RT Journal Article
SR Electronic
T1 Nod2 is essential for temporal development of intestinal microbial communities
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1354
OP 1362
DO 10.1136/gut.2010.216259
VO 60
IS 10
A1 Ateequr Rehman
A1 Christian Sina
A1 Olga Gavrilova
A1 Robert Häsler
A1 Stephan Ott
A1 John F Baines
A1 Stefan Schreiber
A1 Philip Rosenstiel
YR 2011
UL http://gut.bmj.com/content/60/10/1354.abstract
AB 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.