Stappenbeck TS, Hooper LV, Gordon JI.. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 99: 15451-15455

Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2002; 99(24):15451-5. DOI: 10.1073/pnas.202604299
Source: PubMed


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.

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    • "Fourth, the mother supplies milk substances that encourage the appropriate bacterial mix. The bacteria of the gut in particular are critical in the final stages of the organogenesis of the gut capillaries (Stappenbeck et al. 2002) and gut associated lymphoid tissues (Rhee et al. 2004; Niess et al. 2008; Round et al. 2010). Bacteroides, Bifidobacteria, Bacillus species are especially important for the proper induction of these tissues, and it appears that the mother helps them to prosper inside her infant's gut. "
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