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

Abstract

ABSTRACTBackgroundCrohn’s disease (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 (CAF), a disease with clinical similarities to fistulizing CD, as a surrogate model for human fistulizing CD.ResultsBy comparing the gut microbiomes between dogs suffering from CAF (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 dog’s microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance ofBacteroides vulgatusandEscherichia coliand a decreased abundance ofMegamonasspecies andPrevotella copri. These same determinant bacteria are associated with human CD.ConclusionsOur 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.