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Causal Link Between Gut Microbiota and Arterial Occlusive Diseases: Insights From Mendelian Randomization and
1Department of Vascular Surgery, General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Background:
Arterial occlusive diseases (AOD), including peripheral artery disease (PAD), are significant causes of morbidity and mortality worldwide. Emerging evidence suggests that gut microbiota may play a crucial role in the pathogenesis of PAD. However, causal relationships remain unclear due to limitations in observational studies.
Aims:
This study aims to investigate the causal relationship between gut microbiota and PAD.
Methods:
This study employed a two-sample Mendelian randomization (MR) approach using genome-wide association study (GWAS) summary statistics to investigate the causal relationship between gut microbiota and PAD. Genetic variants associated with gut microbiota were used as instrumental variables. Sensitivity analyses were performed to assess pleiotropy and heterogeneity, and results were validated in independent datasets.
Results:
We identified significant causal associations between specific gut microbiota and PAD. Notably, Candidatus Soleaferrea and Ruminococcaceae UCG005 were positively associated with PAD risk. Validation analyses across diverse populations confirmed the robustness of these associations. Pathway enrichment analysis highlighted potential mechanisms, including inflammatory and metabolic pathways such as TNF signaling and AMPK signaling pathway.
Conclusion:
This study provides strong evidence of a causal relationship between gut microbiota and AOD, particularly PAD. The findings highlight the potential of gut microbiota as biomarkers and therapeutic targets in managing vascular diseases. Further research is warranted to explore microbiota-targeted interventions and their clinical applications.
Insights
This study used Mendelian randomization to find a causal link between gut bacteria and peripheral artery disease (PAD). Specific bacteria like Candidatus Soleaferrea and Ruminococcaceae UCG005 increase PAD risk, suggesting new therapeutic targets.
Area of Science:
- Microbiology
- Genetics
- Vascular Biology
Background:
- Arterial occlusive diseases (AOD), including peripheral artery disease (PAD), are major global health burdens.
- Gut microbiota is increasingly implicated in PAD pathogenesis, but causal links require elucidation.
Purpose of the Study:
- To investigate the causal relationship between gut microbiota and peripheral artery disease (PAD).
- To identify specific gut microbial taxa causally associated with PAD risk.
Main Methods:
- Utilized a two-sample Mendelian randomization (MR) approach.
- Employed genome-wide association study (GWAS) summary statistics for gut microbiota and PAD.
- Conducted sensitivity analyses and validated findings in independent datasets.
Main Results:
- Identified significant causal associations between specific gut microbes and PAD.
- Found positive associations between Candidatus Soleaferrea and Ruminococcaceae UCG005 with PAD risk.
- Highlighted inflammatory and metabolic pathways (e.g., TNF, AMPK signaling) as potential mechanisms.
Conclusions:
- Provides robust evidence for a causal role of gut microbiota in PAD.
- Suggests gut microbiota as potential biomarkers and therapeutic targets for vascular diseases.
- Warrants further research into microbiota-targeted interventions for PAD management.
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