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

Area of Science:

• Human Genetics
• Microbiology
• Endocrinology

Background:

• The gut microbiota is increasingly linked to sex hormone regulation.
• The precise causal relationship between sex hormone-binding globulin (SHBG) and the gut microbiome remains unclear.

Purpose of the Study:

• To investigate the bidirectional causal effects between SHBG and the gut microbiome using Mendelian randomization.

Main Methods:

• Employed bidirectional two-sample Mendelian randomization (MR) analysis.
• Utilized genome-wide association study (GWAS) summary statistics for gut microbiome and SHBG.
• Applied multiple MR methods including Inverse-Variance Weighting (IVW) and weighted median, with sensitivity analyses for reliability.

Main Results:

• Identified nine causal relationships with gut microbiome as exposure and SHBG as outcome, varying by sex.
• In males, specific bacteria like Coprobacter and Ruminococcus2 were associated with lower SHBG, while Alphaproteobacteria was linked to higher SHBG.
• In females, Lachnoclostridium and Defluviitaleaceae UCG011 were linked to higher SHBG, and Victivallaceae to lower SHBG.
• Reverse MR analysis showed SHBG causally affects gut microbiota, with Dorea and Clostridiales associated with higher SHBG in males, and Lachnoclostridium in females.
• No significant heterogeneity or pleiotropy was detected.

Conclusions:

• Establishes a potential bidirectional causal relationship between the gut microbiome and SHBG levels.
• Suggests novel therapeutic and preventive strategies for conditions related to abnormal sex hormone levels.