Dietary modulation of pubertal timing: gut microbiota-derived SCFAs and neurotransmitters orchestrate hypothalamic maturation via the gut-brain axis.

BACKGROUND

The global rise in early pubertal activation is closely linked to dietary patterns and gut microbiota (GM) dysbiosis. This review synthesizes evidence on how GM-derived metabolites modulate hypothalamic maturation and pubertal timing through the gut-brain axis.

METHODS

Following PRISMA guidelines, we conducted a systematic review of human and animal studies (PubMed, Medline, CNKI, Wanfang) up to October 2024, focusing on dietary impacts (high-fat/high-sugar) on GM composition and puberty onset. Inclusion criteria prioritized studies linking GM metabolites to HPGA activation.

RESULTS

High-fat/high-sugar diets reduce GM diversity and short-chain fatty acid (SCFA) production (e.g., butyrate, acetate), impair gut barrier integrity, and promote systemic inflammation. Dysbiosis in SCFA-producing taxa (Roseburia, Faecalibacterium) and neurotransmitter-modulating genera (Bifidobacterium, Lactobacillus) disrupts leptin/insulin signaling and kisspeptin-GnRH interactions, accelerating HPGA activation. Animal studies demonstrate SCFA supplementation delays puberty by reducing hypothalamic inflammation, while human data reveal ethnic and dietary variability in GM profiles. Western diets heighten altered pubertal timing risk via GM-mediated HPGA dysregulation, whereas fiber-rich Mediterranean diets exhibit protective effects.

CONCLUSION

GM dysbiosis and SCFA depletion are pivotal in diet-driven alterations of pubertal timing. Culturally adapted interventions targeting microbiota-metabolite interactions may mitigate risks of early puberty onset.