title: Identification of Commensal Species Positively Correlated with Early Stress Responses to a Compromised Mucus Barrier.
abstract: BACKGROUND
  Our aims were (1) to correlate changes in the microbiota to intestinal gene expression before and during the development of colitis in Muc2 mice and (2) to investigate whether the heterozygote Muc2 mouse would reveal host markers of gut barrier stress.
  
  
  METHODS
  Colon histology, transcriptomics, and microbiota profiling of faecal samples was performed on wild type, Muc2, and Muc2 mice at 2, 4, and 8 weeks of age.
  
  
  RESULTS
  Muc2 mice develop colitis in proximal colon after weaning, resulting in inflammatory and adaptive immune responses, and expression of genes associated with human inflammatory bowel disease. Muc2 mice do not develop colitis, but produce a thinner mucus layer. The transcriptome of Muc2 mice revealed differential expression of genes participating in mucosal stress responses and exacerbation of a transient inflammatory state around the time of weaning. Young wild type and Muc2 mice have a more constrained group of bacteria as compared with the Muc2 mice, but at 8 weeks the microbiota composition is more similar in all mice. At all ages, microbiota composition discriminated the groups of mice according to their genotype. Specific bacterial clusters correlated with altered gene expression responses to stress and bacteria, before colitis development, including colitogenic members of the genus Bacteroides.
  
  
  CONCLUSIONS
  The abundance of Bacteroides pathobionts increased before histological signs of pathology suggesting they may play a role in triggering the development of colitis. The Muc2 mouse produces a thinner mucus layer and can be used to study mucus barrier stress in the absence of colitis.
authors.affiliation: *Top Institute Food and Nutrition, Wageningen, the Netherlands; †Host-Microbe Interactomics Group, Animal Sciences Department, Wageningen University and Research Center, Wageningen, the Netherlands; ‡Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, the Netherlands; §Department of Pediatrics, Academic Medical Center, Amsterdam, the Netherlands; ‖Laboratory of Microbiology, Wageningen University and Research Center, Wageningen, the Netherlands; ¶Division of Human Nutrition, Wageningen University and Research Center, Wageningen, the Netherlands; **NIZO Food Research, Ede, the Netherlands; ††University Medical Center of Groningen, Groningen, the Netherlands; and ‡‡Nutricia Research, Utrecht, the Netherlands.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sovran
authors.forename: Peng
authors.initials: P
authors.lastname: Lu
authors.forename: Linda M P
authors.initials: LM
authors.lastname: Loonen
authors.forename: Floor
authors.initials: F
authors.lastname: Hugenholtz
authors.forename: Clara
authors.initials: C
authors.lastname: Belzer
authors.forename: Ellen H
authors.initials: EH
authors.lastname: Stolte
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.forename: Peter
authors.initials: P
authors.lastname: van Baarlen
authors.forename: Hauke
authors.initials: H
authors.lastname: Smidt
authors.forename: Michiel
authors.initials: M
authors.lastname: Kleerebezem
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Renes
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Wells
authors.forename: Jan
authors.initials: J
authors.lastname: Dekker
mesh_terms: D000818:Animals; D003092:Colitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D055262:Mucin-2 / Q000502:physiology*; D009093:Mucus / Q000378:metabolism / Q000382:microbiology*; D020411:Oligonucleotide Array Sequence Analysis; D013312:Stress, Physiological
chemical_list: C524626:Muc2 protein, mouse; D055262:Mucin-2