NOD2 and bacterial recognition as therapeutic targets for Crohn's disease

Crohn's disease (CD) is a chronic, disabling disease of the gastrointestinal tract that mostly affects young adults. Despite extensive research, the pathogenesis of CD is still not completely understood. It is thought that an abnormal mucosal immune response is elicited towards the luminal microbiota in genetically predisposed persons. Genome-wide association studies and meta-analysis have greatly improved our insight into the genetic background of CD. One of the most studied CD-associated genes is nucleotide-binding oligomerization domain 2 (NOD2). Areas covered: We summarize the current knowledge about NOD2, its use in clinical practice, the functional implications of NOD2 mutations and the therapeutic options for targeting NOD2 in CD. Expert opinion: Almost 2 decades after the identification of NOD2 variants in CD, it has become clear that wild type NOD2 is involved in preserving intestinal barrier integrity and immune homeostasis, properly functioning autophagy and balancing the gut microbiota composition. Given the high prevalence and effect size of NOD2 risk alleles in patients with CD and their interplay with important molecular pathways involved in the disease, NOD2 should seriously be considered as a therapeutic target for CD. Several therapeutic approaches exist and these should be further explored to treat NOD2-related deficiencies in CD.