Transcriptomics and metabolomics reveal the adaption of Akkermansia muciniphila to high mucin by regulating energy homeostasis.

In gut, Akkermansia muciniphila (A. muciniphila) probably exerts its probiotic activities by the positive modulation of mucus thickness and gut barrier integrity. However, the potential mechanisms between A. muciniphila and mucin balance have not been fully elucidated. In this study, we cultured the bacterium in a BHI medium containing 0% to 0.5% mucin, and transcriptome and gas chromatography mass spectrometry (GC-MS) analyses were performed. We found that 0.5% (m/v) mucin in a BHI medium induced 1191 microbial genes to be differentially expressed, and 49 metabolites to be changed. The metabolites of sorbose, mannose, 2,7-anhydro-β-sedoheptulose, fructose, phenylalanine, threonine, lysine, ornithine, asparagine, alanine and glutamic acid were decreased by 0.5% mucin, while the metabolites of leucine, valine and N-acetylneuraminic acid were increased. The association analysis between transcriptome and metabolome revealed that A. muciniphila gave strong responses to energy metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways to adapt to high mucin in the medium. This finding showed that only when mucin reached a certain concentration in a BHI medium, A. muciniphila could respond to the culture environment significantly at the level of genes and metabolites, and changed its metabolic characteristics by altering the effect on carbohydrates and amino acids.