Precocious Puberty and Gut Microbiome: A Meta-analysis and Obesity Evaluation on the Taiwan Puberty Longitudinal Study

Precocious puberty (PP), particularly central precocious puberty (CPP), is a condition characterized by the early activation of the hypothalamic-pituitary-gonadal (HPG) axis. Emerging research suggests a role for the gut microbiome (GM) in pubertal regulation, with potential interactions between microbial metabolites, metabolic pathways, and endocrine signaling. Additionally, obesity is a known risk factor for early puberty, and its effects on gut microbial composition may further contribute to the progression of CPP. This study aims to investigate the relationship between gut microbiota, obesity, and puberty timing through a systematic review and meta-analysis, as well as an analysis of data from the Taiwan Puberty Longitudinal Study (TPLS).

A meta-analysis was conducted to identify microbial patterns associated with CPP, integrating findings from human and animal studies. The results revealed distinct microbial signatures in individuals with CPP, including increased abundances of Holdemania, Roseburia, Alistipes, Dialister, Enterococcus, Ruminococcus, Bilophila, and Lachnoclostridium, alongside reductions in Bacteroides, Anaerostipes, Megamonas, and Gemella. Additionally, gut microbiota-derived short-chain fatty acids (SCFAs), particularly butyric and propionic acid, were significantly reduced in CPP groups, suggesting a potential metabolic influence on pubertal onset.

In the TPLS cohort, comparisons between Control, Non-obese CPP, and Obese CPP groups revealed significant microbial and metabolic differences. Linear discriminant analysis (LEfSe) identified Prevotella as predominant in the Control group, while Acidaminococcus, Citrobacter, and Clostridia UCG-014 were enriched in the Non-obese CPP group. The Obese CPP group was characterized by an increased presence of CAG-56. Co-occurrence network analysis reveals the most connected microbial community in the Control group and the sparsest in the Obese CPP group. No significant differences in SCFAs levels were observed between the groups. Notably, Prevotella showed a significant negative correlation with bone age advancement, suggesting its potential role as a protective microbial biomarker.

These findings highlight the complex interplay between gut microbiota, SCFA metabolism, and endocrine function in CPP. The results support the hypothesis that gut microbial alterations may contribute to the metabolic regulation of puberty, with obesity further modulating these effects. Future research should explore the causal mechanisms linking gut microbiota to pubertal development and assess the potential of microbiome-based interventions for CPP management.