Effects of modified-BHI medium on the growth and metabolites of Akkermansia muciniphila

Akkermansia muciniphila ( Akk ) has recently become popular due to its therapeutic effect on various diseases. However, Akk ’s high-density cultivation is difficult due to its anaerobic characteristics. Therefore, Akk was cultured with modified brain–heart infusion (M-BHI) to reach 10 11 CFU/mL. 1 H-NMR determined the metabolites of Akk and validated them by an amino acid analyzer. Compared to the BHI, Akk significantly up-regulated lactate, histidine, fumaric acid, cytidine, threonine, arginine, and hydroxyproline in the M-BHI and significantly down-regulated methionine, trimethylamine, and sarcosine. Regarding pathway enrichment analysis, histidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism mainly regulate differential metabolites. In addition, M-BHI alters the metabolic profile by affecting Akk ’s involvement in amino acid metabolism remodeling. Changed metabolites showed that Akk fermentation in M-BHI may play a physiological role in regulating immune homeostasis and reducing risk factors related to diseases. Therefore, M-BHI provides a promising reference for Akk cultivation in future industrial preparation.