Thus CARD15/NOD2 polymorphism is associated with an inappropriate immune response to intestinal bacteria, which in turn leads to quantitative or qualitative changes in the bacterial population in the intestinal lumen or lamina propria, causing inflammation. CARD15/NOD2 mutations have been shown to lead to decreased intestinal production of α-defensins by Paneth cells and to a loss of immune response to pathogens. CARD15/NOD2 dysfunction has also been shown to lead to the development of CD by inducing changes in the intestinal microflora, thereby affecting immune effectors. This evidence concerns the gene NOD2 and Cowden disease.