Primocolonization is associated with colonic epithelial maturation during conventionalization

FASEB J. 2013 Feb;27(2):645-55. doi: 10.1096/fj.12-216861. Epub 2012 Nov 1.


Interaction between the gut microbiota and the host starts immediately after birth with the progressive colonization of the sterile intestine. Our aim was to investigate the interactions taking place in the colonic epithelium after the first exposure to gut microbiota. Germ-free (GF) rats were inoculated with two different microbiotas: the first, obtained from suckling rats, was rich in primocolonizing bacteria and the second, obtained from adult rats, was representative of a mature microbiota. Once transferred into GF rats, these two microbiotas evolved such that they converged, and recapitulated the primocolonization pattern, mimicking the chronological scheme of implantation following birth. The two microbiotas induced common responses in the colonic epithelium: a transitory proliferative phase followed by a compensatory phase characterized by increases in the abundance of p21(Cip1) and p27(Kip1) and in the number of goblet cells. The effects of the two microbiotas diverged only through their effects on colonic transporters. Analyses of solute carriers and aquaporins revealed that functional maturation was more pronounced following exposure to adult microbiota than suckling microbiota. The colon matured in parallel with the evolution of the microbiota composition, and we therefore suggest a link between intestinal events regulating homeostasis of the colon and modulation of microbial composition.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Colon / growth & development*
  • Colon / metabolism
  • Colon / microbiology*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • DNA, Bacterial / genetics
  • DNA, Bacterial / isolation & purification
  • Genes, Bacterial
  • Germ-Free Life
  • Intestinal Mucosa / growth & development
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Male
  • Metagenome* / genetics
  • Rats
  • Rats, Inbred F344
  • Time Factors


  • Cdkn1a protein, rat
  • Cdkn1b protein, rat
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA, Bacterial
  • Cyclin-Dependent Kinase Inhibitor p27