC in feces of patients with IBD in comparison to healthy subjects, targeting different points: prevalence and detection of AIEC, their relative proportion compared to total E. coli flora, their invasion capacity, their phylogroup as well as their transmissibility. AIEC are found at luminal level in patients with CD but also in patients with UC, with detection of AIEC in 33% and 2% respectively. In addition, a higher prevalence of these pathovar is present in the feces of healthy individuals (51%) compared to patients with IBD. And when AIEC are present, both in IBD patients and in controls, they represent on average 20 to 30% of the E. coli flora. We have also been able to show that there are no significant differences in AIEC invasion scores in patients with IBD and in healthy subjects. Some AIEC strains, isolated in patients with CD and in healthy subjects, have been genetically characterized by pulsed-field gel electrophoresis. Different genetic profiles have been obtained attesting the high intra- and interindividual variability of AIEC strains. In conclusion, because of their high prevalence in healthy individuals, AIEC should be reconsidered as pathobionts, which defines a symbiont acquiring virulent properties in a genetically predisposed host due to environmental and / or dietary factors and thus promoting intestinal inflammation.

As we age, the risk for gut issues, such as smooth muscle tone, may be an underlying indirect or direct cause or risk factor for many age-related issues, such as frailty. Consequences of decreased motility and depleted epithelial barrier may result in nutrient deficiencies that may increase the risk for malnutrition (Brownie, 2006). Further, there is increasing evidence that there is a gut-brain-axis relationship that may influence cognition and mental health issues, such as depression and anxiety. While there are relationships established, the interconnections of these factors have yet to be fully understood. This dissertation examined several relationships specific to nutrient intake, physical function, and depression in older adults while probing for a moderating effect of gut health. Looking further at this theory of the gut-brain bi-directional relationship, an additional gut health assessment was further examined to investigate the relationship with cognitive performance. Participants were from two separate but complementary data sets. The first data set from the National Health and Nutritional Examination study included a depression outcome analytic sample and a physical function analytic sample who had valid data on nutrient intake, bowel measures, demographic characteristics, depression scores, physical function measurements, and total BMI. The depression analytic sample had a total of 1918 participants with a mean age of 73.76 years, and 1864 participants with a mean age of 73.28 years in the physical function analytic sample. The available nutrients within the data set were further broken down into several different components by a component factor analysis and each component used as a predictor. Two separate bowel measures were examined with one as a fecal incontinence measure and the other, the Bristol Stool Form Scale, as categorical (normal, constipation, or diarrhea). The second data set, the Nutraceutical Blueberry Study, had a total of 108 participants with a mean age of 73.42 years who had valid data on cognitive measures and a complete gut assessment. Among the depression analytic sample, there were significant moderating effects of fecal incontinence between several nutrient components and depression after accounting for the control variables. An additional moderated multivariate regression with only the significant components was carried out and resulted in only Component 9 (carbohydrates, sugar, beta-cryptoxanthin, and vitamin C) and Component 12 (alcohol) having the fecal incontinence measure as a significant moderator with depression as the outcome. Within the physical function analytical sample, the Bristol Stool Form Scale categorical measure was a significant moderator among Component 6 (MFA22_1, PFA18_4, PFA20_5, PFA22_5, and PFA 22_6) and physical function. Both the constipation and diarrhea categories were related to worse physical function, while in all groups, increase in nutrients from Component 6 resulted in better physical function. Within the second data set, AVLT and AVLT Delay had a significant quadratic relationship with bowel function. Within the four different groups in the bowel measure (gastric function, gastrointestinal inflammation, small intestine and pancreas, and colon), gastrointestinal inflammation with a negative association and the colon category with a positive association were significant. Among the AVLT Delay, gastrointestinal inflammation was also negatively associated significant predictor. Outcomes from the current study suggest that fecal incontinence was indicative as a moderator among the first data set, as well as significant predictor for AVLT and AVLT Delayed in relation to cognition in older adults. Although there were many relationships not found with bowel function as a moderator, the current findings suggest that more thorough measures in additional to microbiota measures could further provide possible directions for new therapeutics in psychological and cognitive therapy, as well as improving physical function in older adults.

