Idiopathic inflammatory bowel disease (IBD) is characterized by intestinal mucosal inflammation and is associated with alterations in the gut microbiome or intestinal dysbiosis. Treatment is directed at the pathophysiologic mechanisms and often includes dietary modification, antibiotics, and/or immunosuppressants. Treatment responses are often suboptimal, and relapses are common, making management of IBD a challenge. Intestinal dysbiosis is present at the time of diagnosis in dogs with IBD, however changes in the microbiome over time in dogs undergoing standard immunosuppresssive therapy have not been well characterized. The purpose of this study was to evaluate longitudinal changes of the intestinal microbiome in dogs with IBD being treated with prednisone.
Thirteen dogs diagnosed with idiopathic IBD, that previously failed to respond to treatment with elimination diets and metronidazole, were enrolled. Stool samples were collected from all dogs before initiating therapy with prednisone, after 3 and 8 weeks, and more than one year after beginning treatment. Thirteen healthy dogs were enrolled in the study as a control group. Stool samples were kept frozen at -80oC until DNA extraction. The microbiota was characterized using Illumina sequencing of 16S rRNA genes. Data were analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Beta diversity was evaluated with the phylogeny based unweighted UniFrac distance metric, and statistics were performed with the Analysis of Similarities (ANOSIM).
In the IBD group, clinical disease severity (CIBDAI) at baseline was scored as moderate to severe. All dogs achieved partial or complete remission of clinical signs by 3 or 8 weeks of treatment, and CIBDAI scores were significantly reduced after 8 weeks of treatment (p < 0.001). At baseline, dogs with IBD showed differences in microbial composition when compared to healthy dogs, as unweighted UniFrac distances demonstrated significantly different beta diversity between groups (p=0.001, R=0.462). Differences in the IBD group included increased Firmicutes (p < 0.001) and Actinobacteria (p=0.027), and reduced Bacteroidetes (p < 0.001), Fusobacteria (p < 0.001) and Proteobacteria (p=0.006). Within the IBD group, beta diversity was still significantly changed at 8 weeks (p < 0.001) compared to healthy controls. At the 1 year follow up, diversity metrics placed the microbiome of treated dogs closer to that of healthy dogs, but they were still significantly different from those of healthy controls (p=0.003, R=0.258).
Our results suggest that, while treatment can be effective in improving clinical signs, the dysbiosis associated with IBD is still present after more than one year after the initiation of immunosuppressive therapy, even when dogs were clinically well controlled.
Post Doctoral Research Associate
Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX.
Thursday, June 14
3:00 PM – 3:15 PM
Thursday, June 14
3:15 PM – 3:30 PM
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