Dysbiosis in a canine model of human fistulizing Crohn's disease

Background: Crohn9s disease or CD is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance towards the commensal microbiota. Approximately 70% of CD patients experience perianal complications. Perianal fistulizing is a predictor of poor long term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis or CAF, a disease with clinical similarities to fistulizing CD, as a surrogate model for human fistulizing CD. Results: By comparing the gut microbiomes between dogs suffering from CAF or CAF dogs and healthy dogs, we show that similar to microbiome population trends in CD humans, CAF dogs microbiomes are either very dissimilar (dysbiotic), or similar, yet unique, to healthy dogs microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance of Bacteroides vulgatus and Escherichia coli and a decreased abundance of Megamonas species and Prevotella copri. These same determinant bacteria are associated with human CD. Conclusions: Our results highlight the similarities in microbiome community patterns between CAF dogs and CD humans, including overlapping determinant bacterial taxa, and support the use of CAF dogs as a surrogate model to study human fistulizing CD.