Ces dernières années, l'implication du microbiote intestinal dans la physiopathogénie des maladies inflammatoires chroniques de l'intestin (MICI) a été mise en évidence. Le but de nos travaux est de déterminer l'impact de la dysbiose sur l'écosystème intestinal au cours des MICI. Ces trois études nous ont permis de confirmer le rôle central de la dysbiose associée aux MICI : d'une part comme outil potentiellement prédictif de rechute, précédant une inflammation locale ou systémique, d'autre part comme acteur dans l'apparition d'un déséquilibre de l'écosystème intestinal. Ce déséquilibre est marqué par l'altération de l'activité enzymatique du microbiote modifiant le pool d'acides biliaires dans la lumière intestinale et pouvant affecter les effets anti-inflammatoires de certains acides biliaires sur les cellules épithéliales intestinales participant ainsi à une inflammation chronique au cours des MICI. Par ailleurs, cette dysbiose est possiblement entretenue par un déficit en défensine hBD1 et HD5, perpétuant une inflammation chronique intestinale.Ces résultats renforcent le rôle proéminent du microbiote dans l'évolution des MICI et suggèrent que la restauration de la normobiose au cours de la maladie devrait être un nouveau but dans la prise en charge de ces patients. / In recent years, the involvement of intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) has been established. The aim of our study was to determine the impact of dysbiosis in intestinal ecosystem of IBD patients.These three studies allowed us to confirm the fundamental role of IBD-associated dysbiosis. First, IBD-associated dysbiosis has been identified as a potential predictive tool of relapse, before local or systemic inflammation. Second, IBD-associated dysbiosis has been involved as an actor in the emergence of an imbalance of intestinal ecosystem. This imbalance was characterised by an alteration of microbiota enzymatic activity leading to modifications in the luminal bile acid pool composition and may affect the anti-inflammatory effects of some bile acids on gut epithelial cells and could participate in the chronic inflammation loop of IBD. Moreover, a deficiency in the antimicrobial defense systems of defensins may be an explanation for the break of the antibacterial barrier function in inflammatory bowel diseases maintaining dysbiosis.These results reinforce the prominent role of the microbiota in the development of IBD and suggest that restoring normobiosis could be a new goal for optimal IBD management.

The intestinal tract of virtually any metazoan, including mammals, is colonized with a complex microbial community to which we refer as intestinal or gut microbiota. One of the roles of the healthy intestinal microbiota is to protect the host against gut colonization with pathogenic bacteria through a phenomenon known as colonization resistance (CR). Dysbiosis of the intestinal microbiota, usually as a result of an antibiotic treatment, may lead to the disruption of the CR, and subsequent colonization with bacterial pathogens. However, and despite the importance, the role of the microbiota dysbiosis on the gut colonization by many bacterial pathogens, such as multidrug resistant Enterobacteriaceae, has not been elucidated: the members of the microbiota that confer CR and factors that promote colonization remain mostly unknown. The general aim of this thesis has been to improve the understanding of the role of the microbiota dysbiosis in gut colonization by bacterial pathogens. For this purpose, 3 projects have been established. In the first project we tried to elucidate the role of the microbiota dysbiosis on colonization by multidrug resistant Enterobacteriaceae (MRE) in mice. In the second project we investigated the risk factors and members of the microbiota associated with the MRE colonization in hospitalized patients. MRE infections represent a great threat for hospitalized patients. Specifically, acute leukemia patients are often colonized with MRE, probably due to the impaired CR as a result of intensive antibiotic treatments these patients receive. In the third project we studied the role of the microbiota dysbiosis on the development of Epizootic Rabbit Enteropathy (ERE). ERE is a severe gastrointestinal disease with a high percentage of mortality that occurs in young rabbits during first weeks post-weaning. ERE rabbits have been shown to suffer microbiota dysbiosis during the development of the disease. Moreover, the disease could be reproduced by contact between healthy and sick animals and by administration of cecal contents from ERE rabbits to healthy rabbits, suggesting that a pathogenic agent may be involved in the development of this intestinal pathology, although no causative agent has been identified until now. / El tracto intestinal de prácticamente cualquier metazoo, incluidos los mamíferos, está colonizado por una compleja comunidad microbiana a la que nos referimos como microbiota intestinal. Uno de los papeles de la microbiota intestinal es proteger al huésped contra la colonización intestinal con bacterias patógenas a través de un fenómeno conocido como resistencia a la colonización (RC). La disbiosis de la microbiota intestinal, a menudo como resultado de un tratamiento antibiótico, puede conducir a la alteración de la RC y posterior colonización por patógenos bacterianos. Sin embargo, y pese a su importancia, el papel de la disbiosis de la microbiota en la colonización