Translational Biomedical Research 2012 Seminar Series

Kenneth Simpson, Ph.D.

3/27/2012  8:00 am

Monday, April 23, 2012 • NOON - 1 PM
Room 612 Institute for Genomic Biology
1206 W. Gregory Drive, Urbana

The Microbiota and Chronic Enteropathies

Inflammatory bowel disease (IBD) is the term applied to a group of poorly understood enteropathies that commonly affect animals and people. IBD in both people and animals is increasingly considered a consequence of uncontrolled intestinal inflammation in response to a combination of elusive environmental, enteric luminal constituents (principally microbial and dietary) and immunoregulatory factors in genetically susceptible individuals.

In people, genetic susceptibility is linked increasingly to defects in innate immunity exemplified by mutations in the innate immune receptor NOD2/CARD15, that in the presence of the enteric microflora may lead to up-regulated mucosal cytokine production, delayed bacterial clearance and increased bacterial translocation, thereby promoting and perpetuating intestinal inflammation. While the mucosa-associated flora is implicated frequently as a pivotal factor in the development of IBD in people and animals, the specific bacterial characteristics that drive the inflammatory response have remained elusive. Recent advances in molecular microbiology have enabled the analysis of complex bacterial communities without bacterial culture. The application of these culture independent techniques to people, dogs and cats with gastrointestinal disease has revealed that intestinal inflammation is typically associated with a floral shift from Gram-positive to Gram-negative bacteria, predominantly Enterobacteriaceae. It is noteworthy that increased numbers of Enteobacteriaceae have been found to correlate with mucosal inflammation and clinical signs in cats with signs of gastrointestinal disease, and a novel group of adherent and invasive E. coli (AIEC) have been associated with intestinal inflammation in people and Boxer dogs with granulomatous colitis. In many patients it remains to be determined if these floral alterations are a cause or a consequence of the inflammation, but their discovery has provided new opportunities for therapeutic intervention. This is exemplified by intramucosal E. coli in Boxer dogs with GC, where eradication of invasive E. coli correlates with long term clinical and histological remission.

This presentation will give an in depth overview of the mucosal microflora associated with chronic intestinal inflammation in dogs, cats and people, and data from murine models that reveal acute inflammation can also perturb the enteric microbiota, and trigger the proliferation of adherent and invasive E. coli similar to those described in IBD.

 

 Kenneth Simpson 

Kenneth Simpson, PhD
Professor of Medicine
College of Veterinary Medicine
Cornell University

Dr. Simpson received a B.V.M.&S. in Veterinary Medicine from Royal Dick School of Veterinary Studies, University of Edinburgh, UK, in 1984. He obtained his Ph.D. (1989) in Veterinary Medicine from the University of Leicester, UK. Dr. Simpson completed his Veterinary Internal Medicine Residency (1991) at the College of Veterinary Medicine, Ohio State University, Columbus, OH, and was a Small Animal Medicine lecturer at the University of Leicester (1991-1995). He joined the faculty at the College of Veterinary Medicine, Cornell University in 1995, where he is currently Professor of Medicine in the College of Veterinary Medicine.

 

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