AUTHOR=Xu Yating , Ning Li , Si Yu , Li Xiu , Wang Ruyue , Ren Qingling 

TITLE=Metformin-mediated intestinal AMPK activation ameliorates PCOS through gut microbiota modulation and metabolic pathways

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1526109

DOI=10.3389/fendo.2025.1526109

ISSN=1664-2392

ABSTRACT=IntroductionPolycystic ovary syndrome (PCOS) is a complex disorder characterized by metabolic and ovulatory dysfunctions, often associated with an imbalance in gut microbiota. Despite current treatments, effective management strategies targeting underlying mechanisms remain limited.MethodsIn this study, we used a rat model of PCOS induced by letrozole and a high-fat diet. The effect of intestinal AMP-activated protein kinase (AMPK) activation was evaluated through metformin administration, the most commonly used AMPK activator. We analyzed metabolic parameters, ovulatory functions, gut microbiota composition, and serum levels of Indole-3-carboxaldehyde (I3A), a metabolite involved in inflammation and apoptosis regulation.ResultsMetformin treatment significantly reversed metabolic disorders and restored ovulatory functions in PCOS rats. Moreover, metformin treatment led to notable improvements in gut microbiota composition and an increase in serum I3A levels, which have been shown to mitigate inflammation and apoptosis.DiscussionThis study highlights the therapeutic potential of targeting intestinal AMPK in managing PCOS.  By improving both metabolic and reproductive health, activation of AMPK may offer a promising approach for restoring physiological balance in PCOS patients.