intestinal por muchos patógenos bacterianos, como son las Enterobacterias multirresistentes, no se ha esclarecido: los miembros de la microbiota que confieren RC y los factores que promueven la colonización siguen siendo desconocidos. El objetivo general de esta tesis ha sido mejorar la comprensión del papel de disbiosis de la microbiota en la colonización intestinal por patógenos bacterianos. Para ello se han establecido tres proyectos. En el primer proyecto investigamos el papel de disbiosis de la microbiota intestinal en la colonización por Enterobacterias multiresistentes (MRE) en ratones. En el segundo proyecto investigamos los factores de riesgo y los miembros de la microbiota asociados con la colonización por MRE en pacientes hospitalizados. Las infecciones por MRE representan una gran amenaza para los pacientes hospitalizados. Específicamente, MRE a menudo colonizan los pacientes con leucemia aguda, probablemente debido a que la RC está alterada como resultado de tratamientos antibióticos intensivos recibidos por estos pacientes. En el tercer proyecto investigamos el papel de la disbiosis microbiana en desarollo de Enteropatía Epizoótica de Conejo (ERE). ERE es una enfermedad gastrointestinal severa con un alto porcentaje de mortalidad que ocurre en conejos jóvenes durante las primeras semanas después del destete. Se ha demostrado que los conejos con ERE sufren disbiosis microbiana después del inicio de la enfermedad, aunque no está claro el papel de la disbiosis en el desarollo de la enfermedad. Además, la enfermedad puede ser reproducida por contacto entre animales sanos y enfermos y por la administración del contenido cecal de conejos con ERE a conejos sanos, lo que sugiere que un agente patógeno podría estar implicado en el desarrollo de esta patología intestinal, aunque hasta ahora no se ha logrado identificar ningún agente causal. / El tracte intestinal de pràcticament qualsevol metazoo, inclosos els mamífers, està colonitzat per una complexa comunitat microbiana a la qual ens referim com microbiota intestinal. Un dels papers de la microbiota intestinal és protegir a l'hoste contra la colonització intestinal amb bacteris patògens a través d'un fenomen conegut com a resistència a la colonització (RC). La disbiosis de la microbiota intestinal, frecuentment com a resultat d'un tractament antibiòtic, pot conduir a l'alteració de la RC i posterior colonització per patògens bacterians. No obstant això, i malgrat la seva importància, el paper de la disbiosis de la microbiota en la colonització intestinal per molts patògens bacterians, com són les Enterobacteries multirresistentes, no s'ha esclarit: els membres de la microbiota que confereixen RC i els factors que promouen la colonització segueixen sent desconeguts. L'objectiu general d'aquesta tesi ha estat millorar la comprensió del paper de la disbiosis de la microbiota en la colonització intestinal per patògens bacterians. Per a això s'han establert tres projectes. En el primer projecte vam investigar el paper de la disbiosis de la microbiota intestinal en la colonització per Enterobacteries multiresistentes (MRE) en ratolins. En el segon projecte, investiguem els factors de risc i els membres de la microbiota associats amb la colonització per MRE en pacients hospitalitzats. Les infeccions per MRE representen una gran amenaça per als pacients hospitalitzats. Específicament, MRE sovint colonitza els pacients amb leucèmia aguda, probablement a causa de que la RC està alterada com a resultat de tractaments antibiòtics intensius rebuts per aquests pacients. En el tercer projecte, vam investigar el paper de la disbiosis microbiana en desenvolupament de l'Enteropatía Epizoótica de Conill (ERE). ERE és una malaltia gastrointestinal severa amb un alt percentatge de mortalitat que ocorre en conills joves durant les primeres setmanes després del deslleti. S'ha demostrat que els conills amb ERE sofreixen disbiosis microbiana després de l'inici de la malaltia, encara que no és clar el paper de la disbiosis en el desenvolupament de la malaltia. A més, la malaltia pot ser reproduïda per contacte entre animals sans i malalts i per l'administració del contingut cecal de conills amb ERE a conills sans, la qual cosa suggereix que un agent patogen podria estar implicat en el desenvolupament d'aquesta patologia intestinal, encara que fins ara no s'ha aconseguit identificar cap agent causal. / Djukovic, A. (2017). Role of intestinal dysbiosis on gut colonization by bacterial pathogens [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/90415 / TESIS

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As one of the most common medications, it is reasonable to assume that the adverse effects from nonsteroidal anti-inflammatory drugs (NSAIDs) are well understood. While this is the case for NSAID-induced gastropathy, NSAID-induced enteropathy is often clinically overlooked and has a pathogenesis that is incompletely understood. The goal of this study was to determine how alterations in the microbiota impact NSAID-induced intestinal injury. Initial studies explore how gastric acid secretion suppression substantially decreases Bifidobacteria in the small intestine, and emphasize how replenishment of these bacteria results in an amelioration of NSAID-induced enteropathy. Follow-up studies involved pretreating rats with specific bacteria that have conferred protection in other models of small intestinal injury. We examined the role that acetate may