Omic tools applied to elucidation of the role of intestinal microbiota in the remission of Inflammatory Bowel Disease (IBD) based on therapeutic diet

Abstract

The healthy human gut 'microbiome' constitutes an ecosystem of microbes that play an essential role in maintaining health and the microbiome composition shifts in response to several factors, including diet. For example, during Inflammatory Bowel Disease (IBD) the overall diversity of the microbiome declines and treatment restores diversity. Although laboratory mouse models have been instrumental in identifying mechanisms underlying IBD, mice do not exhibit clinical heterogeneity in IBD symptoms or response to treatment, making them a poor model for this aspect of human disease. We propose to study the microbioma of dogs with canine chronic enteropathy (CCE), a spontaneous inflammatory intestinal disease that recapitulates human disease. The research group of the supervisor abroad (Dr. Beiting at Pennsylvania University) has conducted a trial with dogs that entered in remission of CCE after therapeutic diet and, the main goal of this project is to analyze fecal samples of the animals before and after treatment, to identify possible changes in the intestinal microbiome and also, changes in the metabolites in body fluids (metabolomics). We postulate that the analysis of the microbiome following treatment in both responding and non-responding individuals will allow for the identification of "protective" bacteria or "opportunistic" bacteria that drive disease progression. While such studies would be challenging and expensive to carry out in humans, they are relatively inexpensive and can be rigorously controlled in dogs, providing important insight into the role of the microbiome in IBD. This proposal is both technically and conceptually innovative, since it applies cutting-edge metagenomics to study an animal model of spontaneous IBD during treatment-induced remission. The involvement of a mentoring team with expertise in human IBD enhances the translational potential of the work, and it is an aspect of that would only be possible at an institution like the UPenn, where a world-leading veterinary hospital, adult human hospital and children's hospital are all within a few blocks of each other.For the near future, these studies may contribute for the development of potential probiotics for treatment of IBD.