Lacticaseibacillus rhamnosus DACN152 effectively ameliorated letrozole-induced polycystic ovary syndrome: sex hormone homeostasis, microbiota and metabolite profiles

Abstract

This study investigated the potential role of Lacticaseibacillus rhamnosus DACN152 (DACN152) in ameliorating polycystic ovary syndrome (PCOS). Using a letrozole-induced PCOS murine model, we demonstrated that DACN152 attenuated ovarian histopathological damage, restored estrous cyclicity, and normalized sex hormone levels. Furthermore, DACN152 enhanced ovarian steroidogenesis by regulating key steroidogenic genes (StAR, CYP17A1, and CYP19A1) and sex hormone receptors (Lhr and Pgr), while concurrently suppressing ovarian apoptosis through modulation of apoptotic regulators (Bax and Bcl-2). These changes were corroborated at the protein level. Additionally, DACN152 significantly restructured the gut microbiota composition in PCOS mice, marked by reduced abundances of Bacteroidota, Verrucomicrobiota, Dubosiella, and Akkermansia, alongside increased abundances of Firmicutes, Campylobacterota, Allobaculum, Ruminococcus, and Blautia. Serum metabolomic analysis revealed elevated levels of bile acids, including chenodeoxycholic acid (CDCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), and cholic acid (CA). Collectively, these findings provide a theoretical basis for the development of probiotic-functional foods for PCOS.