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Principal Investigator: Kenneth Simpson
Contact Information: Email: kws5@cornell.edu - Phone: 607-253-3251
Sponsor: Morris Animal Foundation
Grant Number: DO6CA-038
Title: Defining the Role of Mucosa-Associated Bacterial Flora in Inflammatory Bowel Disease
Annual Direct Cost: $31,946
Project Period: 01/01/07-12/31/09
DESCRIPTION (provided by applicant): Inflammatory bowel disease (IBD) is a significant problem in small animal practice. However, little is known about its etiology, and treatment is usually based on empirical combinations of diet, antimicrobials and immunosuppression.
Research in people and experimental animals strongly suggests that IBD is caused by an overly aggressive inflammatory response to a subset of commensal enteric bacteria in genetically predisposed individuals. Increased mucosal colonization and invasion by bacteria appears to play a pivotal role in driving local and systemic inflammation. Studies of the intestinal microflora of dogs with IBD have focused on the identification of potential pathogens or their toxins in feces (e.g. Clostridium spp.) or duodenal juice (e.g. German Shepherd dogs), but fail to explain the clinical response to antibiotics observed in subsets of dogs with IBD.
We propose to investigate the relationship of mucosa-associated bacteria to the local and systemic inflammatory response, and clinical outcome in dogs with IBD. The mucosa-associated flora will be evaluated by microbial culture, and contemporary culture-independent techniques. The local and systemic inflammatory response will be measured using real time qPCR for mucosal cytokine mRNA, and circulating C-reactive protein. Presence and severity of clinical signs and response to treatment will establish the clinical outcome/phenotype.
By elucidating the inter-relationships of mucosa-associated bacteria, local and systemic inflammatory responses and clinical outcome, we hope to directly relate pathophysiology to patient care, and to provide evidence to guide treatment with antibiotics, probiotics or prebiotics, directed at modulating or displacing mucosa-associated bacteria, and dampening mucosal and systemic inflammation.
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