Bile Acids Metabolism in Symptomatic Hand Osteoarthritis

OBJECTIVE: Although gut microbiome dysbiosis is associated with symptomatic hand osteoarthritis (SHOA), the role of bile acids (BAs), key metabolites in host-microbiota interactions, in SHOA pathogenesis remains unexplored. We investigated the association between plasma BA metabolism and SHOA. METHODS: The associations between plasma BAs and SHOA were examined in the Xiangya Osteoarthritis (XO) Study and validated in an independent cohort through logistic regression models. Gut microbiome data from a previous study conducted within the XO Study were integrated to explore associations between SHOA-related gut microbes and key BAs. As an exploratory analysis, gene-based meta-analyses evaluated associations between genes encoding key BA receptors and hand OA. RESULTS: In the discovery cohort (n = 1,359, mean age ± SD 63.1 ± 9.0 years, 58.4% women, SHOA prevalence 5.2%, all participants being Asian), elevated levels of deoxycholic acid (DCA) species (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.96) and DCA (OR 2.14, 95% CI 1.24-3.70) were positively associated with SHOA presence and severity. These associations were replicated in an independent cohort (n = 142). Multiomics analyses revealed significant correlations of DCA species, DCA, and the DCA species-to-total BAs ratio with SHOA-related gut microbes. DCA interacted with SHOA-related gut microbes and was associated with SHOA. Gene-based meta-analyses identified significant associations between genes encoding the Farnesoid X receptor and the pregnane X receptor and hand OA. CONCLUSION: Dysregulated BA metabolism, particularly elevated DCA levels, is associated with SHOA. The observation that DCA interacts with SHOA-related gut microbes, together with genes encoding DCA receptors, may help guide future biologically and clinically relevant studies.