Microbiome Analysis of Mucosal Ileoanal Pouch in Ulcerative Colitis Patients Revealed Impairment of the Pouches Immunometabolites.

The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA. METHODS: For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2. RESULTS: IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids. CONCLUSIONS: Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation.

Review article: the impact of diet on ileoanal pouch function and on the pathogenesis of pouchitis.

BACKGROUND: There is expanding interest in the role that diet plays in ileoanal pouch function and in the pathogenesis of pouchitis. AIMS: To present a narrative review of published literature regarding the relationship of diet with pouch function and the pathogenesis of pouchitis, and to provide potentially beneficial dietary strategies. METHODS: Current relevant literature was summarised and critically examined. RESULTS: Dietary components influence pouch function via their effect on upper gastrointestinal transit, small bowel water content and the structure and fermentative activity of the pouch microbiota. FODMAPs in fruits and vegetables appear to affect pouch function the most, with intake positively associated with increased stool frequency and reduced consistency. Dietary factors that influence the pathogenesis of pouchitis appear different and, at times, opposite to those better for optimising function. For example, risk of pouchitis appears to be inversely associated with intake of fruits. The food components mechanistically responsible for this observation are not known, but a rich supply of fermentable fibres and micronutrients in such foods might play a beneficial role via modulation of microbial community structure (such as increasing diversity and/or changing microbial communities to favour 'protective' over 'pathogenic' bacteria) and function and/or anti-inflammatory effects. CONCLUSION: Available data are weak but suggest tailoring dietary recommendations according to pouch phenotype/behaviour and pouchitis risk might improve outcomes. More sophisticated dietary strategies that utilise the physiological and pathophysiological effects of dietary components on ileoanal pouches have potential to further improve outcomes. Well designed, adequately powered studies are required.

Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation.

Secondary bile acids (SBAs) are derived from primary bile acids (PBAs) in a process reliant on biosynthetic capabilities possessed by few microbes. To evaluate the role of BAs in intestinal inflammation, we performed metabolomic, microbiome, metagenomic, and transcriptomic profiling of stool from ileal pouches (surgically created resevoirs) in colectomy-treated patients with ulcerative colitis (UC) versus controls (familial adenomatous polyposis [FAP]). We show that relative to FAP, UC pouches have reduced levels of lithocholic acid and deoxycholic acid (normally the most abundant gut SBAs), genes required to convert PBAs to SBAs, and Ruminococcaceae (one of few taxa known to include SBA-producing bacteria). In three murine colitis models, SBA supplementation reduces intestinal inflammation. This anti-inflammatory effect is in part dependent on the TGR5 bile acid receptor. These data suggest that dysbiosis induces SBA deficiency in inflammatory-prone UC patients, which promotes a pro-inflammatory state within the intestine that may be treated by SBA restoration.

Obesity Is Associated with Decreased Risk of Clostridium difficile Infection in Hospitalized Patients with Pouchitis.

BACKGROUND: Clostridium difficile infection (CDI) is one of the leading causes of health-care-associated infections in the USA. There are limited data available regarding CDI in hospitalized patients with inflammatory bowel disease-related ileal pouch. AIMS: This study aimed to evaluate the demographics, clinical features, risk factors, and admission outcomes among hospitalized patients with CDI-related pouchitis (CDP). METHODS: Retrospective chart review was performed for patients who were admitted to our institute for pouchitis between 2013 and 2016 to identify patients with CDP. Logistic regression analysis was performed to assess the risk factors associated with CDP. RESULTS: A total of 160 subjects with pouchitis had a total of 218 admissions during the study period. Primary admission diagnosis was pouchitis or inflammatory bowel disease flare-up for 202 (93%) admissions. Clostridium difficile was tested at least once for 72 patients, and the diagnosis of CDP was established for 16 (10%) patients. All patients with CDP were symptomatic, 13 (81%) had diarrhea, 8 (50%) had abdominal pain, 7 (44%) had nausea/vomiting, and 2 (13%) had gastrointestinal bleeding. On multivariable analysis, only body mass index > 25 (OR 0.25, 95% CI 0.06-0.94, p = 0.048) was significantly associated with decreased risk of CDP. No patients in CDP cohort were admitted to ICU, died at the hospital, or readmitted in 30 days after the discharge. CONCLUSIONS: In our cohort, obesity was associated with low risk of CDP among hospitalized patients with pouchitis. This finding warrants further validation in prospective studies.

