Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells

Thaddeus S. Stappenbeck, Lora V. Hooper, Jeffrey I. Gordon

Research output: Contribution to journalArticle

676 Scopus citations

Abstract

The adult mouse intestine contains an intricate vascular network. The factors that control development of this network are poorly understood. Quantitative three-dimensional imaging studies revealed that a plexus of branched interconnected vessels developed in small intestinal villi during the period of postnatal development that coincides with assembly of a complex society of indigenous gut microorganisms (microbiota). To investigate the impact of this environmental transition on vascular development, we compared the capillary networks of germ-free mice with those of ex-germ-free animals colonized during or after completion of postnatal gut development. Adult germ-free mice had arrested capillary network formation. The developmental program can be restarted and completed within 10 days after colonization with a complete microbiota harvested from conventionally raised mice, or with Bacteroides thetaiotaomicron, a prominent inhabitant of the normal mouse/human gut. Paneth cells in the intestinal epithelium secrete antibacterial peptides that affect luminal microbial ecology. Comparisons of germ-free and B. thetaiotaomicron-colonized transgenic mice lacking Paneth cells established that microbial regulation of angiogenesis depends on this lineage. These findings reveal a previously unappreciated mechanism of postnatal animal development, where microbes colonizing a mucosal surface are assigned responsibility for regulating elaboration of the underlying microvasculature by signaling through a bacteria-sensing epithelial cell.

Original languageEnglish (US)
Pages (from-to)15451-15455
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number24
DOIs
StatePublished - Nov 26 2002

Keywords

  • Ecology
  • Gnotobiotics
  • Small intestine
  • Symbiosis

ASJC Scopus subject areas

  • General

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