Limosilactobacillus reuteri ameliorates diet-associated metabolic dysfunction in PCOS-like rats: associations with intestinal lipid remodeling and GPR120-related regulation

Background Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder frequently accompanied by dyslipidemia. However, the relationships among Limosilactobacillus reuteri ( L. reuteri ) supplementation, gut microbiota-associated lipid remodeling, and PCOS-related metabolic dysfunction remain unclear. Methods A high-fat diet combined with dehydroepiandrosterone-induced PCOS-like rat model (HFHA) was established to evaluate the effects of L. reuteri supplementation. Gut microbiota composition, lipidomic profiles, jejunal GPR120/PPARγ-related molecular markers, and fatty-acid transporter expression were assessed. Potential GPR120-associated involvement was pharmacologically evaluated using AH-7614, with complementary experiments performed in Caco-2 cells. Results L. reuteri alleviated high-fat diet-associated metabolic dysfunction, reducing body-weight gain, dyslipidemia, and hepatic steatosis. Formal interaction analyses further supported metabolic-context-dependent effects for several metabolic and endocrine endpoints. L. reuteri supplementation altered gut microbial composition and was associated with increased abundances of colonic fatty-acid features putatively annotated as FA(22:5), FA(24:5), and FA(24:6). These colonic lipid-profile changes occurred alongside increased jejunal GPR120 expression, reduced PPARγ abundance, and lower CD36/FABP2 expression. AH-7614 co-treatment attenuated several metabolic, reproductive, and intestinal effects associated with L. reuteri supplementation. In Caco-2 cells, pharmacological modulation or overexpression of GPR120 reduced FFA-induced CD36 and FABP2 expression and intracellular lipid accumulation, whereas AH-7614 or Barbadin treatment attenuated these responses. Conclusion L. reuteri improves diet-associated metabolic dysfunction in PCOS-like rats, accompanied by gut microbiota remodeling, altered intestinal lipid profiles, reduced intestinal lipid accumulation, and GPR120-associated regulation of CD36 and FABP2. These findings support a potential role for altered intestinal lipid handling in the metabolic effects of L. reuteri , although the identities, origins, and direct receptor activities of the relevant lipid mediators require further investigation.