Association between gut microbiome-related metabolites and symptomatic hand osteoarthritis in two independent cohortsResearch in context

Summary: Background: Since gut microbiome dysbiosis can cause inflammatory disorders by affecting host metabolism, we postulate that the gut microbiome and related metabolites could play a role in hand osteoarthritis. We characterised gut microbiome-related metabolites in people with symptomatic hand osteoarthritis (SHOA) in two independent cohorts. Methods: Using data collected from a large-sample community-based observational study (discovery cohort), we assessed the relations of the microbial function and plasma key metabolites related to altered microbial function with SHOA. Finally, we verified the relations of plasma metabolites to SHOA in an independent observational study (validation cohort). Findings: In the discovery cohort (n = 1359), compared to those without SHOA, participants with SHOA had significantly altered microbial functions related to tryptophan metabolism (Q = 0.025). Therefore we measured the plasma tryptophan metabolites and found that participants with SHOA had higher levels of 5-hydroxyindoleacetic acid (odds ratio [OR] = 1.25, 95% confidence interval [CI]: 1.09–1.42) and 5-hydroxytryptophol (OR = 1.13, 95% CI: 1.04–1.23), but lower levels of indole-3-lactic acid (ILA) (OR = 0.85, 95% CI: 0.72–1.00), skatole (OR = 0.93, 95% CI: 0.88–0.99) and 3-hydroxyanthranilic acid (OR = 0.90, 95% CI: 0.85–0.96). Findings from the validation cohort (n = 142) verified that lower levels of ILA were related to SHOA (OR = 0.70, 95% CI: 0.53–0.92). Interpretation: Alterations of the microbial function of tryptophan biosynthesis and tryptophan metabolites, especially lower levels of ILA, are associated with SHOA. These findings suggest the role of the microbiome and tryptophan metabolites in developing of SHOA and may contribute to future translational opportunities. Funding: National Key Research and Development Plan and National Natural Science Foundation of China.