NOD2, one of major IBD susceptibility genes and bacterial sensor, is a receptor of muramyl dipeptide which is critical constituent of both Gram-positive and Gram-negative bacteria and NOD2 mutations induce damaged epithelial clearance of invasive bacteria, dysfunction of Paneth cells, reduced production of antimicrobial peptide, decreased microbial diversity and beneficial bacteria abundance [64–66]. Here, NOD2 is linked to inflammatory bowel disease.