Causal effects of gut microbiota on multiple sclerosis: A two-sample Mendelian randomization study

BackgroundGut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear.ObjectiveWe performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS.MethodsIndependent genetic variants associated with 211 gut microbiota phenotypes were selected as instrumental variables from the largest genome-wide association studies (GWAS) previously published by the MiBioGen study. GWAS data for MS were obtained from the International Multiple Sclerosis Genetics Consortium (IMSGC) for primary analysis and the FinnGen consortium for replication and collaborative analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy.ResultsAfter inverse-variance-weighted and sensitivity analysis filtering, seven gut microbiota with potential causal effects on MS were identified from the IMSGC. Only five metabolites remained significant associations with MS when combined with the FinnGen consortium, including genus Anaerofilum id.2053 (odds ratio [OR] = 1.141, 95% confidence interval [CI]: 1.021-1.276, p = .021), Ruminococcus2 id.11374 (OR = 1.190, 95% CI: 1.007-1.406, p = .042), Ruminococcaceae UCG003 id.11361 (OR = 0.822, 95% CI: 0.688-0.982, p = .031), Ruminiclostridium5 id.11355 (OR = 0.724, 95% CI: 0.585-0.895, p = .003), Anaerotruncus id.2054 (OR = 0.772, 95% CI: 0.634-0.940, p = .010).ConclusionOur MR analysis reveals a potential causal relationship between gut microbiota and MS, offering promising avenues for advancing mechanistic understanding and clinical investigation of microbiota-mediated MS. IVs: instrumental variables; SNP: single nucleotide polymorphism; MR: Mendelian randomization; up arrow: adverse effect; down arrow: protective effect. image