Abstract
ABSTRACT Crohn’s disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance toward the commensal microbiota. On average, 29.5% and 42.7% CD patients experience perianal complications at 10 and 20 y after diagnosis, respectively. Perianal CD (pCD) result in high disease burden, diminished quality of life, and elevated health-care costs. Overall pCD are predictors 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 pCD, as a surrogate model for understanding the microbial contribution of human pCD pathophysiology. By comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show CAF-dog microbiomes are either very dissimilar (dysbiotic) or similar (healthy-like), yet unique, to healthy dog’s 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. Our results mirror what have been reported in previous microbiome studies of patients with CD; particularly, CAF dogs exhibited two distinct microbiome composition: dysbiotic and healthy-like, with determinant bacterial taxa such as E. coli and P. copri that overlap what it has been found on their human counterpart. Thus, our results support the use of CAF dogs as a surrogate model to advance our understanding of microbial dynamics in pCD.
Highlights
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD), are immune-mediated inflam matory condition affecting more than a million indi viduals in the US
Several genetic variants have been associated with increased risk of development of Perianal CD (pCD), PRDM1, NOD2, and ATG16L1.4,5 Immunologically, patients with pCD exhibit an upregulated expression of TNF-α compared to CD patients without perianal complications or healthy controls.[6]
When we analyzed differences in microbial composition between dogs according to their disease status, we found slightly lower alpha diversity in canine anal furunculosis (CAF) dogs compared to healthy control dogs (HC dogs) (Figure 1A, Shannon diversity, Kruskal–Wallis test, p value = .06), similar to previous results with IBD dogs.[46]
Summary
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD), are immune-mediated inflam matory condition affecting more than a million indi viduals in the US. The etiology of pCD is not well defined yet is thought to be a combination of genetic and immune factors, and the microbiome. Several genetic variants have been associated with increased risk of development of pCD, PRDM1, NOD2, and ATG16L1.4,5 Immunologically, patients with pCD exhibit an upregulated expression of TNF-α compared to CD patients without perianal complications or healthy controls.[6] The role of the microbiome has gained attention in recent years as evidence indicating its involvement emerges.[7,8,9] treatment with antibiotics (reviewed in2,10), fecal diversion,[7,8] and fecal transplants[9] have proven to be effective for managing the disease. We aim to evaluate the usefulness of dogs as a model system to elucidate the contribution of the microbiota to the pathophysiology of pCD
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