Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (4): 72-82.doi: 10.6040/j.issn.1671-7554.0.2025.0279

• Clinical Medicine • Previous Articles    

Mendelian randomization analysis of the causal relationships between gut microbiota, blood metabolites, and obesity

ZHAO Wanxia1, ZHAN Qunzhang1, JIN Ting2, LIU Yuxin1, QU Chongzheng3, WU Jianchun4   

  1. 1. Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China;
    2. First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China;
    3. Department of Acupuncture and Tuina, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510378, Guangdong, China;
    4. Department of General Surgery, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510378, Guangdong, China
  • Published:2026-04-09

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Abstract: Objective To utilise the Mendelian randomisation method to investigate the causal relationships between gut microbiota, blood metabolites, and obesity. Methods The human gut microbiota genome-wide association study(GWAS)data were obtained from the MiBioGen consortium database and utilised as exposure factors. The obesity data were obtained from the MRC Integrative Epidemiology Unit openGWAS database(IEU OpenGWAS)as outcomes. The data on 1,400 blood metabolites were sourced from the National Human Genome Research Institute-European Bioinformatics Institute Genome-Wide Association Studies Catalog(NHGRI-EBI GWAS Catalog)as mediators. Five methods(random-effects inverse variance weighting, MR Egger regression, weighted median, weighted mode, and simple mode)were employed for two-step Mendelian randomisation(TSMR)and multivariable Mendelian randomisation(MVMR)to explore the causal relationships between gut microbiota, blood metabolites, and obesity. Sensitivity analyses were conducted to assess the robustness of the MR results. Results A total of seven gut microbiota taxa were identified as having a causal relationship with obesity, while obesity was found to cause changes in five gut microbiota taxa. In the TSMR analysis, the genus Eubacterium hallii group, genus Oscillibacter, genus Oxalobacter, and genus Sutterella were found to be causally associated with obesity. MVMR analysis indicated that the association between genus Oxalobacter and obesity may be facilitated by 5alpha-androstan-3alpha,17alpha-diol monosulfate levels, with a mediation proportion of 8.504%. The association between genus Sutterella and obesity was likely mediated by the ratio of cholic acid to adenosine 5'-monophosphate(AMP), with a mediation proportion of 12.135%. Conclusion Current MR studies provide evidence supporting a causal relationship between genus Oxalobacter, genus Sutterella and obesity and potentially mediating metabolites.

Key words: Gut Microbiota, Obesity, Mendelian randomization, Cause-effect, Genetic analysis

CLC Number: 

  • R574
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