title: Transient inflammatory-like state and microbial dysbiosis are pivotal in establishment of mucosal homeostasis during colonisation of germ-free mice.
abstract: The gut microbiota is increasingly recognised as a key-player in defining the health status of the gastrointestinal tract. Recently, we demonstrated that colonisation of healthy germfree mice with a conventional microbiota (conventionalisation) elicits temporal and region specific host-microbe communication responses that lead to the establishment of a microbiota-accommodating homeostatic state within 30 days. Here, the microbiota composition profiles, mucosal transcriptomes and plasma-analytes in germ-free and conventionalised C57/BL 6 J mice were assessed to decipher the features of the distinctive and pivotal events occurring four days after initiation of the conventionalisation process. The dominance of the microbial genera Helicobacter, Sphingomonas and Mucispirillum in the gut microbiota coincided with the transient mounting of proinflammatory responses in the mucosa and the transiently elevated levels of specific (inflammatory) cytokines and amines in plasma. The overrepresented microbes have previously been associated with the potential to cause disease under certain conditions, illustrating that conventionalisation proceeds through a transient state that resembles situations associated with dysbiosis. However, no overt mucosal inflammation was observed, suggesting a pivotal role of the overrepresented bacterial groups in priming and maturation of the immune system during the process of conventionalisation. These findings imply that the transiently elevated relative overgrowth of particular microbial genera functions as pivotal adjuvants to elicit the corresponding proinflammatory cascades, which precede the full maturation of the different arms of the immune system following these events and is required to achieve a microbiota-accommodating homeostasis in healthy animals.
authors: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, the Netherlands Top Institute Food and Nutrition, P.O. Box 557, 6700 AN Wageningen, the Netherlands.
authors: S
authors: S
authors: El Aidy
authors: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, the Netherlands Top Institute Food and Nutrition, P.O. Box 557, 6700 AN Wageningen, the Netherlands Danone Research, Route départementale 128, 91767 Palaiseau, France.
authors: M
authors: M
authors: Derrien
authors: Division of Analytical Biosciences, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden, the Netherlands Netherlands Metabolomics Centre, Einsteinweg 55, 2333 CC Leiden, the Netherlands.
authors: R
authors: R
authors: Aardema
authors: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, the Netherlands.
authors: G
authors: G
authors: Hooiveld
authors: School of Science and Technology, Nottingham Trent University, Clifton Lane A453, Nottingham NG11 8NS, United Kingdom.
authors: S E
authors: SE
authors: Richards
authors: Division of Analytical Biosciences, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden, the Netherlands Netherlands Metabolomics Centre, Einsteinweg 55, 2333 CC Leiden, the Netherlands.
authors: A
authors: A
authors: Dane
authors: Top Institute Food and Nutrition, P.O. Box 557, 6700 AN Wageningen, the Netherlands Department of Animal Sciences, Host Microbe Interactomics Group, Wageningen University, De Elst 1, 6708 WD Wageningen, the Netherlands.
authors: J
authors: J
authors: Dekker
authors: Division of Analytical Biosciences, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden, the Netherlands Netherlands Metabolomics Centre, Einsteinweg 55, 2333 CC Leiden, the Netherlands.
authors: R
authors: R
authors: Vreeken
authors: Commensal and Food Bacteria Group, INRA, UMR1319 Micalis, Domaine de Vilvert, 78350 Jouy-en-Josas, France.
authors: F
authors: F
authors: Levenez
authors: Commensal and Food Bacteria Group, INRA, UMR1319 Micalis, Domaine de Vilvert, 78350 Jouy-en-Josas, France.
authors: J
authors: J
authors: Doré
authors: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, the Netherlands Top Institute Food and Nutrition, P.O. Box 557, 6700 AN Wageningen, the Netherlands.
authors: E G
authors: EG
authors: Zoetendal
authors: Department of Animal Sciences, Host Microbe Interactomics Group, Wageningen University, De Elst 1, 6708 WD Wageningen, the Netherlands.
authors: P
authors: P
authors: van Baarlen
authors: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, the Netherlands Top Institute Food and Nutrition, P.O. Box 557, 6700 AN Wageningen, the Netherlands Department of Animal Sciences, Host Microbe Interactomics Group, Wageningen University, De Elst 1, 6708 WD Wageningen, the Netherlands NIZO food research, Health Department, P.O. Box 20, 6710 BA Ede, the Netherlands.
authors: M
authors: M
authors: Kleerebezem
mesh_terms: D000588:Amines / Q000097:blood; D000818:Animals; D016207:Cytokines / Q000097:blood; D064806:Dysbiosis / Q000276:immunology / Q000382:microbiology; D020869:Gene Expression Profiling; D005856:Germ-Free Life; D016998:Helicobacter / Q000254:growth & development*; D006706:Homeostasis / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology*; D020578:Sphingomonas / Q000254:growth & development*
chemical_list: D000588:Amines; D016207:Cytokines
keywords: conventionalisation; microbiota; plasma cytokines and metabolites; transcriptome