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

Abstract

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. 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. We 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 themore » 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. The 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.« less

Authors:

Young, Vincent B. ^[1]; Raffals, Laura H. ^[2]; Huse, Susan M. ^[3]; Vital, Marius ^[4]; Dai, Dongjuan ^[4]; Schloss, Patrick D. ^[1]; Brulc, Jennifer M. ^[5]; Antonopoulos, Dionysios A. ^[5]; Arrieta, Rose L. ^[6]; Kwon, John H. ^[6]; Reddy, K. Gautham ^[6]; Hubert, Nathaniel A. ^[6]; Grim, Sharon L. ^[3]; Vineis, Joseph H. ^[3]; Dalal, Sushila ^[6]; Morrison, Hilary G. ^[3]; Eren, A. Murat ^[3]; Meyer, Folker ^[5]; Schmidt, Thomas M. ^[4]; Tiedje, James M. ^[4] more »; Chang, Eugene B. ^[6]; Sogin, Mitchell L. ^[3] « less

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+ Show Author Affiliations

1. University of Michigan, Ann Arbor, MI (United States)
2. Mayo Clinic, Rochester, MN (United States)
3. Marine Biological Laboratory, Woods Hole, MA (United States)
4. Michigan State University, East Lansing, MI (United States)
5. Argonne National Laboratory (ANL), Argonne, IL (United States)
6. University of Chicago, IL (United States)

Publication Date:

Mon Mar 04 00:00:00 EST 2013

Research Org.:

Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Leona M. and Harry B. Helmsley Foundation; Crohn’s and Colitis Foundation of America Award

OSTI Identifier:

1626687

Grant/Contract Number:  

AC02-06CH11357; UH2/3 DK083993; P30 DK42086; R01 HG005975

Resource Type:

Accepted Manuscript

Journal Name:

Microbiome

Additional Journal Information:

Journal Volume: 1; Journal Issue: 1; Journal ID: ISSN 2049-2618

Publisher:

BioMed Central

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; pouchitis; microbiome; microbial ecology; inflammatory bowel disease