141种肠道微生物群分类与14种风湿性疾病之间的因果关联：一项孟德尔随机化研究

Causal Associations Between 141 Gut Microbiota Taxa and 14 Rheumatic Diseases: A Mendelian Randomization Study.

作者信息

Hu Ying, He Hongyi, Zhang Yuqing, Lyu Houchen, Zeng Chao, Wei Jie, Lei Guanghua

机构信息

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Int J Rheum Dis. 2025 Jun;28(6):e70334. doi: 10.1111/1756-185X.70334.

DOI:10.1111/1756-185X.70334

PMID:40556359

Abstract

OBJECTIVE

Gut microbiota has been increasingly recognized as important and novel targets for rheumatic diseases. However, previous studies mainly examined the associations, leaving causality largely unknown. This knowledge gap hinders the application of gut microbiota in preventing and treating rheumatic diseases.

METHODS

We performed Mendelian randomization (MR) analysis to evaluate causal associations between gut microbiota and rheumatic diseases. Genetic instruments for 141 gut microbiota taxa were extracted from the published genome-wide association study (GWAS) (N = 18 340). Summary statistics for 14 rheumatic diseases were obtained from publicly available GWASs and the FinnGen database. The primary MR analysis employed the Wald ratio or inverse variance-weighted method, supported by additional MR approaches. Bi-directional MR and colocalization analyses were performed to test the reciprocal causality and investigate shared causal variants.

RESULTS

After multiple testing adjustments (FDR < 0.05), six pairs of relations remained statistically significant. Genus FamilyXIIIAD3011 group (odds ratio [OR] = 2.68, 95% CI = 2.35-3.07), class Deltaproteobacteria (OR = 1.37, 95% CI = 1.17-1.59), order Desulfovibrionales (OR = 1.36, 95% CI = 1.17-1.58), and family Desulfovibrionaceae (OR = 1.36, 95% CI = 1.17-1.58) increased the risk of ankylosing spondylitis (AS). Genus Eubacterium brachy group (OR = 0.56, 95% CI = 0.44-0.72) and order Mollicutes RF9 (OR = 0.60, 95% CI = 0.47-0.77) decreased the risk of gout. Additionally, class Deltaproteobacteria, family Desulfovibrionaceae, and order Desulfovibrionales shared the same genetic variants with AS. No evidence of bi-directional causality was observed.

CONCLUSION

We identified and provided genetic evidence for six novel causal associations between gut microbiota taxa with AS and gout. These findings open avenues for future research to investigate the impact of modulating these gut microbiota taxa on the prevention and treatment of AS and gout.

摘要

目的

肠道微生物群已日益被视为风湿性疾病重要的新靶点。然而，以往研究主要探讨了两者之间的关联，因果关系大多未知。这一知识空白阻碍了肠道微生物群在风湿性疾病防治中的应用。

方法

我们进行了孟德尔随机化（MR）分析，以评估肠道微生物群与风湿性疾病之间的因果关联。从已发表的全基因组关联研究（GWAS）（N = 18340）中提取了141种肠道微生物分类群的遗传工具变量。从公开可用的GWAS和芬兰基因数据库中获取了14种风湿性疾病的汇总统计数据。主要的MR分析采用了Wald比率或逆方差加权法，并辅以其他MR方法。进行了双向MR和共定位分析，以检验相互因果关系并研究共享的因果变异。

结果

经过多重检验校正（FDR < 0.05）后，六对关系仍具有统计学意义。XIIIAD3011菌群属（优势比[OR] = 2.68，95%可信区间[CI] = 2.35 - 3.07）、δ-变形菌纲（OR = 1.37，95% CI = 1.17 - 1.59）、脱硫弧菌目（OR = 1.36，95% CI = 1.17 - 1.58）和脱硫弧菌科（OR = 1.36，95% CI = 1.17 - 1.58）增加了强直性脊柱炎（AS）的发病风险。短真杆菌属（OR = 0.56，95% CI = 0.44 - 0.72）和柔膜菌纲RF9目（OR = 0.60，95% CI = 0.47 - 0.77）降低了痛风的发病风险。此外，δ-变形菌纲、脱硫弧菌科和脱硫弧菌目与AS共享相同的遗传变异。未观察到双向因果关系的证据。