Distinct microbiome in pouchitis compared to healthy pouches in ulcerative colitis and familial adenomatous polyposis

Authors

  • Garrett C. Zella MD,

    Corresponding author
    1. Division of Pediatric Gastroenterology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
    • Division of Pediatric Gastroenterology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge St. 5th Fl., Boston, MA 02114
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  • Elizabeth J. Hait MD, MPH,

    1. Children's Hospital Boston, Division of Gastroenterology and Nutrition, Boston, Massachusetts
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  • Tiffany Glavan BA,

    1. University of California, Davis, Department of Medical Microbiology and Immunology, Davis, California
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  • Dirk Gevers PhD,

    1. Microbial Sequencing Center, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
    2. Laboratory of Microbiology, Gent University, Gent, Belgium
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  • Doyle V. Ward PhD,

    1. Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
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  • Christopher L. Kitts PhD,

    1. Environmental Biotechnology Institute, Biological Sciences Department, California Polytechnic State University, San Luis Obispo, California
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  • Joshua R. Korzenik MD

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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Abstract

Background:

Pouchitis occurs in up to 50% of patients with ulcerative colitis (UC) undergoing ileal pouch anal anastomosis (IPAA). Pouchitis rarely occurs in patients with familial adenomatous polyposis (FAP) who undergo IPAA. Our aim was to compare mucosal and luminal flora in patients with UC-associated pouchitis (UCP), healthy UC pouches (HUC), and healthy FAP pouches (FAP).

Methods:

Nineteen patients were enrolled in this cross-sectional study (nine UCP, three HUC, seven FAP). Patients with active pouchitis were identified using the Pouchitis Disease Activity Index (PDAI). Ileal pouch mucosal biopsies and fecal samples were analyzed with a 16S rDNA-based terminal restriction fragment length polymorphism (TRFLP) approach. Pooled fecal DNA from four UCP and four FAP pouches were sequenced for further speciation.

Results:

TRFLP data revealed statistically significant differences in the mucosal and fecal microbiota between each group of patients. UCP samples exhibited significantly more TRFLP peaks matching Clostridium and Eubacterium genera compared to HUC and FAP pouches and fewer peaks matching Lactobacillus and Streptococcus genera compared to FAP. DNA Sanger sequencing of a subset of luminal samples revealed UCP having more identifiable sequences of Firmicutes (51.2% versus 21.2%) and Verrucomicrobia (20.2% versus 3.2%), and fewer Bacteroidetes (17.9% versus 60.5%) and Proteobacteria (9.8% versus 14.7%) compared to FAP.

Conclusions:

The pouch microbial environment appears to be distinctly different in the settings of UC pouchitis, healthy UC, and FAP. These findings suggest that a dysbiosis may exist in pouchitis which may be central to understanding the disease. (Inflamm Bowel Dis 2010;)

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