Causal relationship between hydrogen sulfide and osteoarthritis: A Mendelian randomization analysis

Hydrogen sulfide (H 2 S) has been shown to alleviate bone and joint inflammation in osteoarthritis (OA). Exploring the connection between H 2 S and OA could reveal novel therapeutic avenues for treating this condition. This study utilized H 2 S as the exposure variable and OA as the outcome within a Mendelian randomization framework. Data for genome-wide association studies related to both exposure and outcome were sourced from the IEU OpenGWAS project. To estimate causal relationships, inverse variance weighted method was employed, along with supplementary analytical techniques (MR-Egger, weighted median, simple mode, and weighted mode), and sensitivity studies were carried out to evaluate our results’ dependability. The inverse variance weighted analysis revealed that the abundance of a specific gut bacterial pathway involved in the reduction process of sulfate “SO4ASSIM.PWY..sulfate.reduction.I..assimilatory.” acts as a protective factor against hospital-diagnosed knee osteoarthritis, with an odds ratio of 0.687 (95% confidence interval = 0.479–0.987, P = .042). In contrast, gut bacterial pathway abundance associated with sulfate assimilation and cysteine biosynthesis “SULFATE.CYS.PWY..superpathway.of.sulfate.assimilation.and.cysteine.biosynthesis” was linked to increased risk for hospital-diagnosed OA, showing an odds ratio value of 1.120 (95% confidence interval = 1.000–1.255, P = .049). Sensitivity analyses validated the strength of the causal relationship between the gut bacterial pathway abundance and OA. We identified that the gut bacterial pathway abundance associated with H 2 S “SO4ASSIM.PWY..sulfate.reduction.I..assimilatory.” acts as a protective factor for OA suggesting its potential role in OA treatment and offering new avenues for research on H 2 S in the treatment of OA in this context.