Akkermansia muciniphila, a member of the human intestinal microflora, is a potential next-generation probiotic. Therefore, the optimization of in vitroculture conditions for A. muciniphilais a promising research direction. In this study, an in vitrofermentation culture of A. muciniphilawas implemented using a novel bionic large intestine dynamic digestion model. Compared with static culture, the new bionic large intestine dynamic digestion model achieved 55.37% more biomass, accompanied by the significant growth of metabolites, such as acetic acid, propionic acid, and butyric acid. Moreover, the effects of fructo-oligosaccharide (FOS), blackberry concentrate powder, and metformin on the growth of A. muciniphilawere compared. FOS, blackberry concentrate powder, and metformin did not significantly affect biomass growth, but FOS increased butyric acid generation by A. muciniphilaby 32%. The outer membrane protein concentrations of A. muciniphilain FOS, polyphenols, and metformin are 30%–37% higher than that in the no added media. Electron microscopy indicated that the strains of the dynamic culture were superior to those of the static culture in terms of diameter and length. This study provides important progress in the industrial application of A. muciniphilaas a probiotic.