title: Early colonizing Escherichia coli elicits remodeling of rat colonic epithelium shifting toward a new homeostatic state.
abstract: We investigated the effects of early colonizing bacteria on the colonic epithelium. We isolated dominant bacteria, Escherichia coli, Enterococcus faecalis, Lactobacillus intestinalis, Clostridium innocuum and a novel Fusobacterium spp., from the intestinal contents of conventional suckling rats and transferred them in different combinations into germfree (GF) adult rats. Animals were investigated after various times up to 21 days. Proliferative cell markers (Ki67, proliferating cell nuclear antigen, phospho-histone H3, cyclin A) were higher in rats monocolonized with E. coli than in GF at all time points, but not in rats monocolonized with E. faecalis. The mucin content of goblet cells declined shortly after E. coli administration whereas the mucus layer doubled in thickness. Fluorescence in situ hybridization analyses revealed that E. coli resides in this mucus layer. The epithelial mucin content progressively returned to baseline, following an increase in KLF4 and in the cell cycle arrest-related proteins p21(CIP1) and p27(KIP1). Markers of colonic differentiated cells involved in electrolyte (carbonic anhydrase II and slc26A3) and water (aquaglyceroporin3 (aqp3)) transport, and secretory responses to carbachol were modulated after E. coli inoculation suggesting that ion transport dynamics were also affected. The colonic responses to simplified microbiotas differed substantially according to whether or not E. coli was combined with the other four bacteria. Thus, proliferation markers increased substantially when E. coli was in the mix, but very much less when it was absent. This work demonstrates that a pioneer strain of E. coli elicits sequential epithelial remodeling affecting the structure, mucus layer and ionic movements and suggests this can result in a microbiota-compliant state.
authors.affiliation: 1] INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [2] AgroParisTech, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [3] Commensal and Probiotics-Host Interactions Laboratory, INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Tomas
authors.affiliation: 1] PERITOX, EA 4285 UMI 01 INERIS, UFR of Medecine-UPJV, Amiens, France [2] EGEAL team, UPSP 2007-05-137, Institut Polytechnique La Salle Beauvais, Beauvais, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Reygner
authors.affiliation: 1] INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [2] AgroParisTech, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [3] Commensal and Probiotics-Host Interactions Laboratory, INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Mayeur
authors.affiliation: Inserm UMRS1149, UFR de Médecine Paris 7, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Ducroc
authors.affiliation: 1] INRA, UMR 1313, Animal Genetics and Integrative Biology, F-78350, Jouy-en-Josas, France [2] Laboratory of Radiobiology and Genomics Studies, CEA, DSV, IRCM, SREIT, F-78350, Jouy-en-Josas, France [3] AgroParisTech, UMR 1313, Animal Genetics and Integrative Biology, F-78350, Jouy-en-Josas, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bouet
authors.affiliation: 1] INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [2] AgroParisTech, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [3] Commensal and Probiotics-Host Interactions Laboratory, INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Bridonneau
authors.affiliation: Inserm UMRS1149, UFR de Médecine Paris 7, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Cavin
authors.affiliation: 1] INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [2] AgroParisTech, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [3] Commensal and Probiotics-Host Interactions Laboratory, INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Thomas
authors.affiliation: 1] INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [2] AgroParisTech, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [3] Commensal and Probiotics-Host Interactions Laboratory, INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.affiliation: 1] INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [2] AgroParisTech, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France [3] Commensal and Probiotics-Host Interactions Laboratory, INRA, UMR 1319 MICALIS, F-78350, Jouy-en-Josas, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Cherbuy
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003106:Colon / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D004926:Escherichia coli / Q000502:physiology*; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D000090062:Kruppel-Like Factor 4; D008297:Male; D009077:Mucins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D018797:Cell Cycle Proteins; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D009077:Mucins