title: Nod2 is essential for temporal development of intestinal microbial communities.
abstract: OBJECTIVE
  The mammalian commensal gut microbiota is highly diverse and displays an individual-specific composition determined by host genotype and environmental factors. The temporal development of host-microbial homeostasis in the digestive tract is recognised as a major function of the immune system. However, the underlying cellular and molecular mechanisms are just beginning to come to light. Nucleotide-binding, oligomerisation domain 2 (NOD2) recognises bacterial muramyl dipeptide and is regarded as a pivotal sensor molecule of the intestinal barrier. The aim of this study was to investigate its influence on the development and composition of the intestinal microbiota using a Nod2-deficient mouse model.
  
  
  METHODS
  The dynamics of faecal and ileal microbial composition were investigated in Nod2(+/+)and Nod2(-/-) mice on a C57BL/6J background. We assessed microbial diversity and composition using 16S ribosomal RNA gene-based clone library sequencing and high throughput pyrosequencing and quantified the observed changes by real-time PCR. Changes in the major bacterial phyla were investigated in human samples by quantitative real-time PCR.
  
  
  RESULTS
  We found that adult Nod2-deficient mice display a substantially altered microbial community structure and a significantly elevated bacterial load in their faeces and terminal ileum compared to their wild-type counterparts. Interestingly, we demonstrate that these findings are also present in weaning mice, indicating a profound influence of Nod2 on the early development and composition of the intestinal microbiota. We demonstrate that NOD2 genotypes also influence the microbial composition in humans.
  
  
  CONCLUSIONS
  Our results point to an essential role of Nod2 for the temporal development and composition of the host microbiota, both in mice and in humans, which may contribute to the complex role of NOD2 for the aetiopathogenesis of Crohn's disease.
authors.affiliation: Institute for Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU) Kiel, Germany.
authors.forename: Ateequr
authors.initials: A
authors.lastname: Rehman
authors.forename: Christian
authors.initials: C
authors.lastname: Sina
authors.forename: Olga
authors.initials: O
authors.lastname: Gavrilova
authors.forename: Robert
authors.initials: R
authors.lastname: Häsler
authors.forename: Stephan
authors.initials: S
authors.lastname: Ott
authors.forename: John F
authors.initials: JF
authors.lastname: Baines
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D058491:Bacterial Load; D001706:Biopsy; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005838:Genotype; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D054892:Metagenome; D051379:Mice; D008807:Mice, Inbred BALB C; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D053473:Nod2 Signaling Adaptor Protein; D012336:RNA, Ribosomal, 16S