The role of sex steroids in the human gut microbiome

Sex steroid hormones and the gut microbiome are increasingly recognized as bidirectionally interacting regulators of growth, metabolism, and endocrine maturation. While most research has focused on adults, accumulating evidence indicates that these interactions are established early in life and influence pubertal timing, metabolic homeostasis, and neuroendocrine development. This review synthesizes current human evidence on microbiome-sex steroid relationships across childhood and adolescence, highlighting mechanistic insights and clinical implications for pediatric endocrinology.

Gut microbes modulate steroid hormone metabolism through enzymatic deconjugation and enterohepatic circulation, while pubertal hormonal shifts reciprocally influence microbial diversity and function. Early-life dysbiosis linked to antibiotics, diet, or obesity may alter hypothalamic-pituitary-gonadal activity. Microbial metabolites such as short-chain fatty acids, bile acids, and tryptophan derivatives regulate immune, metabolic, and neuroendocrine pathways, affecting growth and insulin sensitivity. Disruptions of this microbiome-hormone axis are implicated in pubertal timing disorders, metabolic dysfunction, polycystic ovary syndrome (PCOS), and inflammatory intestinal diseases, whereas fiber-rich diets and probiotics may help restore balance.

The microbiome-sex steroid axis constitutes a fundamental component of pediatric endocrine development. Understanding this bidirectional relationship provides a framework for microbiome-informed strategies aimed at preventing and managing pubertal, metabolic, and neuroendocrine disorders during childhood and adolescence.