The indigenous microbiota of the gastrointestinal tract is the richest of the human- associated microbial communities in terms of absolute biomass and relative diversity. Although the gut microbiota play critical roles in the maintenance of gut homeostasis, evidence is accumulating that disturbances in the gut microbial community ("dysbiosis") underlie a number of gastrointestinal disease states including antibiotic-associated diarrhea and inflammatory bowel disease (IBD). To address our hypothesis we propose to determine the relationship between the gut microbiome and the development of mucosal inflammation in patients with ulcerative colitis. We will coordinate and integrate existing resources for the study of IBD patients, metagenomic analysis, molecular microbial diversity analysis and targeted sequence-aided bacterial culture into a research pipeline for the study of complex host-associated microbial communities. We will characterize the gut microbiota in human patients who have undergone total colectomy with the construction of an ileal pouch anal anastomosis for treatment of ulcerative colitis. These patients will be followed temporally after surgery to monitor for the development of mucosal inflammation in the pouch anastomosis ("pouchitis"). Comparison within patients over time and between patients will be done to associate specific ecologic and functional characteristics of the gut microbiome with the development of pouchitis. To accomplish these goals, we have assembled an experienced, integrated team of researchers from a variety of disciplines. We will study a carefully selected group of patients with ulcerative colitis that will permit us to make inter- and intra-patient comparisons over time. Though the use of high-throughput, cost- effective technologies, which members of this team have played a key role in developing, we intend to demonstrate a critical role for the gut microbiome in the development of the dysregulated mucosal immune response that is the hallmark of IBD. This knowledge will lead the way to novel ways to monitor patients with IBD and to the development of novel preventative and therapeutic interventions.

Public Health Relevance

The bacteria that live in the gut are felt to play a key role in the health of the gastrointestinal tract. We will determine the role of the gut bacteria in the development of human inflammatory bowel disease through the use of state-of-the-art molecular biology techniques and advanced culture techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
Project #
5UH3DK083993-04
Application #
8308650
Study Section
Special Emphasis Panel (ZRG1-IDM-A (52))
Program Officer
Karp, Robert W
Project Start
2009-06-24
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$2,570,040
Indirect Cost
$244,202
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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