Mucosa-Associated Microbiota in Ileoanal Pouches May Contribute to Clinical Symptoms, Particularly Stool Frequency, Independent of Endoscopic Disease Activity.

INTRODUCTION: Pouchitis is a common complication after ileal pouch-anal anastomosis (IPAA). However, there is a poor correlation between symptoms and endoscopic appearance of the pouch, and many patients can have debilitating symptoms in the absence of overt inflammation. It is unknown whether these clinical symptoms are independently associated with the microbiota. The objective of this work was to examine whether the individual clinical components of the pouch activity scoring systems are associated with specific microbiota. METHODS: Pouch biopsies from 233 patients (50% male, 100% IPAA/ulcerative colitis) post-IPAA were included. Clinical phenotyping was performed, and patients were classified using both clinical and endoscopic components of the Pouch Activity Scale. Scoring for symptoms examined 24-hour stool frequency, urgency, incontinence, and rectal bleeding as described by the Pouchitis Disease Activity Index Score. RESULTS: In the absence of inflammation, an increase in stool frequency reported over 24 hours was associated with a decrease in Bacteroidetes relative abundance, and this was the strongest association found. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis in inflamed groups showed that an increase in 24-hour stool frequency was associated with an increase in biofilm formation. DISCUSSION: These findings indicate that in patients with IPAA, the composition of mucosa-associated microbiota of the pouch may contribute to clinical symptoms, particularly stool frequency, independent of endoscopic disease activity.

Systematic review: ileoanal pouch microbiota in health and disease.

BACKGROUND: The resident gut microbiota is essential for physiological processes; the disturbance of its balance is linked to intestinal inflammation. The ileoanal pouch is a model for the study of intestinal inflammation, as inflammation of the pouch is common and mostly develops within 12 months following ileostomy closure. This allows the longitudinal study of the microbiota, giving insight into the microbiota changes during transition from a normal to an inflamed pouch. AIM: To explore the literature on the microbiota of the ileoanal pouch in health and disease. METHODS: A systematic computer search of the on-line bibliographic databases MEDLINE and EMBASE was performed between 1966 and February 2017. Randomised controlled trials, cohort studies and observational studies were included. Studies were included if they reported microbiota analysis on faecal samples or tissue from the ileoanal pouch. RESULTS: Twenty-six papers were eligible. Following ileostomy closure, anaerobic bacteria are the abundant species in the ileoanal pouch with presence of a diverse microbiota key to maintaining a healthy ileoanal pouch. Acute pouchitis is associated with an increase in Clostridia species, while chronic pouchitis is associated with an increase in Staphylococcus aureus. In the treatment of pouchitis, a decrease in Clostridia species appears to be associated with treatment response. CONCLUSION: The microbiota plays an important role in both the inflamed and the healthy ileoanal pouch. A direct causal relationship between individual microbiota changes and inflammation has not yet been established, but manipulation of the ileoanal pouch microbiota may be a novel therapeutic avenue to explore.

Preoperative Clostridium difficile Infection Does Not Affect Pouch Outcomes in Patients with Ulcerative Colitis Who Undergo Ileal Pouch-anal Anastomosis.

