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Nod2 is essential for temporal development of intestinal microbial communities
  1. Ateequr Rehman1,
  2. Christian Sina2,
  3. Olga Gavrilova1,
  4. Robert Häsler1,
  5. Stephan Ott2,
  6. John F Baines3,4,
  7. Stefan Schreiber1,2,
  8. Philip Rosenstiel1
  1. 1Institute for Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU) Kiel, Germany
  2. 2Department of General Internal Medicine, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Germany
  3. 3Institute for Experimental Medicine, Christian-Albrechts-University (CAU) Kiel, Germany
  4. 4Max-Planck-Institute for Evolutionary Biology, Plön, Germany
  1. Correspondence to Dr P Rosenstiel, Institute for Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU) Kiel, Schittenhelmstr. 12, Kiel D-24105, Germany; p.rosenstiel{at}


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.

  • Inflammatory bowel disease
  • NOD2
  • microbiota
  • crohn's disease
  • IBD basic research

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  • AR, CS, SS and PR contributed equally to this study.

  • Funding This study was supported by an Infection Network grant of the BMBF (German Ministry for Education and Research) to PR, SO and SS, the DFG grant RO2994/5-1 and the Excellence Clusters Inflammation at Interfaces IRN G and Junior group Evolutionary Genomics and Future Ocean JRG B2.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Medizinische Fakultaet der Christian-Albrechts-Universitaet zu Kiel. All patient-related procedures were approved by the University Hospital ethics committee (B231/98).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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