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Causal Associations Between 141 Gut Microbiota Taxa and 14 Rheumatic Diseases: A Mendelian Randomization Study
Ying Hu1, Hongyi He2, Yuqing Zhang3,4
1Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.
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.
Insights
This study used Mendelian randomization to find causal links between gut bacteria and rheumatic diseases. Certain gut microbes were found to increase the risk of ankylosing spondylitis and decrease the risk of gout.
Area of Science:
- Microbiome research
- Rheumatic disease genetics
- Causal inference
Background:
- Gut microbiota is increasingly recognized as a factor in rheumatic diseases.
- Previous studies focused on associations, leaving causality undetermined.
- Understanding causality is crucial for developing microbial-targeted therapies for rheumatic conditions.
Purpose of the Study:
- To investigate the causal associations between gut microbiota and rheumatic diseases using Mendelian randomization.
- To identify specific gut bacteria that may causally influence the risk of developing ankylosing spondylitis (AS) and gout.
- To explore potential shared genetic factors between gut microbiota and rheumatic diseases.
Main Methods:
- Mendelian randomization (MR) analysis was performed.
- Genetic instruments for 141 gut microbiota taxa were used.
- Genome-wide association study (GWAS) data for 14 rheumatic diseases were analyzed.
Main Results:
- Six statistically significant causal associations were identified after multiple testing adjustments.
- Increased risk of ankylosing spondylitis (AS) was associated with the genus FamilyXIIIAD3011 group, class Deltaproteobacteria, order Desulfovibrionales, and family Desulfovibrionaceae.
- Decreased risk of gout was associated with the genus Eubacterium brachy group and order Mollicutes RF9.
- Shared genetic variants were found between AS and Deltaproteobacteria, Desulfovibrionaceae, and Desulfovibrionales.
Conclusions:
- This study provides genetic evidence for novel causal relationships between specific gut microbiota and ankylosing spondylitis (AS) and gout.
- The identified gut microbiota taxa represent potential targets for future therapeutic interventions.
- Further research into modulating these gut microbes could lead to new strategies for preventing and treating AS and gout.
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