AKCCHF grant #00945 (closed)

Albert E Jergens, DVM, PhD, Iowa State University

Project Summary from AKCCHF.org website:

“Canine inflammatory bowel disease (IBD) is a chronic intestinal disorder likely resulting from the interaction between genes and environmental factors. We propose to utilize unique molecular biology tools to: (1) identify key genetic factors contributing to disease expression, (2) characterize gene expression profiles which may predict responsiveness to specific therapies, and (3) provide the framework upon which to facilitate identification of IBD susceptibility genes that predispose specific canine breeds to clinical disease.

We are making good progress towards these goals as evidenced by the following: We have collected samples from a representative heterogeneous population of 18 IBD dogs for comparison to 6 healthy dog tissues. We have carefully extracted the genetic material (RNA) from endoscopic samples which will be used in our gene profiling studies.  We have now evaluated gene expression profiles in the normal versus diseased dog groups using sophisticated statistical modeling to help us ‘tease out’ gene expression patterns which discern healthy versus diseased intestinal tissues. It is our expectation to identify specific genes which serve as biomarkers for diagnosing canine IBD and for monitoring the effects of therapy. We have now identified a grouping of 17 ‘marker’ genes that may be more critically assessed in future studies.  We have noted that IBD dogs show differences in intestinal gene expression as compared to healthy dogs; and these differences in expression may help to explain the mechanisms of chronic inflammation in affected dogs. We have preliminary evidence that changes in the intestinal bacteria accompany the abnormal gene patterns.

It is our belief that this association should be explored more fully with additional studies; since this situation is identical to the association between people and their intestinal bacterial populations causing human IBD (i.e., Crohn’s disease and ulcerative colitis). We have now confirmed the expression patterns of select differentially expressed genes in diseased dogs using sophisticated molecular techniques. This suggests that the observations regarding gene expression patterns using the gene chips are accurate.\”

Publications:

Suchodolski JS, Xenoulis PG, Paddock CG, Steiner JM and Jergens AE (2010) Molecular analysis of the bacterial microbiota in duodenal biopsies from dogs with idiopathic inflammatory bowel disease.Veterinary Microbiology. 142, 394-400.

Suchodolski JS, Dowd SE, Wilke V, Steiner JM, Jergens AE.  16S rRNA Gene Pyrosequencing Reveals Bacterial Dysbiosis in the Duodenum of Dogs with Idiopathic Inflammatory Bowel Disease.  2012.  PLoS One 7(6):e39333