BACKGROUND: The operation of choice for patients with chronic ulcerative colitis (CUC) is restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Pouchitis is the most common complication after IPAA. The incidence of Clostridium difficile infection (CDI) is higher in CUC patients than the general population and can lead to significant disease flares and higher rates of colectomy. We sought to determine the risk of pouchitis in patients with precolectomy CDI and 90-day postoperative IPAA complications. METHODS: A retrospective case-control study was conducted on patients with CUC who underwent an IPAA between January 1, 2000 and January 10, 2015. The study cohort was comprised of patients diagnosed with CDI within 90 days before colectomy; patients with CUC without CDI comprised the control cohort. The primary outcome measure was the frequency of pouchitis after IPAA. Secondary outcomes included time to pouchitis, 90-day postoperative pouch morbidity: surgical site infection, hemorrhage, anastomotic leak, fistula formation, pouchitis treatment and response, and pouch failure requiring end-ileostomy or fecal diversion. Univariate and multivariable analysis was used to determine differences between CDI and non-CDI groups. RESULTS: Forty-eight case patients and 154 control patients were included. Patients with preoperative CDI were younger (P = 0.010), had higher rates of medically refractory disease (P = 0.002), and had greater use of biologic therapy (P = 0.046). The rate of pouchitis was 50.0% (n = 24) and 46.8% (n = 72) (P = 0.694) among patients with and without preoperative CDI, respectively. Patients with preoperative CDI who developed pouchitis post-IPAA were more likely to require medical management with an anti-TNFα (P = 0.042) and surgical management with end/diverting ileostomy (P = 0.042). Preoperative CDI was associated with higher rates of postoperative IPAA anastamotic or pouch strictures (P = 0.018). Multivariable analysis revealed primary sclerosing cholangitis (PSC) as the only variable associated with increased risk for pouchitis (OR 10.59; 95% CI, 3.07-51.08; P < 0.001). CONCLUSIONS: Preoperative CDI does not seem to be associated with an increased risk of pouchitis in patients with CUC.

Patient-Specific Bacteroides Genome Variants in Pouchitis.

A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis). Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus, B. thetaiotaomicron, B. vulgatus, and B. fragilis, which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch. IMPORTANCE: This longitudinal study provides an opportunity to describe shifts in the microbiomes of individual patients who suffer from ulcerative colitis (UC) prior to and following inflammation. Pouchitis serves as a model for UC with a predictable incidence of disease onset and enables prospective longitudinal investigations of UC etiology prior to inflammation. Because of insufficient criteria for predicting which patients will develop UC or pouchitis, the interpretation of cross-sectional study designs suffers from lack of information about the microbiome structure and host gene expression patterns that directly correlate with the onset of disease. Our unique longitudinal study design allows each patient to serve as their own control, providing information about the state of the microbiome and host prior to and during the course of disease. Of significance to the broader community, this study identifies microbial strains that may have genetic elements that trigger the onset of disease in susceptible hosts.

Clostridium difficile infection after restorative proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis.

AIM: Clostridium difficile infection (CDI) of the ileal pouch following restorative proctocolectomy (RPC) is becoming increasingly recognized. We aimed to understand better (i) the associated risk factors, (ii) treatment practices and (iii) the pouch diversion and failure rate in patients who developed CDI of the pouch after RPC for ulcerative colitis (UC). METHOD: Patients who tested positive for C. difficile of the pouch between 2007 and 2010 were included in the analysis. Data collected included patient demographics, time from RPC to documented CDI, the treatment of CDI and rate of excision of the pouch. RESULTS: Of 2785 patients recorded in the hospital CDI database, 15 had had an RPC with ileal pouch anal anastomosis. The median age was 44 years and the median interval from RPC to first documented episode of CDI was 3 years. Thirteen (81%) patients had had multiple episodes of pouchitis before and after CDI infection, and all were symptomatic at the time of testing for CDI. Within 30 days of the diagnosis of CDI, six (40%) patients were taking immunosuppressive medication, seven (47%) were taking a proton pump inhibitor and 12 (80%) had received antibiotics. Five patients required hospitalization for CDI and four had severe infections characterized by a serum creatinine more than 1.5 times baseline (n = 3) and a white cell count above 15 000 (n = 1). Six patients who underwent endoscopy had severe inflammation of the pouch including the presence of a pseudomembrane in one case. Ten patients were treated with metronidazole alone and five with vancomycin. Two patients had recurrent CDI of the pouch during a median follow-up period of 2.9 years and one had CDI refractory to medical management. This patient required diversion of the pouch with an ileostomy for refractory CDI but no patient required excision of the pouch. CONCLUSION: All 15 patients developing CDI of the pouch were successfully treated with antibiotics and only one required surgery in the form of an ileostomy.

Microbiome Heterogeneity Characterizing Intestinal Tissue and Inflammatory Bowel Disease Phenotype.

