Gut microbiota phospholipids regulate intestinal gene expression and can counteract the effects of antibiotic treatment.

ABSTRACT: Early-life antibiotic exposure perturbs the developing gut microbiome and increases risk for immune disorders such as type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. Comparing germ-free and conventional mice, we identified 747 intestinal lipid compounds and defined a subset of gut microbially-produced lipids (GMPLs). Antibiotic treatment disrupted GMPL profiles in mice and in human volunteers, with partial restoration in mice after cecal microbiota transplantation. Among affected compounds, four phospholipids: LPG(13:0), LPG(16:0), LPG(18:0), and PG(15:0_15:0), were structurally defined and tested functionally. These lipids suppressed LPS-induced NFkB activation, modulated innate immune gene expression in intestinal epithelial cells, and enhanced epithelial cell mitochondrial respi

SUBMITTER: Blaser M 

PROVIDER: S-EPMC12687810 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature