Longitudinal assessment of microbial dysbiosis, fecal unconjugated bile acid concentrations, and disease activity in dogs with steroid‐responsive chronic inflammatory enteropathy

Abstract

Background Mounting evidence from human studies suggests that bile acid dysmetabolism might play a role in various human chronic gastrointestinal diseases. It is unknown whether fecal bile acid dysmetabolism occurs in dogs with chronic inflammatory enteropathy (CE). Objective To assess microbial dysbiosis, fecal unconjugated bile acids (fUBA), and disease activity in dogs with steroid‐responsive CE. Animals Twenty‐four healthy control dogs and 23 dogs with steroid‐responsive CE. Methods In this retrospective study, fUBA were measured and analyzed. Fecal microbiota were assessed using a dysbiosis index. The canine inflammatory bowel disease activity index was used to evaluate remission of clinical signs. This was a multi‐institutional study where dogs with steroid‐responsive CE were evaluated over time. Results The dysbiosis index was increased in dogs with CE (median, 2.5; range, −6.2 to 6.5) at baseline compared with healthy dogs (median, −4.5; range, −6.5 to −2.6; P = .002) but did not change in dogs with CE over time. Secondary fUBA were decreased in dogs with CE (median, 29%; range, 1%‐99%) compared with healthy dogs (median, 88%; 4%‐96%; P = .049). The percent of secondary fUBA in dogs with CE increased from baseline values (median, 28%; range, 1%‐99%) after 2‐3 months of treatment (median, 94%; range, 1%‐99%; P = 0.0183). Conclusions and Clinical Importance These findings suggest that corticosteroids regulate fecal bile acids in dogs with CE. Additionally, resolution of clinical activity index in dogs with therapeutically managed CE and bile acid dysmetabolism are likely correlated. However, subclinical disease (i.e., microbial dysbiosis) can persist in dogs with steroid‐responsive CE.

The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease

“…The DI is the first tool that allows quantification of gut dysbiosis, and can be used to monitor dysbiosis over time and in response to treatment. Other studies have since confirmed that DI is increased in dogs with CE (26,27,82).…”

“…Interestingly, one of the Clostridiaceae strains was later identified as Clostridium hiranonis, a bacterial species associated with normal bile acid (BA) metabolism (25,26). A study (23) reported normal BA metabolism in healthy dogs fed BARF diets, with no significant difference from kibble-fed controls.…”

“…A study (23) reported normal BA metabolism in healthy dogs fed BARF diets, with no significant difference from kibble-fed controls. BA metabolism is an important pathway not only for lipid digestion, but also for regulation of intestinal inflammation, and is commonly altered in chronic gastrointestinal diseases (26,27).…”

“…Intestinal inflammation can also be triggered by gut dysbiosis through bile acid dysmetabolism, which is seen both in dogs and in humans (26,27,58). Bile acids (BA) are essential for lipid digestion, but also play a role in mucosal defenses and have anti-inflammatory properties.…”

“…In one study (84), although all dogs recovered clinically, the diversity indices after 3 weeks of therapy showed a trend toward a further decrease. Another study evaluated recovery of bile acid metabolism and DI over 3 months, and, while BA metabolism was restored and C. hiranonis significantly increased, other relevant species and the overall DI were still significantly altered (26).…”