Abstract
Despite the recognized capacity of the gut microbiota to regulate intestinal lipid metabolism, the role of specific commensal species remains undefined. Here, we aimed to understand the bacterial effectors and molecular mechanisms by which Lactobacillus paracasei and Escherichia coli regulate lipid metabolism in enterocytes. We show that L-lactate produced by L. paracasei inhibits chylomicron secretion from enterocytes and promotes lipid storage by a mechanism involving L-lactate absorption by enterocytes, its conversion to malonyl-CoA, and the subsequent inhibition of lipid beta-oxidation. In contrast, acetate produced by E. coli also inhibits chylomicron secretion by enterocytes but promotes lipid oxidation by a mechanism involving acetate absorption by enterocytes, its metabolism to acetyl-CoA and AMP, and the subsequent upregulation of the AMPK/PGC-1α/PPARα pathway. Our study opens perspectives for developing specific bacteria- and metabolite-based therapeutic interventions against obesity, atherosclerosis, and malnutrition by targeting lipid metabolism in enterocytes.