Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 12: 1606 - 1619

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.12.006

Evidence-based medicine

Causal relationship between gut microbiota and cardiovascular diseases: a bidirectional Mendelian randomization analysis

  • MA Huihua ,
  • YAN Kuipo ,
  • LIU Gang ,
  • XU Yazhou ,
  • ZHANG Lei ,
  • SUN Yanqin
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  • 1.Heart Center National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China
    2.The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou 450000, China
YAN Kuipo, E-mail: ykp19821122@163.com.

Received date: 2025-04-17

  Accepted date: 2025-06-17

  Online published: 2025-12-28

Supported by

Henan Province Specialized Research Fund for Traditional Chinese Medicine Science(2016ZY3003,2021JDZX038,2017ZY2017)

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Abstract

Objective ·To investigate the causal relationship between gut microbiota and cardiovascular diseases (CVDs) using Mendelian randomization (MR). Methods ·Instrumental variables included genetic loci from gut microbiota data provided by the MiBioGen consortium (n=18 340) and CVD data from the IEU Open GWAS database, covering four CVD types: atrial fibrillation (n=1 030 836), coronary artery disease (n=547 261), hypertension (n=20 526), and heart failure (n=977 323). The inverse variance weighted (IVW) method was employed as the primary analytical approach. Additionally, Cochran's Q test was used to assess heterogeneity of genetic instruments, the MR-Egger intercept test to evaluate horizontal pleiotropy, and leave-one-out analysis to examine the sensitivity of single-nucleotide polymorphisms (SNPs) on the exposure-outcome causal relationship. The MR Steiger test was applied to validate the causal direction between gut microbiota and CVDs. Results ·The IVW analysis indicated that Victivallales (OR=0.939), Howardella (OR=0.939), Anaerostipes (OR=0.922), Bifidobacteriaceae (OR=0.916), Lentisphaeria (OR=0.936), Odoribacter (OR=0.909), Intestinibacter (OR=0.933), Lentisphaerae (OR=0.926), and Bifidobacteriales (OR=0.916) were protective factors against atrial fibrillation, while Catenibacterium (OR=1.057), Lachnospiraceae UCG008 (OR=1.051), Streptococcus (OR=1.089), and Victivallis (OR=1.038) were risk factors. For coronary artery disease, Lactobacillales (OR=0.919) and Parabacteroides (OR=0.866) were protective factors, while Veillonellaceae (OR=1.065), Lachnoclostridium (OR=1.093), Lachnospiraceae (OR=1.094), Oxalobacter (OR=1.062), and Odoribacter (OR=1.160) were risk factors. For hypertension, Mollicutes RF9 (OR=0.851), Coriobacteriia (OR=0.803), Coriobacteriales (OR=0.803), Coriobacteriaceae (OR=0.803), and Intestinibacter (OR=0.819) were protective factors, while Christensenellaceae R7 group (OR=1.218), Desulfovibrio (OR=1.167) ,and Peptococcaceae (OR=1.230) were risk factors. For heart failure, Bacillales (OR=0.955) and Anaerostipes (OR=0.899) were protective factors, while Ruminococcus UCG009 (OR=1.107), Eubacterium oxidoreducens group (OR=1.117), Selenomonadales (OR=1.106), Negativicutes (OR=1.107), Eubacterium eligens group (OR=1.139), and Flavonifractor (OR=1.144) were risk factors. Cochran's Q test showed no heterogeneity among SNPs of gut microbiota causally associated with CVDs (all P>0.05). The pleiotropy test found no evidence of horizontal pleiotropy (all P>0.05). Leave-one-out sensitivity analysis confirmed the robustness of the results. The MR Steiger directionality test supported the causal direction from gut microbiota (exposure) to CVDs (outcome). Conclusion ·Some gut microbiota have significant causal effects on CVDs; altering their abundance may influence CVD risk, providing potential targets for microbiota-based intervention strategies.

Key words： gut microbiota; cardiovascular disease; Mendelian randomization; genome-wide association study (GWAS); single-nucleotide polymorphism (SNP)

Cite this article

MA Huihua , YAN Kuipo , LIU Gang , XU Yazhou , ZHANG Lei , SUN Yanqin . Causal relationship between gut microbiota and cardiovascular diseases: a bidirectional Mendelian randomization analysis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(12) : 1606 -1619 . DOI: 10.3969/j.issn.1674-8115.2025.12.006

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