Multiphasic analysis of the temporal development of the distal gut microbiota in patients following ileal pouch anal anastomosis

Vincent B Young ,Sushila Dalal,Dongjuan Dai,Marius Vital,Folker Meyer,James M Tiedje ,Sharon L Grim ,Laura H Raffals ,Patrick D Schloss ,K Gautham Reddy ,Hilary G Morrison ,Rose Arrieta ,Dionysios A Antonopoulos ,A Murat Eren ,Thomas M Schmidt ,Nathaniel Hubert ,Jennifer M Brulc ,John H Kwon ,Joseph H Vineis ,Eugene B Chang ,Susan M Huse ,Mitchell L Sogin

doi:10.1186/2049-2618-1-9

Abstract

BackgroundThe indigenous gut microbiota are thought to play a crucial role in the development and maintenance of the abnormal inflammatory responses that are the hallmark of inflammatory bowel disease. Direct tests of the role of the gut microbiome in these disorders are typically limited by the fact that sampling of the microbiota generally occurs once disease has become manifest. This limitation could potentially be circumvented by studying patients who undergo total proctocolectomy with ileal pouch anal anastomosis (IPAA) for the definitive treatment of ulcerative colitis. A subset of patients who undergo IPAA develops an inflammatory condition known as pouchitis, which is thought to mirror the pathogenesis of ulcerative colitis. Following the development of the microbiome of the pouch would allow characterization of the microbial community that predates the development of overt disease.ResultsWe monitored the development of the pouch microbiota in four patients who underwent IPAA. Mucosal and luminal samples were obtained prior to takedown of the diverting ileostomy and compared to samples obtained 2, 4 and 8 weeks after intestinal continuity had been restored. Through the combined analysis of 16S rRNA-encoding gene amplicons, targeted 16S amplification and microbial cultivation, we observed major changes in structure and function of the pouch microbiota following ileostomy. There is a relative increase in anaerobic microorganisms with the capacity for fermentation of complex carbohydrates, which corresponds to the physical stasis of intestinal contents in the ileal pouch. Compared to the microbiome structure encountered in the colonic mucosa of healthy individuals, the pouch microbial community in three of the four individuals was quite distinct. In the fourth patient, a community that was much like that seen in a healthy colon was established, and this patient also had the most benign clinical course of the four patients, without the development of pouchitis 2 years after IPAA.ConclusionsThe microbiota that inhabit the ileal-anal pouch of patients who undergo IPAA for treatment of ulcerative colitis demonstrate significant structural and functional changes related to the restoration of fecal flow. Our preliminary results suggest once the pouch has assumed the physiologic role previously played by the intact colon, the precise structure and function of the pouch microbiome, relative to a normal colonic microbiota, will determine if there is establishment of a stable, healthy mucosal environment or the reinitiation of the pathogenic cascade that results in intestinal inflammation.

Highlights

The indigenous gut microbiota are thought to play a crucial role in the development and maintenance of the abnormal inflammatory responses that are the hallmark of inflammatory bowel disease
Our study is unique in examining the relationship of the microbiota and pouchitis and offers several advantages: (1) a clearly defined starting point when all patients are free of disease and off medications, (2) the opportunity to observe the development of a nascent pouch microbiota relative to the maturation of the ileal pouch, (3) sampling of mucosa-associated pouch microbiota without colonic lavage [21] and (4) the identification of pouch microbial communities that may be associated with health or increased risk of disease
Our sample size was small, our findings suggest that the failure to develop a mature microbial community similar to that found in the healthy colon in the months following ostomy closure increases susceptibility to pouchitis

Summary

Introduction

The indigenous gut microbiota are thought to play a crucial role in the development and maintenance of the abnormal inflammatory responses that are the hallmark of inflammatory bowel disease. Direct tests of the role of the gut microbiome in these disorders are typically limited by the fact that sampling of the microbiota generally occurs once disease has become manifest. This limitation could potentially be circumvented by studying patients who undergo total proctocolectomy with ileal pouch anal anastomosis (IPAA) for the definitive treatment of ulcerative colitis. The singular localization of these diseases suggests that topical or regional factors are important in their development In this regard, indigenous enteric microbes may play an important role, as they have been strongly implicated in the etiopathogenesis of inflammatory bowel diseases [1,2,3,4]

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