Causal relationship between gut microbiome and sex hormone-binding globulin: A bidirectional two-sample Mendelian randomization study

ProblemCurrently, there is a variety of evidence linking the gut microbiota to changes in sex hormones. In contrast, the causal relationship between SHBG, a carrier of sex hormones, and the gut microbiota is unclear.Method of StudyBidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between SHBG and the gut microbiome. Summary statistics of genome-wide association studies (GWASs) for the gut microbiome and SHBG were obtained from public datasets. Inverse-variance weighting (IVW), weighted median, weighted mode, MR-Egger and simple mode methods were used to operate the MR analysis. F-statistics and sensitivity analyses performed to evaluate bias and reliability.ResultsWhen we set gut microbiome as exposure and SHBG as outcome, we identified nine causal relationships. In males, Coprobacter (PIVW = 2.01 x 10-6), Ruminococcus2 (PIVW = 3.40 x 10-5), Barnesiella (PIVW = 2.79 x 10-2), Actinobacteria (PIVW = 3.25 x 10-2) and Eubacterium fissicatena groups (PIVW = 3.64 x 10-2) were associated with lower SHBG levels; Alphaproteobacteria (PIVW = 1.61 x 10-2) is associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 9.75 x 10-3) and Defluviitaleaceae UCG011 (PIVW = 3.67 x 10-2) were associated with higher SHBG levels; Victivallaceae (PIVW = 2.23 x 10-2) was associated with lower SHBG levels. According to the results of reverse MR analysis, three significant causal effect of SHBG was found on gut microbiota. In males, Dorea (PIVW = 4.17 x 10-2) and Clostridiales (PIVW = 4.36 x 10-2) were associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 7.44 x 10-4) was associated with higherr SHBG levels. No signifcant heterogeneity of instrumental variables or horizontal pleiotropy was found in bidirectional two-sample MR analysis.ConclusionsThis study may provide new insights into the causal relationship between the gut microbiome and sex hormone-binding protein levels, as well as new treatment and prevention strategies for diseases such as abnormal changes in sex hormones.