From carrier to responder - few commensals restore immunocompetence in adult germfree mice via maturation of the intestinal vascular system

The intestinal microbiota fundamentally influences the development of a normal intestinal physiology and education and functioning of the mucosal immune system. Using the C. rodentium carrier model of germfree mice (GF), we found that colonization of adult GF with 14 selected commensals (OMM12+MC2) was sufficient to convert a carriers into responders through maturation of intestinal crypts, increasing intestinal angiogenesis and stimulation of the immune system. While the immature colon of C. rodentium infected GF did not allow sufficient extravasation of neutrophils into the gut lumen, colonization with these commensals triggered activation and proliferation of endothelial cells, enabling granulocytes to transmigrate into the gut lumen. Enhanced angiogenesis and morphological maturation development of the intestine was most likely due to sensing of commensals by Paneth cells and subsequent secretion of antimicrobial peptides and angiogenetic factors. This demonstrates the therapeutic value of few commensal bacteria to complete morphological and immunological maturation in of the adult intestinal mucosa enabling rendering this organ immunocompetent against infections and responsive to therapies. Overall design: Endothelial cells from germ free and conventional mice were analyzed for mRNA profiles