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

Area of Science:

• Genetics
• Microbiology
• Biochemistry

Background:

• Osteoarthritis (OA) is a debilitating joint disease with limited treatment options.
• Hydrogen sulfide (H2S) has demonstrated anti-inflammatory properties relevant to bone and joint health.
• Investigating the link between H2S and OA pathogenesis may uncover novel therapeutic targets.

Purpose of the Study:

• To explore the causal relationship between hydrogen sulfide (H2S) related gut bacterial pathways and osteoarthritis (OA) using a Mendelian randomization approach.
• To identify specific microbial metabolic pathways influencing OA risk.
• To assess the potential of H2S-associated microbial pathways as therapeutic targets for OA.

Main Methods:

• Mendelian randomization analysis utilizing genome-wide association study (GWAS) data from the IEU OpenGWAS project.
• Inverse variance weighted (IVW) method as the primary analytical tool, supplemented by MR-Egger, weighted median, simple mode, and weighted mode.
• Sensitivity analyses were performed to ensure the robustness and reliability of the findings.

Main Results:

• The abundance of the gut bacterial pathway 'SO4ASSIM.PWY..sulfate.reduction.I..assimilatory.', associated with H2S production, was found to be a protective factor against hospital-diagnosed knee OA (OR=0.687, P=0.042).
• Conversely, the gut bacterial pathway 'SULFATE.CYS.PWY..superpathway.of.sulfate.assimilation.and.cysteine.biosynthesis' was associated with an increased risk of hospital-diagnosed OA (OR=1.120, P=0.049).
• Sensitivity analyses confirmed the significant causal associations between these gut bacterial pathways and OA.

Conclusions:

• Specific gut bacterial pathways involved in sulfate reduction and H2S metabolism play a significant role in the risk of developing osteoarthritis.
• 'SO4ASSIM.PWY..sulfate.reduction.I..assimilatory.' pathway demonstrates a protective effect, suggesting its therapeutic potential in OA.
• These findings highlight the gut microbiome's influence on OA and open new avenues for H2S-based therapeutic research in OA treatment.