The Childhood Estrobolome: A Missing Link in Early Puberty Onset.

Abstract

Precocious puberty, defined as the onset of secondary sexual characteristics before age 8 in girls, is rising globally with most cases lacking a clearly identifiable cause. The biome is increasingly recognized as a regulator of hormonal homeostasis, yet its role in childhood hormonal programming remains largely unexplored. The estrobolome - the collection of gut bacteria encoding β-glucuronidase (β-GUS) enzymes - controls enterohepatic estrogen recycling in adult women but has never been systematically characterized in prepubertal girls. This narrative review proposes and synthesizes evidence supporting the hypothesis that early-life dysregulation of the childhood estrobolome may prime the hypothalamic-pituitary-gonadal (HPG) axis for premature activation, contributing to early puberty onset in girls. Elevated fecal β-GUS activity has been documented in girls with central precocious puberty (CPP), consistent with altered estrobolome activity during pubertal development. Early-life exposures - including antibiotics, high-fat diet, cesarean delivery, formula feeding, and endocrine-disrupting chemicals - modulate the childhood microbiome in ways that enrich β-GUS-producing taxa. The resulting increase in enterohepatic estrogen reabsorption may provide a chronic low-level estrogenic signal sufficient to sensitize kisspeptin neurons and initiate premature GnRH pulsatility. Overall, the childhood estrobolome represents a compelling but entirely uncharacterized mechanistic bridge between gut dysbiosis and early puberty. Direct characterization of β-GUS activity in healthy prepubertal girls and longitudinal cohort studies are urgently needed. Microbiome-targeted interventions including probiotics, dietary modification, and antibiotic stewardship may hold promise as preventive strategies.