Causal relationship between gut microbiota and muscular dystrophy: A Mendelian randomization analysis

Muscular dystrophy (MD) encompasses a group of inherited muscle diseases characterized by progressive muscle weakness and degeneration. While emerging research suggests that gut microbiota may contribute to the development of systemic diseases, its causal impact on MD remains uncertain. This study aims to investigate the causal relationship between gut microbiota and MD using Mendelian randomization (MR) analysis. A 2-sample MR analysis was conducted using gut microbiota as the exposure and MD as the outcome. Gut microbiota data were obtained from a European cohort with 412 microbial taxa (n = 7738), while MD data were sourced from the Finnish biobank (n = 4,53,733). The primary analysis was performed using inverse variance weighted method, with additional sensitivity tests including leave-one-out analysis, Cochran's Q test for heterogeneity, and MR-Egger regression for horizontal pleiotropy. Nineteen single nucleotide polymorphisms significantly associated with gut microbiota were identified as instrumental variables. The inverse variance weighted analysis revealed that Desulfovibrionaceae (odds ratio [OR] = 2.751, 95% confidence interval [CI]: 1.261-5.999) and Lachnospiraceae (OR = 2.214, 95% CI: 1.135-4.315) were significantly associated with increased MD risk, whereas Clostridiales showed a protective effect (OR = 0.322, 95% CI: 0.126-0.820). Sensitivity analyses and funnel plots did not indicate significant bias or pleiotropy. This study provides the first evidence of a potential causal relationship between Desulfovibrionaceae, Lachnospiraceae, and increased MD risk, while Clostridiales may have a protective role. These findings suggest that gut microbiota modulation could be a novel therapeutic strategy for MD management.