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 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.
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.
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.
Mutations of the caspase-activating recruitment domain 15 (CARD15) gene on chromosome 16 are associated with chronic inflammatory granulomatous bowel disease (Crohn's disease).