Causal associations between 26 musculoskeletal disorders and gut microbiota: A Mendelian randomization analysis with Bayesian validation

Emerging evidence suggests that gut microbiota imbalances may influence the onset of musculoskeletal disorders (MSDs), yet conclusive evidence establishing causation remains limited. This study investigates the causal relationship between gut microbiota and a range of MSDs, aiming to identify potential therapeutic targets. Using data on 211 gut microbiome taxa from a genome-wide association study (GWAS) and summary statistics for 26 MSDs from the Finnish Biobank, we employed Mendelian randomization (MR) with inverse-variance weighting (IVW) as the primary analytical approach, complemented by Bayesian model validation to ensure robust results. Our MR analyses revealed significant causal associations between gut microbiota and nine MSDs within four categories, including osteoporosis (IVW-Beta = 0.011, P = 0.025), rheumatoid arthritis (IVW-Beta = -0.016, P < 0.001), rotator cuff syndrome (IVW-Beta = -0.007, P = 0.022), and calcific tendonitis of the shoulder (IVW-Beta = -0.021, P = 0.034). Bayesian validation underscored the plausibility of these relationships, supporting the potential causal role of gut microbiota in the development of these disorders. Our findings present a library of causal associations that underscore the gut microbiome's role in MSD pathogenesis, providing genetic evidence that highlights specific gut microbiota taxa as prospective therapeutic targets. This research offers novel insights into the pathogenic mechanisms underlying MSDs and points toward new directions for future investigation into microbiome-based therapies.