Inflammatory bowel disease has been associated with differential abundance of numerous organisms when compared to healthy controls (HCs); however, few studies have investigated variability in the microbiome across intestinal locations and how this variability might be related to disease location and phenotype. In this study, we have analyzed the microbiome of a large cohort of individuals recruited at Mount Sinai Hospital in Toronto, Canada. Biopsies were taken from subjects with Crohn's disease, ulcerative colitis, and HC, and also individuals having undergone ileal pouch-anal anastomosis for treatment of ulcerative colitis or familial adenomatous polyposis. Microbial 16S rRNA was sequenced using the Illumina MiSeq platform. We observed a great deal of variability in the microbiome characterizing different sampling locations. Samples from pouch and afferent limb were comparable in microbial composition. When comparing sigmoid and terminal ileum samples, more differences were observed. The greatest number of differentially abundant microbes was observed when comparing either pouch or afferent limb samples to sigmoid or terminal ileum. Despite these differences, we were able to observe modest microbial variability between inflammatory bowel disease phenotypes and HCs, even when controlling for sampling location and additional experimental factors. Most detected associations were observed between HCs and Crohn's disease, with decreases in specific genera in the families Ruminococcaceae and Lachnospiraceae characterizing tissue samples from individuals with Crohn's disease. This study highlights important considerations when analyzing the composition of the microbiome and also provides useful insight into differences in the microbiome characterizing these seemingly related phenotypes.

Clostridium Difficile Infection in Ulcerative Colitis: Can Alteration of the Gut-associated Microbiome Contribute to Pouch Failure?

BACKGROUND: Ulcerative colitis is frequently treated with total proctocolectomy and ileal pouch-anal anastomosis reconstruction. Causes of pouch failure and criteria for improved patient selection remain poorly understood. We aimed to identify risk factors for pouch failure. METHODS: We performed a retrospective chart review of patients in a prospectively maintained database. Consecutive patients undergoing ileal pouch-anal anastomosis for inflammatory bowel disease between 2000 and 2010 at our institution were included. The primary outcome was pouch failure, defined as permanent ostomy diversion or pouch excision. RESULTS: Of 417 total patients, 28 (6.7%) patients developed pouch failure. Pouch failure was associated with female gender, anastomotic leak, Crohn's disease of the pouch and preoperative Clostridium difficile colitis. The use of anti-tumor necrosis factor alpha biologics was not associated with pouch failure. Notably, 14.9% of patients were diagnosed with preoperative C. difficile colitis, a factor independently associated with pouch failure (hazard ratio 3.02; 95% confidence interval, 1.23-7.44; P = 0.016). C. difficile colitis did not contribute to failure by increasing the incidence of anastomotic leak but was associated with a diagnosis of Crohn's disease of the pouch (adjusted hazard ratio 2.27 [1.08-4.79]; P = 0.031). Anastomotic leak (P < 0.001) and pelvic abscess requiring drainage (P = 0.031) were other independent risk factors for pouch failure. CONCLUSIONS: In addition to previously known risk factors, history of preoperative C. difficile colitis was associated with pouch failure after reconstruction, suggesting the need for further study into the role of the gut-associated microbiome in pouch outcomes.

The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis.

PURPOSE: Ulcerative colitis (UC) is a chronic, relapsing, and refractory disorder of the intestine. Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the preferred and standard surgical procedure for patients' refractory to medical therapy. Pouchitis is one of the most common long-term complications after IPAA. In the present study, the safety and efficacy of Clostridium butyricum MIYAIRI (CBM) as a probiotic were examined. METHODS: A randomized and placebo-controlled study was performed. Seventeen patients were recruited from 2007 to 2013. Nine tablets of MIYA-BM(®) or placebo were orally administered once daily. The cumulative pouchitis-free survival, pouch condition (using the modified pouch disease activity index), and blood parameters were evaluated. A fecal sample analysis was also performed. RESULTS: Subjects were randomly allocated to receive MIYA-BM or placebo (9 and 8 subjects, respectively). One subject in the MIYA-BM group and four subjects in the placebo group developed pouchitis. No side effects occurred in either group. Characteristic intestinal flora was observed in each group. CONCLUSIONS: Our results suggest that probiotic therapy with CBM achieved favorable results with minimal side effects and might be a useful complementary therapy for the prevention of pouchitis in patients with UC who have undergone IPAA.

