Patient-Specific Bacteroides Genome Variants in Pouchitis.

Joseph H Vineis,Hilary G Morrison,Eugene B Chang,Mitchell L Sogin,Laura H Raffals,David T Rubin,Sushila Dalal,Dionysios A Antonopoulos,Tom O Delmont,A Murat Eren,Daina L Ringus

doi:10.1128/mbio.01713-16

Joseph H Vineis, Hilary G Morrison + Show 9 more

Open Access

https://doi.org/10.1128/mbio.01713-16

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Abstract

ABSTRACTA 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.

Highlights

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
Based upon the pouch disease activity index, 9 patients developed pouchitis at least once during the 2-year study period (p_patients), 10 patients never developed pouch inflammation (n_patients), and 3 patients (p-500, p-502, and p-215) developed pouchitis after completion of the study. This 2-year longitudinal study included 96 luminal content samples acquired at different time points after functionalization of the ileal pouch (Fig. 1) from inflammatory bowel diseases (IBD) patients during visits where they exhibited inflammation (I samples), during visits where they did not exhibit inflammation (W samples), and approximately 30 days following antibiotic treatment prescribed for pouchitis (A samples)
Thirty-nine of the luminal samples came from surgically created pouches that never became inflamed throughout the duration of the study (N samples), and a brush sampling procedure recovered microbes acquired from three mucosal samples (GG sampling site) during periods of inflammation after pouch functionalization

Summary

Introduction

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). Because clinicians lack criteria for predicting the onset of UC, cross-sectional studies that compare UC patients with individuals presumed to be healthy cannot unambiguously attribute shifts in microbial communities or altered host gene expression patterns to initial inflammation events. The assembly of shotgun metagenomic reads into contigs and assembled genomes have the potential to report differences in rapidly evolving genomic regions of closely related organisms Such differences might represent horizontal gene transfers between Bacteroides, including genes that specify capsular polysaccharide (CPS) biosynthesis [9], which can either stimulate or suppress an immune response [10,11,12,13], and conjugative transposons that mobilize toxin genes [14]

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