Objectives: Ileal pouch anal anastomosis (IPAA), the removal of the colon and formation of a reservoir from ileum, is the surgery of choice for ulcerative colitis and familial adenomatous polyposis. Yet, 10 to 35% of patients develop pouchitis, an inflammation of the pouch mucosa. Microbial imbalances are observed in pouchitis and inulin has been suggested as a prebiotic treatment. Our objectives were to determine the effect of inulin supplementation on quality of life (QOL), and its practicality and safety as a treatment in IPAA patients.<p> Methods: Adults with IPAA (n= 8) consented to a blinded, placebo-controlled trial of inulin supplementation. Baseline symptoms were measured for 1 month prior to supplementation, followed by a blinded low-dose (5 g of inulin) or placebo (maltodextrin) for 2 weeks and a higher-dose (10 g) for 5.5 months. Participants recorded any symptoms that they experienced in a diary and QOL was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) at the beginning and end of the study.<p> Results: Two participants in the same group developed significant side effects on the 10 g supplementation; abdominal discomfort, severe gas, and small amounts of blood with defecation were reported. Unblinding determined that these participants were taking the active treatment (inulin); therefore, the study was stopped early. No differences were observed in SIBDQ scores.<p> Implications & Conclusions: In this pilot study, inulin appeared to be ineffective in improving QOL and may have contributed to unpleasant side effects. Future research should explore synbiotic therapy in IPAA, by combining prebiotics and probiotics for optimal results.

Objectives: Ileal pouch anal anastomosis (IPAA), the removal of the colon and formation of a reservoir from ileum, is the surgery of choice for ulcerative colitis and familial adenomatous polyposis. Yet, 10 to 35% of patients develop pouchitis, an inflammation of the pouch mucosa. Microbial imbalances are observed in pouchitis and inulin has been suggested as a prebiotic treatment. Our objectives were to determine the effect of inulin supplementation on quality of life (QOL), and its practicality and safety as a treatment in IPAA patients.<p> Methods: Adults with IPAA (n= 8) consented to a blinded, placebo-controlled trial of inulin supplementation. Baseline symptoms were measured for 1 month prior to supplementation, followed by a blinded low-dose (5 g of inulin) or placebo (maltodextrin) for 2 weeks and a higher-dose (10 g) for 5.5 months. Participants recorded any symptoms that they experienced in a diary and QOL was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) at the beginning and end of the study.<p> Results: Two participants in the same group developed significant side effects on the 10 g supplementation; abdominal discomfort, severe gas, and small amounts of blood with defecation were reported. Unblinding determined that these participants were taking the active treatment (inulin); therefore, the study was stopped early. No differences were observed in SIBDQ scores.<p> Implications & Conclusions: In this pilot study, inulin appeared to be ineffective in improving QOL and may have contributed to unpleasant side effects. Future research should explore synbiotic therapy in IPAA, by combining prebiotics and probiotics for optimal results.

Introduction: Inflammatory pouch complications, including pouchitis, chronic pouchitis (CP) and a Crohn’s disease-like phenotype (CDL) of the pouch following ileal pouch-anal anastomosis (IPAA), are relatively common, and arise via unknown mechanisms. The phenotypic similarities between pouch inflammation and inflammatory bowel disease (IBD) suggest there may be common pathways involved in both disorders. The aim of this thesis is to investigate the serological, genetic and microbial factors contributing to the development of pouch inflammation in a large, well characterized patient cohort. Methods: Subjects with IPAA were recruited, and clinical and demographic information was obtained through medical chart review and patient questionnaire, allowing patients to be grouped based on post-surgical phenotype. Blood and tissue was collected for genetic, serological and microbial analyses. Anti-microbial antibodies were detected using enzyme-linked immunosorbent assay (ELISA), genotyping was carried out using the Illumina Goldengate custom SNP assay and Sequenome iPLEX platform, and tissue-associated microbial communities were assessed using 454 pyrosequencing. Results: Among our cohort, smoking was associated with CDL (P=0.003) and Ashkenazi Jewish heritage with CP (P<0.008). NOD2insC (rs2066847) (P=7.4x10-5), anti-CBir1 (P<0.0001) and ASCA (IgG) (P=0.03) were significantly associated with inflammatory pouch outcomes. Additional SNPs in NOX3, DAGLB, and NCF4 were also marginally associated with pouch outcome. A multi-variable risk model combining clinical, serologic and genetic markers was constructed and could differentiate between chronic pouch inflammatory phenotypes and no pouchitis. Genus level microbial analysis demonstrated that several organisms (Bacteroides, Parabacteroides, Blautia and Moryella) were detected less frequently among the inflammatory outcome groups (P<0.05). These associations remained significant even following adjustment for antibiotic use, smoking, country of birth and gender. Conclusions: CD-associated anti-microbial antibodies and genetic markers are associated with chronic inflammatory pouch phenotypes. Additionally, changes in the composition of the pouch associated microbiome are associated with inflammation. These observations suggest that similar mechanisms may be involved in non-surgical IBD and pouchitis.

Background: Recent national trends and distribution of ileal pouch-anal anastomosis (IPAA) procedures for patients with ulcerative colitis (UC) are unknown. We examined the frequency of use of elective IPAA procedures among patients with UC and the distribution of IPAA procedures across more than 140 U.S. academic medical centers and their affiliates. Methods: Data were obtained from the University HealthSystem Consortium for patients with a primary diagnosis of UC admitted electively between 2012 and 2015. Results: The mean age of the study population (n=6,875) was 43 years and 57% were men. Among these, one-third (n=2,307) underwent an IPAA, while two-thirds (n=4,568) underwent colectomy, proctectomy, proctocolectomy or other procedures. The proportion of IPAA cases among all elective admissions was relatively stable at 33-35% during the years under study. A total of 131 hospitals, out of 279 hospitals participating in the UHC, performed IPAA. The median number of IPAA cases performed annually was 1.9 [IQR 0.8 – 4.3]. Nearly one half (48%) of these cases were performed by the top ten hospitals. Overall, only a total of 30 centers performed ³ five elective IPAA cases annually. Conclusions: Although the frequency of elective IPAA surgery in recent years has been stable, nearly one half of all IPAA cases was performed at ten hospitals. The concentration of IPAA cases at high-volume centers, and the steady number of cases performed annually, have potential implications for fellowship training, patient clinical outcomes and access to care.