Lobetyolin reshapes gut microbiota and bile acid metabolism to improve androgen-driven PCOS phenotypes in mice

作者：Lijuan Li, Pingping Lin, Pingping Lin, Yuning Zhang, Siqi Wang, Jingtao Liang, Ruyu Wang, Guofeng Duan, Aixiang Chen · 发表于：Frontiers in Microbiology · 年份：2026 · DOI：10.3389/fmicb.2026.1810261 · 研究领域：Ovarian function and disorders、Hypothalamic control of reproductive hormones、Reproductive System and Pregnancy

Aim To clarify the molecular mechanisms through which lobetyolin (LT) modifies the gut microbiota-bile acid axis to multitarget the regulation of hyperandrogenism, insulin resistance, chronic low-grade inflammation, and endometrial dysfunction, consequently breaking the vicious cycle and improving the pathological phenotype of polycystic ovary syndrome (PCOS), thereby establishing a theoretical basis and experimental validation for the advancement of LT as a systemic therapeutic agent for PCOS. Methods A DHEA-induced PCOS murine model was administered LT (i.p. for 28 days). We monitored hormone levels in the serum, glucose tolerance, and estrus cycle. Ovarian steroidogenic enzyme expression (CYP11A1, CYP17A1, and CYP19A1) was assessed by qPCR, while inflammatory markers (IL-6, TNF-α, TLR4, and NF-κB) were quantified by ELISA.16S rRNA sequencing was performed for gut microbiota and focused bile acid metabolomics. Uterine molecular markers were evaluated through vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor (VEGFR2), tissue inhibitor of metalloproteinases 1(TIMP1/2), and matrix metalloproteinase 2/9 (MMP2/9). Main results LT restored estrous cyclicity, lowered the LH/FSH ratio and serum testosterone levels, and improved insulin sensitivity. Androgen Network Modulation: LT decreased CYP11A1/CYP17A1 and elevated CYP19A1, showing “upstream inhibition-downstream activation.” LT also boosted α-diversity, adjusted the F/B ratio, enriched Dub...