Adjunctive Akkermansia muciniphila postbiotic supplementation modulates metabolic and endocrine profiles in obesity-associated polyendocrine metabolic ovarian syndrome: A randomized controlled trial.

BACKGROUND & AIMS: As a flagship next-generation probiotic, Akkermansia muciniphila (AKK) has been extensively validated for its prominent therapeutic advantages against metabolic diseases. However, clinical research on AKK remains scarce owing to its exclusion from the Official Catalog of Approved Food Microbial Strains in China. METHODS: In this study, 100 women with obesity-associated polyendocrine metabolic ovarian syndrome (PMOS) receiving standardized oral contraceptive therapy were randomized to receive AKK postbiotic supplementation or placebo, and the adjunctive effects of AKK postbiotics were evaluated on body weight, hyperandrogenic manifestations, glucose-lipid metabolism, and gut microbiota composition. RESULTS: The results showed that AKK postbiotic intervention achieved a significantly greater reduction in weight than placebo (1.92 vs. 0.37 kg, p < 0.001), relieved hyperandrogenic manifestations including hirsutism and acne. Additionally, AKK postbiotics markedly improved glucose-insulin homeostasis and dyslipidemia, with significantly greater reductions from baseline observed in serum LH levels (3.67 vs. 1.98 mIU/mL, p < 0.05), LH/FSH ratio (0.70 vs. 0.37, p < 0.05), and testosterone concentrations (7.74 vs. 4.97 ng/dL, p < 0.05) compared with placebo. Furthermore, AKK postbiotics were associated with favorable post-intervention microbial characteristics, including increased microbial diversity and altered abundance patterns of specific taxa, such as enrichment of Bifidobacterium and Faecalibacterium and decreased abundance of Bacteroides and Fusobacterium. CONCLUSION: Taken together, this study provides the first clinical evidence that adjunctive AKK postbiotic supplementation combined with standard oral contraceptive therapy may further improve metabolic and endocrine abnormalities in women with obesity-associated PMOS, thus establishing a promising therapeutic strategy for PMOS and laying a robust foundation for the future clinical translation of AKK. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2400090949).