Ileal pouch morphology and microbiology in ulcerative colitis patients.

BACKGROUND: Ideal pouch created during restorative proctocolectomy is a new gastrointestinal organ--"neorectum". Although it is made from the ileum, it takes over function of the removed rectum. This new function results in significant morphological changes in pouch's mucous membrane, which becomes similar to the large bowel mucosa. The most common pathology of the ileal pouch is its inflammation--pouchitis. One of the suspected causes of pouchitis is bacterial flora disturbance. OBJECTIVES: The aim of the study was to analyze the morphological and microbiological changes in ileal pouches in different time periods after ileostomy closure and to evaluate the influence of certain bacterial strains on the degree of inflammation. MATERIAL AND METHODS: The study involved 47 patients who had been treated surgically; they were investigated before and at different stages after ileostomy closure. They underwent repeated rectoscopies with biopsies of pouch mucosa and swabs for microbiological examination. In total 89 rectoscopies were performed, which provided 70 histopathological results according to the Heidelberg Pouchitis Activity Score and 87 microbiological test results. RESULTS: The assessment of the morphology of intestinal pouches showed increased signs of chronic inflammation as the length of time after the closure of a protective ileostomy increased. There was no correlation between the signs of acute inflammation and the length of time after surgery; there were more signs of acute inflammation in cases of pouchitis. The composition of the bacterial flora of intestinal pouches changed as the length of time after ileostomy closure increased, with significant increases in the number of enterobacteriaceae species. The presence of Staphylococcus aureus significantly correlates with a higher degree of chronic inflammation; this bacterium may be a potential infectious factor in pouchitis. CONCLUSIONS: Microbiological analysis of intestinal pouch lumen is a useful tool that can be used in routine follow-up assessment of intestinal pouches as well as in diagnosing pouchitis.

Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.

BACKGROUND: Pouchitis is common after ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC). Similar to inflammatory bowel disease (IBD), both host genetics and the microbiota are implicated in its pathogenesis. We use the IPAA model of IBD to associate mucosal host gene expression with mucosal microbiomes and clinical outcomes. We analyze host transcriptomic data and 16S rRNA gene sequencing data from paired biopsies from IPAA patients with UC and familial adenomatous polyposis. To achieve power for a genome-wide microbiome-transcriptome association study, we use principal component analysis for transcript and clade reduction, and identify significant co-variation between clades and transcripts. RESULTS: Host transcripts co-vary primarily with biopsy location and inflammation, while microbes co-vary primarily with antibiotic use. Transcript-microbe associations are surprisingly modest, but the most strongly microbially-associated host transcript pattern is enriched for complement cascade genes and for the interleukin-12 pathway. Activation of these host processes is inversely correlated with Sutterella, Akkermansia, Bifidobacteria, and Roseburia abundance, and positively correlated with Escherichia abundance. CONCLUSIONS: This study quantifies the effects of inflammation, antibiotic use, and biopsy location upon the microbiome and host transcriptome during pouchitis. Understanding these effects is essential for basic biological insights as well as for well-designed and adequately-powered studies. Additionally, our study provides a method for profiling host-microbe interactions with appropriate statistical power using high-throughput sequencing, and suggests that cross-sectional changes in gut epithelial transcription are not a major component of the host-microbiome regulatory interface during pouchitis.

Risk factors and management of refractory or recurrent clostridium difficile infection in ileal pouch patients.

