The causal impact of gut microbiota on circulating adipokine concentrations: a two-sample Mendelian randomization study

Evidence from previous experimental and observational research demonstrates that the gut microbiota is related to circulating adipokine concentrations. Nevertheless, the debate as to whether gut microbiome composition causally influences circulating adipokine concentrations remains unresolved. This study aimed to take an essential step in elucidating this issue. We used two-sample Mendelian randomization (MR) to causally analyze genetic variation statistics for gut microbiota and four adipokines (including adiponectin, leptin, soluble leptin receptor [sOB-R], and plasminogen activator inhibitor-1 [PAI-1]) from large-scale genome-wide association studies (GWAS) datasets. A range of sensitivity analyses was also conducted to assess the stability and reliability of the results. The composite results of the MR and sensitivity analyses revealed 22 significant causal associations. In particular, there is a suggestive causality between the family Clostridiaceae1 (IVW: β = 0.063, P = 0.034), the genus Butyrivibrio (IVW: β = 0.029, P = 0.031), and the family Alcaligenaceae (IVW: β=-0.070, P = 0.014) and adiponectin. Stronger causal effects with leptin were found for the genus Enterorhabdus (IVW: β=-0.073, P = 0.038) and the genus Lachnospiraceae (NK4A136 group) (IVW: β=-0.076, P = 0.01). Eight candidate bacterial groups were found to be associated with sOB-R, with the phylum Firmicutes (IVW: β = 0.235, P = 0.03) and the order Clostridiales (IVW: β = 0.267, P = 0.028) being of more interest. In addition, the genus Roseburia (IVW: β = 0.953, P = 0.022) and the order Lactobacillales (IVW: β=-0.806, P = 0.042) were suggestive of an association with PAI-1. This study reveals a causal relationship between the gut microbiota and circulating adipokines and may help to offer novel insights into the prevention of abnormal concentrations of circulating adipokines and obesity-related diseases.