Abstract: In this study, Akkermansia muciniphila (Akk) was cultured to a concentration of more than 109 CFU/mL in optimized liquid thioglycolate medium. Besides, the differential metabolites in the fermentation supernatants from the original and optimized medium were analyzed by non-targeted metabolomics, and the physiological functions of the characteristic products were evaluated. The results showed that when cultured in the optimized medium, Akk produced higher amounts of various functional metabolites such as propionic acid, bardoxifene, docetaxel and vinblastine by affecting protein digestion and absorption, aminoacyl tRNA biosynthesis, bile secretion, ATP-binding cassette (ABC) transporter, and the metabolic pathways of amino acid biosynthesis. These metabolites could be directly related to anti-cancer, anti-inflammatory, anti-obese and other functions. This study provides solid evidence that Akk can function as a probiotic agent and postbiotic to regulate many diseases, and lays a theoretical foundation for future industrial production.

Key words: Akkermansia muciniphila; medium optimization; differential metabolites; metabolic pathways; postbiotic