Characterization of the Gut-Associated Microbiome in Inflammatory Pouch Complications Following Ileal Pouch-Anal Anastomosis

Abstract

IntroductionInflammatory complications following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) are common and thought to arise through mechanisms similar to de novo onset inflammatory bowel disease. The aim of this study was to determine whether specific organisms in the tissue-associated microbiota are associated with inflammatory pouch complications.MethodsPatients having previously undergone IPAA were recruited from Mount Sinai Hospital. Clinical and demographic information were collected and a pouchoscopy with biopsy of both the pouch and afferent limb was performed. Patients were classified based on post-surgical phenotype into four outcome groups: familial adenomatous polyposis controls (FAP), no pouchitis, pouchitis, and Crohn’s disease-like (CDL). Pyrosequencing of the 16S rRNA V1-V3 hypervariable region, and quantitative PCR for bacteria of interest, were used to identify organisms present in the afferent limb and pouch. Associations with outcomes were evaluated using exact and non-parametric tests of significance.ResultsAnalysis at the phylum level indicated that Bacteroidetes were detected significantly less frequently (P<0.0001) in the inflammatory outcome groups (pouchitis and CDL) compared to both FAP and no pouchitis. Conversely, Proteobacteria were detected more frequently in the inflammatory groups (P=0.01). At the genus level, organisms associated with outcome were detected less frequently among the inflammatory groups compared to those without inflammation. Several of these organisms, including Bacteroides (P<0.0001), Parabacteroides (P≤2.2x10-3), Blautia (P≤3.0x10-3) and Sutterella (P≤2.5x10-3), were associated with outcome in both the pouch and afferent limb. These associations remained significant even following adjustment for antibiotic use, smoking, country of birth and gender. Individuals with quiescent disease receiving antibiotic therapy displayed similar reductions in these organisms as those with active pouch inflammation.ConclusionsSpecific genera are associated with inflammation of the ileal pouch, with a reduction of typically ubiquitous organisms characterizing the inflammatory phenotypes.

Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC

“…In the present study, Blautia spp numbers were also reduced in faecal samples of patients with pouchitis 1 year after IPAA. A recent study also reported lower levels of Blautia species in patients with pouchitis compared with patients with NP 59. Collectively, these findings suggest that monitoring Blautia spp after IPAA might be useful to discriminate between inflamed pouches and NPs.…”

Inflammatory Bowel Disease as a Model for Translating the Microbiome

“…As a cross-sectional diagnostic indicator for IBD, colonic microbial profiles provide only modest delineation between patients and asymptomatic controls (Dicksved et al, 2008; Frank et al, 2007; Morgan et al, 2012), ruling out a simple, universal “magic bullet” for early diagnosis, although optimistically this need not be the case in all complex inflammatory conditions. Instead, heterogeneity among CD, UC, and subtypes within them (e.g., ileal CD) suggests that carefully chosen microbial samples could, for example, be used to improve classification under high-risk conditions such as ileal pouch surgery (Tyler et al, 2013). …”

Microbiota as Therapeutic Targets

“…To date, profiling of colonic microbial communities have not yielded robust results as a cross-sectional diagnostic indicator for IBD [34,36,59], although the heterogeneous nature of CD and UC raise the possibility that mindfulness of disease subtypes may help improve classification of certain groups (e.g. individuals who experience inflammatory pouch complications following ileal pouch-anal anastomosis) [60]. Treatment response prediction also remains an attractive, but relatively unexplored, potential use of microbial profiling.…”