Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages

EMBO Rep. 2019 Apr;20(4):e46927. doi: 10.15252/embr.201846927. Epub 2019 Feb 19.


A lacteal is a blunt-ended, long, tube-like lymphatic vessel located in the center of each intestinal villus that provides a unique route for drainage of absorbed lipids from the small intestine. However, key regulators for maintaining lacteal integrity are poorly understood. Here, we explore whether and how the gut microbiota regulates lacteal integrity. Germ depletion by antibiotic treatment triggers lacteal regression during adulthood and delays lacteal maturation during the postnatal period. In accordance with compromised lipid absorption, the button-like junction between lymphatic endothelial cells, which is ultrastructurally open to permit free entry of dietary lipids into lacteals, is significantly reduced in lacteals of germ-depleted mice. Lacteal defects are also found in germ-free mice, but conventionalization of germ-free mice leads to normalization of lacteals. Mechanistically, VEGF-C secreted from villus macrophages upon MyD88-dependent recognition of microbes and their products is a main factor in lacteal integrity. Collectively, we conclude that the gut microbiota is a crucial regulator for lacteal integrity by endowing its unique microenvironment and regulating villus macrophages in small intestine.

Keywords: VEGF‐C; intestinal lymphatic vasculature; lacteal; macrophage; microbiota.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Biological Transport
  • Biomarkers
  • CX3C Chemokine Receptor 1 / metabolism
  • Fluorescent Antibody Technique
  • Gastrointestinal Microbiome*
  • Intestinal Absorption
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / ultrastructure
  • Lipid Metabolism
  • Macrophages / metabolism*
  • Mice
  • Microvessels / metabolism
  • Myeloid Differentiation Factor 88 / metabolism
  • Signal Transduction
  • Vascular Endothelial Growth Factor C / biosynthesis*


  • Biomarkers
  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Vascular Endothelial Growth Factor C