title: Host genetics and environmental factors regulate ecological succession of the mouse colon tissue-associated microbiota.
abstract: BACKGROUND
  The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier.
  
  
  RESULTS
  Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice.
  
  
  RESULTS
  In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal and submucosal layers correlating with changes in proinflammatory cytokine profiles and a progressive transition from acute to chronic inflammation of the colon. Tissue-associated bacteria levels peaked at day 21 post-DSS and declined thereafter, correlating with recruitment of innate immune cells and development of the adaptive immune response. Histological parameters, immune cell infiltration and cytokine biomarkers of inflammation were indistinguishable between Nod2 and WT littermates following DSS, however, Nod2 KO mice demonstrated significantly higher tissue-associated bacterial levels in the colon. DSS damage and Nod2 genotype independently regulated the community structure of the colon microbiota.
  
  
  CONCLUSIONS
  The results of these experiments demonstrate the integration of environmental and genetic factors in the ecological succession of the commensal flora in mammalian tissue. The association of Nod2 genotype (and other host polymorphisms) and environmental factors likely combine to influence the ecological succession of the tissue-associated microflora accounting in part for their association with the pathogenesis of inflammatory bowel diseases.
authors.affiliation: Novartis Institutes for Biomedical Research, Gastrointestinal Disease Area, Horsham, West Sussex, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Smith
authors.forename: Jay
authors.initials: J
authors.lastname: Siddharth
authors.forename: Ruth
authors.initials: R
authors.lastname: Pearson
authors.forename: Nicholas
authors.initials: N
authors.lastname: Holway
authors.forename: Mark
authors.initials: M
authors.lastname: Shaxted
authors.forename: Matt
authors.initials: M
authors.lastname: Butler
authors.forename: Natalie
authors.initials: N
authors.lastname: Clark
authors.forename: Joanna
authors.initials: J
authors.lastname: Jamontt
authors.forename: Robert P
authors.initials: RP
authors.lastname: Watson
authors.forename: Devika
authors.initials: D
authors.lastname: Sanmugalingam
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Parkinson
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics* / Q000276:immunology; D018988:Bacterial Translocation / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate; D017753:Ecosystem; D004848:Epithelium / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014644:Genetic Variation; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D054892:Metagenome / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics*; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D016207:Cytokines; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D012336:RNA, Ribosomal, 16S; D016264:Dextran Sulfate