Editors' ChoiceHost-Microbe Interactions

Microbial metabolites shape lipid metabolism

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Science Signaling  14 Apr 2020:
Vol. 13, Issue 627, eabc1552
DOI: 10.1126/scisignal.abc1552

Two bacterial fermentation products influence lipid metabolism and secretion in the small intestine.

Dietary lipids absorbed by small intestinal epithelial cells (IECs) are either metabolized in the IECs themselves or processed and stored in lipid droplets (LDs) before being secreted into lymphatic vessels as chylomicrons, lipoprotein particles that distribute the lipids systemically (see Wen and Rawls). Gut microbes affect the digestion, absorption, and secretion of dietary lipids. Araújo et al. found that live Lactobacillus paracasei or Escherichia coli or conditioned medium (CM) from these species reduced the secretion of chylomicrons from m-ICcl2 cells, a cell line derived from the mouse small intestine. A bacterial genetic screen and mass spectrometry analysis led to the identification of two end-products of bacterial carbohydrate fermentation that were necessary and sufficient to reproduce the effects of live bacteria or CM in m-ICcl2 cells: L. paracasei–produced L-lactate and E. coli–produced acetate. Both in vitro and in vivo, L. paracasei or L-lactate increased lipid storage in enterocytes, whereas E. coli or acetate decreased lipid storage and increased lipid consumption. L. paracasei or L-lactate also reduced circulating triglycerides in vivo. In m-ICcl2 cells, L-lactate was converted into malonyl-CoA, which inhibits lipid oxidation. In contrast, m-ICcl2 cells converted acetate to acetyl-CoA and adenosine monophosphate (AMP) and showed an increase in the activation of AMP kinase (AMPK) and in the abundance of the AMPK targets peroxisome proliferator–activated receptor–α (PPAR-α) and PPAR-γ coactivator 1α (PGC-1α), both of which are transcription factors that promote the expression of genes necessary for lipid oxidation. These findings identify a molecular mechanism by which microbial carbohydrate metabolism influences lipid metabolism and secretion in the gut.

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