Long-Term Recovery of the Fecal Microbiome and Metabolome of Dogs with Steroid-Responsive Enteropathy

SIMPLE SUMMARY: The impact of treatment of dogs with steroid-responsive enteropathy (a form of chronic diarrhea that responds to treatment with a corticosteroid) on the intestinal microbiome (the collection of all microorganisms in the GI tract) and metabolome (the collection of all small molecules produced by the microbiome or the host) was investigated in this study. Dogs receiving standard treatment were evaluated before (week 0), during (week 3), and at the end of treatment (week 8), as well as 1 year later, in comparison to healthy control dogs. None of the dogs had clinically relevant signs of disease at the end of treatment. While both the microbiome and the metabolome normalized to some degree after treatment, some key bacteria and many molecules remained different, suggesting that certain abnormalities persisted. However, 1 year after treatment, both the microbiome and the metabolome were no longer different from healthy dogs, suggesting that intestinal recovery from chronic steroid-responsive enteropathy takes longer than resolution of clinical signs would suggest. ABSTRACT: The long-term impact of treatment of dogs with steroid-responsive enteropathy (SRE) on the fecal microbiome and metabolome has not been investigated. Therefore, this study aimed to evaluate the fecal microbiome and metabolome of dogs with SRE before, during, and following treatment with standard immunosuppressive therapy and an elimination diet. We retrospectively selected samples from 9 dogs with SRE enrolled in a previous clinical trial, which received treatment for 8 weeks, and had achieved remission as indicated by the post-treatment clinical scores. Long-term (1 year) samples were obtained from a subset (5/9) of dogs. Samples from 13 healthy dogs were included as controls (HC). We evaluated the microbiome using 16S rRNA sequencing and qPCR. To evaluate the recovery of gut function, we measured fecal metabolites using an untargeted approach. While improvement was observed for some bacterial taxa after 8 weeks of treatment, several bacterial taxa remained significantly different from HC. Seventy-five metabolites were altered in dogs with SRE, including increased fecal amino acids and vitamins, suggesting malabsorption as a component of SRE. One year after treatment, however, all bacterial species were evaluated by qPCR and 16S rRNA gene sequencing, and all but thirteen metabolites were no longer different from healthy controls.