NOD2 influences intestinal microbial resilience after antibiotic perturbation

Loss-of-function variants in the nucleotide-binding oligomerization domain-2 (NOD2) gene, impairing the recognition of the bacterial cell wall component muramyl-dipeptide, are associated with an increased risk for developing Crohn's disease (CD). A disturbed control of gut microbial communities is hypothesized as a causative mechanism contributing to increased susceptibility for chronic intestinal inflammation through this genetic variation. In this study, we demonstrate the influence of NOD2 on the longitudinal dynamics of the intestinal microbiota using wild-type C57BL/6J and knock-out NOD2 mice treated with broad-spectrum antibiotics. Sequencing of the 16S rRNA gene and ITS1 region revealed that antibiotics caused significant long-term shifts in the bacterial and fungal community composition. Importantly, we demonstrate a phenotypic variation, where the NOD2 genotype impairs resilience of the bacterial gut microbiota leading to a delayed recovery. These results provide evidence of the role of NOD2 for controlling resilience of the intestinal microbiota, and suggest that uncontrolled dynamics of intestinal microbiota after perturbation could be involved in the etiology of IBD.