play in reducing the damage by evaluating bacteria that had an acetate production gene knocked out via homologous recombination. Protection levels were similar between wildtype and knockout bacteria, and it did not appear that acetate had a key role in damage reduction. Moreover, we found that changes in intestinal damage were dependent not only on the strain of bacteria used but also on the NSAID administered. None of the bacterial pretreatments tested protected against indomethacin- or diclofenac-induced small intestinal injury, and pretreatment with one specific bacterial strain resulted in a significant worsening of damage. To gain further insight as to the potential role of the microbiota in exacerbation of injury, we conducted studies using single antibiotics and antibiotic cocktails. No single antibiotic treatment conferred protection against naproxen-induced small intestinal injury, but an antibiotic cocktail decreased damage scores by ~46%. Furthermore we explored the effects of L-lactic acid supplementation of drinking water but this was unable to reduce naproxen-induced intestinal damage. Collectively, the work presented in this thesis provides novel insights on the relationship between alterations in the microbiota and susceptibility to NSAID-induced enteropathy. / Dissertation / Doctor of Philosophy (Medical Science)

Background: It has been hypothesized that dysbiosis plays a significant role in the pathogenesis of intestinal failure–associated liver disease (IFALD). Therefore, we aimed to investigate the effect of probiotics on IFALD in patients receiving parenteral support, namely home parenteral nutrition (HPN) and home intravenous fluids (HIVFs). Methods: We retrospectively reviewed charts of patients with intestinal failure who received HPN or HIVF for >2 weeks at our tertiary center between January 2005 and August 2016. We excluded patients <18 years of age, patients with other causes of liver disease, patients who used probiotics for <30 days, patients with <6 months' follow-up, and those who had long-term antibiotic use (>30 days). Bivariable and multivariable logistic regression analyses were used in this study. Results: A total of 282 patients who received parenteral support were included. Eighty-five percent of our sample received PN. A total of 78 (27.7%) patients used probiotics. The prevalence of IFALD in patients who used probiotics was 35.9% vs 54.4% in patients who did not use probiotics, P =.005. In multivariable analysis, only small-bowel length of 10-90 cm and HPN use showed a significant impact on IFALD, odds ratio (OR) = 4.394 (95% confidence interval [CI], 1.635-11.814; P =.003) and OR = 4.502 (95% CI 1.412-14.351; P =.011), respectively. Conclusion: Our study revealed that the prevalence of IFALD was comparable among the probiotic users and nonusers. Only small bowel length of 1090 cm and HPN use showed a significant impact on IFALD.

In severe cases of ulcerative colitis (UC) unresponsive to current treatment options, patients require a complete proctocolectomy, or surgical removal of the colon. Ileal pouch anal anastomosis (IPAA) has become the preferred surgical technique for patients who require surgery, as this method restores rectal function. This procedure is also used to treat colorectal cancers such as adenocarcinoma and familial adenomatous polyposis (FAP). The surgery involves an abdominal colectomy with the construction of an ileal pouch created from folded tissue recovered from the ileal portion of the small intestine. Up to 50% of patients who require IPAA surgery experience an episode of pouchitis, a non-specific inflammation of the constructed ileal pouch with unknown etiology. Several hypotheses have been proposed regarding the pathogenesis of pouchitis. Current theories include bacterial overgrowth due to fecal stasis, microbial imbalance (dysbiosis), immune alteration, genetic susceptibility, metaplasia, ischemic complications of surgery, a recurrence of UC, or even a novel form of inflammatory bowel disease. The efficacy of antibiotics and probiotics in treating pouchitis and maintaining remission underscores the importance of gut microbiota in the development of this condition. In the study, we aimed to characterize the intestinal bacterial communities that inhabit IPAA pouches of both UC and FAP patients, in an effort to investigate the hypothesis that bacterial dysbiosis is involved in the pathogenesis of pouchitis. Mucosal biopsy and stool samples were analyzed from patients with UC and pouchitis (UCP), healthy UC controls (HUC) and healthy pouches with a background of FAP (FAP). Samples were examined through analysis of terminal restriction fragment length polymorphisms (TRF) and DNA sequencing. The data presented here demonstrate that a microbial imbalance exists in pouchitis, as bacterial communities in pouchitis differ significantly from healthy UC pouches and pouches constructed for FAP. Both methods identified potential groups of organisms that may play a role in the development of pouchitis, including decreases in protective Lactobacillus and Bacteroides and increases in mucin-degrading Clostridium and Akkermansia. A better understanding of the factors driving the pathogenesis of pouchitis will not only benefit patients with this disease, but also lead to a better understanding of the complex relationship that exists between the human host and the diverse community of organisms that inhabit the gastrointestinal tract.