Amuc_1100 Reproduces Protective Effects of Live and Pasteurized Akkermansia muciniphila Against Metabolic and Reproductive Dysfunction in PCOS Mice

Akkermansia muciniphila (AKK) and its pasteurized form (pAKK) have demonstrated metabolic benefits, but whether their outer membrane protein Amuc_1100 can reproduce these effects in polycystic ovary syndrome (PCOS) remains unclear. We compared live AKK, pAKK, and Amuc_1100 in a mouse model of PCOS induced by dehydroepiandrosterone (DHEA) and a high-fat diet (HFD), with oral interventions initiated concurrently with model induction. Amuc_1100 reproduced several protective effects of live AKK and pAKK, improving glucose tolerance, insulin responsiveness, lipid profiles, estrous cyclicity, androgen levels, and ovarian morphology. These improvements were accompanied by reduced periovarian adipocyte hypertrophy, changes in brown adipose tissue-associated gene expression, and improved colonic morphology and tight junction-associated markers. Circulating lipopolysaccharide-binding protein, interleukin-1β, and interleukin-18 levels were also lower following intervention. Ovarian transcriptomic analysis revealed changes in inflammation-related pathways after Amuc_1100 administration, accompanied by reduced ovarian Il1b and Il18 expression and attenuation of NF-κB/NLRP3/GSDMD-associated inflammatory and pyroptosis-related signaling. Together, these findings suggest that Amuc_1100 attenuates the development of metabolic and reproductive abnormalities in a DHEA+HFD-induced PCOS mouse model. Further studies are required to establish the underlying mechanisms and determine its relevance to human PCOS.