Precocious puberty and gut microbiome: a systematic review and meta-analysis

Central precocious puberty (CPP) is a condition that affects prepubertal children, particularly girls. Recent evidence suggests an association between the gut microbiome (GM) and CPP. This study aims to explore this association. We analyzed data from studies investigating the association between GM and CPP. Various databases were searched for relevant articles published from database inception to December 31, 2023. Standardized mean difference values were calculated and depicted in forest plots. Furthermore, subgroup analyses by type of study subject (animals vs. humans) were performed. The final analysis included 9 studies. Five were human studies, whereas the remaining four were animal (rats or mice) studies. In the precocious puberty group, the abundances (at the genus level) of Holdemania, Roseburia, Alistipes, Dialister, Enterococcus, Ruminococcus, Bilophila, and Lachnoclostridium increased significantly, whereas those of Bacteroides, Anaerostipes, Megamonas, and Gemella decreased significantly. Furthermore, for this group, the Shannon index for alpha diversity was increased in human studies and decreased in animal studies compared to the control group. Notably, the levels of major short-chain fatty acids, butyric and propionic acids, were significantly reduced in the precocious puberty group. There was an association between CPP and GM. Both subgroups revealed that microbiome profiles vary across individuals with precocious puberty. IMPACT: To our knowledge, this is the first systematic review and meta-analysis to explore the association between the gut microbiome and precocious puberty in both human and animal models. Our findings reveal distinct microbial patterns in individuals with CPP, including consistent alterations in 12 bacterial genera and significant changes in short-chain fatty acid levels. By identifying reproducible microbial signatures and metabolites associated with CPP, this study lays the groundwork for microbiome-targeted interventions alongside traditional hormonal therapies. The study addresses key methodological inconsistencies in existing literature, highlighting the need for standardized protocols in future research on the gut-puberty axis.