Mutations in the leucine-rich repeat (LRR) domain of Nod2, a bacterial recognition protein, are associated with development of the inflammatory bowel disorder, Crohn's disease.
Recent studies have implicated Single Nucleotide Polymorphisms (SNPs) of the NOD2/CARD15 gene with the onset of several Inflammatory Bowel Disorders (Crohn's Disease, Blau syndrome) and the progression of several malignant diseases.
Our results demonstrate that NOD2 has an unexpected role in shaping a protective assembly of gut bacterial communities and suggest that manipulation of dysbiosis is a potential therapeutic approach in the treatment of human intestinal disorders.
Mutations of the caspase-activating recruitment domain 15 (CARD15) gene on chromosome 16 are associated with chronic inflammatory granulomatous bowel disease (Crohn's disease).
Crohn's disease is a chronic inflammatory bowel disorder that has been associated with polymorphisms in the genes encoding the pattern-recognition receptor NOD2 and the autophagic regulator ATG16L1.
These findings reveal a novel inhibitory interaction between TLR4 and NOD2 signaling in enterocytes leading to the regulation of enterocyte apoptosis and suggest a therapeutic role for NOD2 in the protection of intestinal diseases such as NEC.