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Abstract：
BACKGROUND: Gut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear.
OBJECTIVE: We performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS.
METHODS: Independent 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.
RESULTS: After 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).
CONCLUSIONS: Our 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.
OBJECTIVE: We performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS.
METHODS: Independent 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.
RESULTS: After 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).
CONCLUSIONS: Our 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.
摘要：
背景：观察性研究报道了多发性硬化症（MS）患者的肠道菌群改变，但这些关联是否是因果关系尚不清楚.
目的：我们进行了孟德尔随机研究（MR），以评估肠道菌群对MS的因果影响。
方法：选择与211种肠道微生物群表型相关的独立遗传变异作为工具变量，这些变量来自之前由MiBioGen研究发表的最大的全基因组关联研究(GWAS)。MS的GWAS数据从国际多发性硬化遗传学协会(IMSGC)获得用于初级分析,并且从FinnGen协会获得用于复制和协作分析。进行敏感性分析以评估异质性和多效性。
结果：经过逆方差加权和敏感性分析过滤，从IMSGC中确定了7种对MS具有潜在因果影响的肠道微生物群。当与FinnGen联盟结合时，只有五种代谢物与MS保持显著关联，包括厌氧菌属id.2053(比值比[OR]=1.141，95%置信区间[CI]：1.021-1.276，p=.021)，Ruminococus2id.11374（OR=1.190，95%CI：1.007-1.406，p=0.042），RuminocycaceaeUCG003id.11361（OR=0.822，95％CI：0.688-0.982，p=0.031），Ruminiclostridium5id.11355（OR=0.724，95%CI：0.585-0.895，p=.003），anaerotruncusid.2054（OR=0.772，95%CI：0.634-0.940，p=.010）。
结论：我们的MR分析揭示了肠道菌群与MS之间的潜在因果关系，为推进微生物群介导的MS的机械理解和临床研究提供了有希望的途径。
目的：我们进行了孟德尔随机研究（MR），以评估肠道菌群对MS的因果影响。
方法：选择与211种肠道微生物群表型相关的独立遗传变异作为工具变量，这些变量来自之前由MiBioGen研究发表的最大的全基因组关联研究(GWAS)。MS的GWAS数据从国际多发性硬化遗传学协会(IMSGC)获得用于初级分析,并且从FinnGen协会获得用于复制和协作分析。进行敏感性分析以评估异质性和多效性。
结果：经过逆方差加权和敏感性分析过滤，从IMSGC中确定了7种对MS具有潜在因果影响的肠道微生物群。当与FinnGen联盟结合时，只有五种代谢物与MS保持显著关联，包括厌氧菌属id.2053(比值比[OR]=1.141，95%置信区间[CI]：1.021-1.276，p=.021)，Ruminococus2id.11374（OR=1.190，95%CI：1.007-1.406，p=0.042），RuminocycaceaeUCG003id.11361（OR=0.822，95％CI：0.688-0.982，p=0.031），Ruminiclostridium5id.11355（OR=0.724，95%CI：0.585-0.895，p=.003），anaerotruncusid.2054（OR=0.772，95%CI：0.634-0.940，p=.010）。
结论：我们的MR分析揭示了肠道菌群与MS之间的潜在因果关系，为推进微生物群介导的MS的机械理解和临床研究提供了有希望的途径。
