Association between sex hormone levels and gut microbiota composition and diversity – A Systematic Review Original paper

What was reviewed?

This systematic review examined the association between sex hormone levels, primarily estrogen and testosterone, and the composition and diversity of the human gut microbiota. The review synthesized findings from 13 observational human studies that employed next-generation sequencing techniques to assess how fluctuations or differences in sex hormones correlate with specific bacterial taxa and microbial diversity indices. The focus was on healthy individuals as well as those with conditions characterized by altered hormone profiles, such as polycystic ovary syndrome (PCOS) and postmenopausal status.

Who was reviewed?

The review encompassed a total of 812 participants from diverse geographic locations including the USA, China, Poland, South Korea, and Spain. The vast majority of participants were women (91%), with men representing only 9%. The average age across studies was 41 years. Included studies ranged from cross-sectional to case-control designs and involved healthy adults, postmenopausal women, and women with hormone-related conditions such as PCOS and breast cancer. Studies varied in methods of hormone measurement, microbiota sequencing regions, and diversity metrics, reflecting heterogeneity in approaches.

Most important findings

The review found consistent associations between estrogen levels and gut microbial composition and alpha diversity. Higher estrogen was linked to increased abundance of Bacteroidetes and decreased Firmicutes, especially within the Ruminococcaceae family, and a lower Firmicutes:Bacteroidetes ratio, often associated with better gut health. Estrogen positively correlated with genera such as Ruminococcus and inversely with Bacteroides and some Firmicutes genera. In postmenopausal women, estrogen correlated strongly with increased alpha diversity metrics. Testosterone showed positive correlations with genera like Ruminococcus and Acinetobacter in men, while in women with PCOS, altered testosterone levels correlated with increased abundance of Escherichia/Shigella and other taxa. Testosterone was also associated with shifts in alpha diversity, though findings were less consistent than for estrogen. These hormone-microbiota relationships may be mediated by microbial enzymatic activities, such as β-glucuronidase production, which modulates hormone enterohepatic circulation.

Key implications

This review highlights a significant, yet complex, bidirectional interaction between sex hormones and gut microbiota composition and diversity. These interactions may contribute to sex-based differences in disease pathogenesis, particularly in hormone-sensitive conditions like PCOS, breast cancer, osteoporosis, and gastrointestinal disorders. The findings suggest that modulation of the microbiota could represent a novel therapeutic avenue to influence systemic hormone levels and related disease outcomes. However, heterogeneity in study design and population underscores the need for more standardized, longitudinal studies, including male participants, to unravel mechanistic pathways and causal relationships. Ultimately, understanding the sex hormone–microbiota axis may facilitate personalized interventions targeting microbial profiles to optimize hormone-related health.