An early-life microbiota metabolite protects against obesity by regulating intestinal lipid metabolism

Cell Host Microbe. 2023 Oct 11;31(10):1604-1619.e10. doi: 10.1016/j.chom.2023.09.002. Epub 2023 Oct 3.


The mechanisms by which the early-life microbiota protects against environmental factors that promote childhood obesity remain largely unknown. Using a mouse model in which young mice are simultaneously exposed to antibiotics and a high-fat (HF) diet, we show that Lactobacillus species, predominant members of the small intestine (SI) microbiota, regulate intestinal epithelial cells (IECs) to limit diet-induced obesity during early life. A Lactobacillus-derived metabolite, phenyllactic acid (PLA), protects against metabolic dysfunction caused by early-life exposure to antibiotics and a HF diet by increasing the abundance of peroxisome proliferator-activated receptor γ (PPAR-γ) in SI IECs. Therefore, PLA is a microbiota-derived metabolite that activates protective pathways in the small intestinal epithelium to regulate intestinal lipid metabolism and prevent antibiotic-associated obesity during early life.

Keywords: Lactobacillus; antibiotics; arachnoid barrier; brain fibroblasts; early-life; intestinal epithelium; leptomeninges; metabolism; microbiota; obesity; single-cell RNA sequencing; tricellular junction.

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Child
  • Diet, High-Fat / adverse effects
  • Humans
  • Lipid Metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microbiota*
  • Pediatric Obesity*
  • Polyesters


  • Anti-Bacterial Agents
  • Polyesters