Dynamic Cultivation of Akkermansia muciniphila in an Improved Gastrointestinal Reactor: Enhanced Growth and Metabolomic Profiling

Akkermansia muciniphila, a next-generation probiotic in the human intestinal mucus layer, exhibits significant health-promoting properties. However, traditional static culture systems fail to replicate the dynamic peristaltic environment of the gastrointestinal tract, limiting understanding of its metabolic characteristics. This study employed an improved gastrointestinal bioreactor simulating intestinal peristalsis to investigate A. muciniphila growth dynamics and metabolomic profiles under dynamic conditions. Dynamic cultivation significantly enhanced bacterial growth. Biomass reached 1.32 ± 0.03 g/L in bovine heart infusion (BHI) medium and 2.03 ± 0.05 g/L in BHI supplemented with 2.5 g/L porcine mucin. These values represent increases of 45.05% and 123.08% relative to static BHI cultures, respectively. Dynamic conditions markedly elevated short-chain fatty acid production (acetic, propionic, isobutyric, isovaleric acids). Untargeted metabolomics identified 1463 metabolites with 1294 showing significant differential expression. Dynamic cultivation substantially altered amino acid biosynthesis, fatty acid, purine, and pyrimidine metabolism. These findings advance the understanding of A. muciniphila physiology and provide insights into its metabolic characteristics under simulated intestinal conditions.