A lysate of a multi-strain probiotic formulation inhibits cell growth and oxidative phosphorylation in colorectal cancer cells via a ceramide-mediated mechanism.

The multi-strain probiotic formulation (MPF - Oxxyslab™) regulates several biological processes, including oxygenation in human and mouse models of neurodegenerative diseases. Its effect on oxidative metabolism of tumour cells has not yet been investigated. Employing a polarographic approach, we examined the effect of a lysate of MPF and its constituent strains on oxidative phosphorylation (OXPHOS) in colorectal cancer cells. Results indicate that MPF lysate selectively inhibits OXPHOS in undifferentiated but not in differentiated Caco-2 cells. Ceramides, produced through bacterial sphingomyelinase activity, mediate the inhibitory effects of MPF lysate, and the efficacy of the lysate of individual MPF strains in blocking cellular respiration varies due to strain-specific differences in ceramide production. Our results demonstrate that MPF lysate exhibits anti-OXPHOS activity in human colorectal carcinoma cells, selectively targeting undifferentiated Caco-2 cells but not differentiated ones. The reliance of colorectal cancer cells on OXPHOS provides a scientific basis for exploring MPF probiotic formulation as a complementary approach to conventional pharmacology.