Crohn’s disease is the number one strange disease of the digestive system: three major symptoms such as abdominal pain, diarrhea, weight loss, and in severe cases, intestinal stricture, enterocutaneous fistula, enterocystic fistula, etc., as well as a variety of extraintestinal manifestations. So, what is the cause of this strange disease? Crohn’s disease was originally reported in 1932 by Crohn (hence the name Crohn’s disease, or CD for short), Ginzburg and Oppenheimer. The main site of Crohn’s disease is the small intestine, and in some cases, the colon may be involved. Therefore, the disease has been known to us for less than 100 years. Crohn’s disease has been studied tirelessly by medical researchers. It is now believed that CD is a complex polygenic and environmentally induced abnormal immune response disease that occurs in susceptible populations. Bacteria? The idea that bacterial infection causes inflammatory bowel disease has been largely rejected. However, Mycobacterium tuberculosis-like DNA has been found in Crohn’s disease tissues, and we can only assume that Mycobacterium tuberculosis-like bacteria play a part in the pathogenesis of Crohn’s disease. Statistics show that there is a clear association between the onset of Crohn’s disease in some patients and the use of antibiotics prior to the onset of the disease, so that alterations in the intestinal bacterial environment in the body may be a causal factor in the disease. Smoking? Smoking may be associated with Crohn’s disease but not ulcerative colitis, and smokers have a significantly increased risk of recurrence after surgery compared to nonsmokers. Genes? Crohn’s disease is found in 60% of identical twins with IBD. The presence of occult small bowel inflammation has been confirmed in first-degree relatives of symptomatic Crohn’s disease patients. Both Crohn’s disease and ulcerative colitis are associated with the DNA repair gene MLH1. The NOD2 gene (now newly named CARD15) is thought to be the IBD1 gene and is located in the perisynaptic region of chromosome 16. Its discovery kicked off a major genetic study of the underlying etiology of IBD. the NOD2 gene acts through the activation of the transcription factor cytosolic factor NF-κB, which plays an important role in the pathogenesis of Crohn’s disease. nod2 encodes a protein corresponding to the plant resistance gene, which plays a role in the immune response of the infected organism, particularly in the leucine-rich region of bacterial lipopolysaccharide binding. 10% of Crohn’s disease patients have a shift code mutation (via cytosine insertion), thus leading to a failure of NF-κB induction in the presence of bacterial lipopolysaccharide, such that the immune response to the bacterial component fails, which can be used to explain the role of antibiotics in the treatment of Crohn’s disease and the value of microecological agents. Thus, in conclusion, the pathogenesis of Crohn’s disease is the result of a combination of genetic and environmental factors.