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Updated: Jul 3, 2025
Murine Fecal Isolation and Microbiota Transplantation
Published on: May 26, 2023
Causal relationship between gut microbiome and sex hormone-binding globulin: A bidirectional two-sample Mendelian
Ziqiao Yan1, Zheng Zheng2, Tiantian Xia3
1Department of Traditional Chinese Medicine, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Problem:
Currently, 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 Study:
Bidirectional 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.
Results:
When we set gut microbiome as exposure and SHBG as outcome, we identified nine causal relationships. In males, Coprobacter (PIVW = 2.01 × 10-6 ), Ruminococcus2 (PIVW = 3.40 × 10-5 ), Barnesiella (PIVW = 2.79 × 10-2 ), Actinobacteria (PIVW = 3.25 × 10-2 ) and Eubacterium fissicatena groups (PIVW = 3.64 × 10-2 ) were associated with lower SHBG levels; Alphaproteobacteria (PIVW = 1.61 × 10-2 ) is associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 9.75 × 10-3 ) and Defluviitaleaceae UCG011 (PIVW = 3.67 × 10-2 ) were associated with higher SHBG levels; Victivallaceae (PIVW = 2.23 × 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 × 10-2 ) and Clostridiales (PIVW = 4.36 × 10-2 ) were associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 7.44 × 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.
Conclusions:
This 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.
