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

作者：Catherine D. Shelton, E. L. Sing, Jessica Mo, Nicolas G. Shealy, Woongjae Yoo, Julia Thomas, Gillian Nicole Fitz, Pollyana Ribeiro Castro, Tara T. Hickman, Teresa P. Torres, Nora J. Foegeding, Jacob K. Zieba, M. Wade Calcutt, Simona G. Codreanu, Stacy D. Sherrod, JOHN A. JUN. MCLEAN, Sun H. Peck, Fan Yang, Nicholas O. Markham, Min Liu, Mariana Xavier Byndloss · 发表于：Cell Host & Microbe · 年份：2023 · DOI：10.1016/j.chom.2023.09.002 · 被引用次数：123 · 研究领域：Gut microbiota and health、Diet and metabolism studies、Gastrointestinal motility and disorders

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.