MicroRNAs and Host-Gut Microbe Interactions in Canine Chronic Enteropathy

Presentation Description / Summary: Canine chronic enteropathy (CE) denotes a group of intestinal disorders characterized by persistent GI signs and variable intestinal inflammation. Accumulating evidence links microbial imbalances (dysbiosis) to intestinal inflammation in affected dogs. MicroRNAs (miRNAs) are small non-encoding RNAs that regulate gene expression at the post-transcriptional level. The miRNAs secreted by intestinal epithelial cells are released into the gut lumen where they modulate the growth and composition of the intestinal microbiota, including their secretion of metabolites. The gut microbiome in the host can be influenced by diet derived miRNAs also, while the intestinal microbiota in turn regulates the expression of miRNAs produced by intestinal epithelial cells of the host. Aberrant miRNA expression and intestinal dysbiosis are strongly correlated with chronic intestinal diseases, especially IBD and colorectal cancer in people. Studies in experimental animal models and IBD patients indicate that miR-194, miR-148, and miR-27 are strongly correlated with gut inflammation and increased fecal abundance of Proteobacteria. Collectively, the scientific evidence in people indicates an interconnected relationship (crosstalk) among miRNAs, intestinal microbiota, diet, and intestinal immunity in regulating homeostasis or dysbiosis of the GI environment. A single report suggests the presence of dysregulated miRNAs in colonic tissues and sera of dogs with large intestinal IBD. This presentation will provide a comprehensive overview on the role of miRNAs in the pathogenesis of CE in dogs, as well as report results from a recently completed clinical trial investigating the association between miRNAs, mucosal microbiota, and host response to treatment interventions.

Learner Outcomes: 1. What are miRNAs and how do they mediate mucosal homeostasis to maintain gut health 2. What factors influence miRNA expression in health and disease - roles for dysbiosis and diet in disease pathogenesis 3. How does sequential therapy (diet, glucocorticoids, probiotics) modulate miRNA expression and indices of remission in dogs with CE 3.