Microbial Gene Profiling and Targeted Metabolomics in Fecal Samples of Dogs With Chronic Enteropathy With or Without Increased Dysbiosis Index

Background: In previous studies, only a subset of dogs with chronic enteropathy (CE) had an increased dysbiosis index (DI) or altered fecal metabolites or both, suggesting differences in underlying intestinal pathophysiology between these subsets. Objectives: To compare microbial functional genes and fecal metabolites between healthy dogs with DI < 0 (HC) and dogs with CE and DI > 0 (increased DI-CE) or DI < 0 (normal DI-CE). Animals: Retrospective cross-sectional study including 78 HC and 138 CE dogs. Methods: Fecal microbiome was assessed by DNA shotgun sequencing. Dysbiosis index was quantified by qPCR. Targeted fecal metabolites, long-chain fatty acids, sterols, bile acids (BAs), and carbohydrates were measured using gas chromatography–mass spectrometry (GC–MS). Results: In permutational analysis of variance (PERMANOVA), functional gene profiles showed larger shifts in increased DI-CE (median R2 [95% confidence interval (CI)] = 0.12 [0.08–0.17]) than normal DI-CE (0.02 [0.01–0.04]) compared with HC (adjusted-p < 0.02), characterized by increased counts of carbohydrate and lipid degradation genes. Similarly, increased DI-CE (PERMANOVA, median R2 [95% CI] = 0.23 [0.14–0.34]) had larger shifts in fecal metabolome than normal DI-CE (0.10 [0.04–0.20]; adjusted-p < 0.02). Increased DI-CE had lower fecal unconjugated secondary BAs percentage (95% CI; HC, 88.4%–96.4%; normal DI-CE, 79.8%–99.0%; increased DI-CE, 28.1%–64.1%) and transporter-independent carbohydrates (combined ribose, xylose, rhamnose, and arabinose) concentrations (1.6–2.6; 0.7–1.8; 0.3–1.3 ng/mg; adjusted-p < 0.01). Conclusions: Results indicate differences in fecal microbial gene profiles and metabolome in increased DI-CE versus normal DI-CE and HC, suggesting dogs with an increased DI have more severe intestinal changes in metabolic functions.