BACKGROUND: Clostridium difficile infection (CDI) is increasingly recognized in patients with ulcerative colitis with ileal pouch-anal anastomosis (IPAA). The aim of this study was to identify clinical risk factors for treatment-refractory or recurrent CDI in patients with IPAA. METHODS: We identified patients with IPAA for underlying ulcerative colitis and a positive polymerase chain reaction stool test for C. difficile at the Center for Ileal Pouch Disorders during the period from October 2010 to November 2013. Demographic clinical variables were compared between the refractory or recurrent CDI and nonrecurrent CDI groups. RESULTS: Patients with IPAA with refractory or recurrent symptoms (refractory/recurrent CDI, the study group, N = 19) were compared with patients with a single antibiotic-responsive episode of ileal pouch CDI (nonrecurrent CDI, the control group, N = 21). The frequency of pouchitis before the index CDI was similar in the study and control groups (63.2% versus 66.7%, P = 0.82). Postoperative mechanical abnormalities occurred in 16 patients (84.2%) in the study group versus 7 patients (33.3%) in the control group (P = 0.0008). There were no differences between the two groups regarding hospitalization, non-C. difficile antibiotic use, the use of gastric acid-reducing therapy, or immunosuppressives before or after the index CDI. Six of 15 patients (40.0%) in the study group versus 1 of 15 patients (7.1%) in the control group had a low serum level of IgG1 (P = 0.031). CONCLUSIONS: Refractory or recurrent disease is common in patients with ileal pouch with CDI. The presence of postsurgery mechanical intestinal complications or low serum immunoglobulin level may be risk factors for refractory or recurrent CDI in this patient population.

Clostridium difficile infection in patients with ileal pouches.

Clostridium difficile (C. difficile) infection (CDI) following total proctocolectomy and ileal pouch-anal anastomosis has been increasingly recognized over the past 5 years. CDI of the ileal pouch has been recognized in ∼10% of symptomatic patients seen at a tertiary referral center for pouch dysfunction. In contrast to colonic CDI in the general population or in patients with inflammatory bowel disease, postoperative antibiotic exposure and the use of immunosuppressive agents or proton pump inhibitors do not appear to be associated with CDI of the pouch. Male gender, recent hospitalization, and presurgery antibiotic use were shown to be risk factors for ileal pouch CDI. The ileal pouch may be susceptible to CDI owing to similarities with the colon at physiological and structural levels. Postcolectomy CDI likely represents a spectrum of disease processes, varying from asymptomatic colonization to severe symptomatic infection. CDI should be considered in any patient with an ileal pouch presenting with a change in "normal" symptom pattern or treatment-refractory disease. Sensitive and specific methods for the detection of CDI are available, and pouchoscopy is a valuable tool in the evaluation of the patient with symptomatic CDI of the pouch. At a referral center for pouch dysfunction, vancomycin is used as the first-line therapy for ileal pouch CDI. Fecal microbiota transplantation may find use in the management of severe or antibiotic refractory CDI-related pouchitis.

Preoperative Clostridium difficile infection is not associated with an increased risk for the infection in ileal pouch patients.

BACKGROUND: Clostridium difficile infection (CDI) might contribute to a refractory course of pouchitis. However, the association between preoperative CDI and postoperative CDI in ileal pouch patients has not been investigated. AIM: Our study aimed to evaluate whether preoperative CDI had an impact on the occurrence of postoperative CDI in pouch patients. METHODS: Consecutive eligible ileal pouch patients from February 2005 to December 2012 were identified from the Pouchitis Registry at the Cleveland Clinic. Patients in the registry with known status of CDI of the pouch were surveyed with a structured questionnaire regarding preoperative C. difficile test and its treatment. Medical records were also reviewed. Demographics and clinical characteristics and outcomes were evaluated with univariable and multivariable analyses. RESULTS: A total of 102 patients with preoperative C. difficile test were identified for this study and 21 patients (20.6%) tested positive for C. difficile test after colectomy. In logistic regression analysis, male patients were 7.85 (P = 0.003) times more likely to have CDI than women. In addition, preoperative significant comorbidities (P = 0.037) and preoperative use antibiotics for other indications (P = 0.005) were found to be associated with postoperative CDI of the pouch. However, there was no evidence to suggest that the preoperative CDI was associated with the occurrence of postoperative CDI (P = 0.769). CONCLUSIONS: Postoperative CDI occurred frequently in male patients with IPAA. In addition, preoperative comorbidities and antibiotic use were found to be risk factors for CDI of the pouch. However, preoperative CDI did not appear to be associated with an increased risk for postoperative CDI in pouch patients.

The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis.

BACKGROUND: A total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. AIM: To examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. METHODS: Sixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and 5¹Cr-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. RESULTS: Pouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P < 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P < 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. CONCLUSIONS: Probiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.