Bile Acids Metabolism in Symptomatic Hand Osteoarthritis

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.

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.

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.

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.