Comparative cytotoxicity and molecular profiling of Akkermansia muciniphila postbiotics in AGS and HCT116 cells

The gut microbiota supports epithelial integrity and overall health, with Akkermansia muciniphila receiving particular attention. Postbiotics are defined as preparations composed of inactivated bacterial cells and/or their components, offering stability that makes them attractive for food applications. In this study, we compared postbiotics derived from three different Akkermansia muciniphila strains in gastric (AGS) and colorectal (HCT116) cancer cell lines. Cell metabolic activity (MTT assay) was measured over 24–72 h, and molecular composition was profiled using LC-QTOF-MS and 1 H-NMR. All preparations reduced MTT signal relative to controls in a dose- and time-dependent manner, showing broadly similar magnitudes with strain-specific trends. Proteomic and metabolomic analyses identified proteins and metabolites, six of which were linked to epithelial and redox pathways relevant to gastrointestinal biology. This study provides a direct, strain-to-strain comparison integrating cytotoxic screening with proteomic and 1 H-NMR metabolomic profiling of Akkermansia muciniphila postbiotics. • Comparative cytotoxicity of three Akkermansia muciniphila postbiotics was evaluated. • Cell viability was reduced dose- and time-dependently in AGS and HCT116 cells. • LC-QTOF-MS and 1 H-NMR revealed bioactivity–metabolite profile associations. • Metabolites linked to redox balance and epithelial function were identified.