Fermentation Products of Commensal Bacteria Alter Enterocyte Lipid Metabolism

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. [Display omitted] •Fermentation products secreted by gut commensals regulate enterocyte lipid metabolism•L-lactate secreted by L. paracasei promotes lipid storage by generating malonyl-CoA•Acetate secreted by E. coli promotes lipid oxidation via AMPK/PGC-1α/PPARα pathway Araújo et al. demonstrate that L-lactate and acetate produced by commensal bacteria differentially program enterocyte metabolism and secretion of absorbed dietary lipids. L. paracasei-produced L-lactate induces enterocytes to store lipids through its conversion to malonyl-CoA, while E. coli-produced acetate induces enterocytes to oxidize lipids by upregulating the AMPK/PGC-1α/PPARα pathway.