Genetic support of the causal association between gut microbiota and peripheral artery disease: a bidirectional Mendelian randomization study

Aging (Albany NY). 2024 Jan 9;16(1):762-778. doi: 10.18632/aging.205417. Epub 2024 Jan 9.


Background: The causal relationship between gut microbiota and peripheral artery disease (PAD) is still not clear. In this research, we employed the Mendelian randomization (MR) technique to explore the potential causal connection between 211 gut microbiota species and PAD. We also investigated whether the causal effects operate in both directions.

Methods: We used Genome-wide Association Studies (GWAS) summary statistics data from the MiBioGen and FinnGen consortia to conduct a two-sample MR analysis to explore the causal link between gut microbiota and PAD. Sensitivity analysis is conducted to assess the robustness of the MR results. In addition to that, reverse MR analysis was performed to examine the inverse causal relationship.

Results: The inverse variance weighted (IVW) method provided evidence supporting a causal relationship between 9 specific gut microbiota taxa and PAD. The study findings indicated that family Family XI (OR=1.11, CI 1.00-1.24, P=0.048), genus Lachnoclostridium (OR=1.24, 1.02-1.50, P=0.033), and genus Lachnospiraceae UCG001 (OR=1.17, 1.01-1.35, P=0.031) are risk factors associated with PAD. class Actinobacteria (OR=0.84, 0.72-0.99, P=0.034), family Acidaminococcaceae (OR=0.80, 0.66-0.98, P=0.029), genus Coprococcus2 (OR=0.79, 0.64-0.98, P=0.029), genus Ruminococcaceae UCG004 (OR=0.84, 0.72-0.99, P=0.032), genus Ruminococcaceae UCG010 (OR=0.74, 0.58-0.96, P=0.022), and order NB1n (OR=0.88, 0.79-0.98, P=0.02) may be associated with the risk factors of PAD. Moreover, our analysis did not uncover any evidence of a reverse causal relationship between PAD and the nine specific gut microbiota taxa investigated.

Conclusions: Our MR research has confirmed the potential causal relationship between gut microbiota and PAD while also identifying specific gut bacterial communities associated with PAD.

Keywords: Mendelian randomization; causal effect; genetic association; gut microbiota; peripheral artery disease.

MeSH terms

  • Causality
  • Gastrointestinal Microbiome* / genetics
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Peripheral Arterial Disease* / genetics