Crohn’s
disease (CD) is an intestinal inflammatory disease with unknown etiology, and its morbidity mechanism is complex, involving the interaction of multiple factors.
Genetic factors
Several
studies have shown that Crohn’s disease has a clear genetic predisposition. Familial aggregation studies have found that the risk of morbidity in people with family history of Crohn’s disease is significantly higher than that in the general population. Several genetic loci associated with Crohn’s disease have been identified, such as the NOD2/CARD15 gene. This gene plays an important role in intestinal immune defense, and its mutation can lead to abnormal recognition and response of intestinal mucosa to intestinal flora, which makes the body produce excessive immune response to normal intestinal flora and cause intestinal inflammation. In addition, there are many other genes involved, which may be related to immune regulation, intestinal mucosal barrier function and so on, and their abnormalities increase the risk of morbidity of Crohn’s disease.
Immune factors
Abnormal activation of the
immune system plays a central role in the morbidity of Crohn’s disease. Under normal circumstances, the intestinal immune system can maintain tolerance to a large number of antigens in the intestine, including intestinal flora and food antigens. However, in patients with Crohn’s disease, this immune tolerance is broken. On the one hand, innate immune response is enhanced, and immune cells such as macrophages and dendritic cells in intestinal mucosa are over-activated. After recognizing the molecular patterns associated with intestinal flora, they will release a large number of inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc. These inflammatory factors can further activate other immune cells and inflammatory signaling pathways. On the other hand, the adaptive immunity is also disordered, the helper T cell (Th) subsets are unbalanced, the number of Th1 and Th17 cells is increased and their functions are hyperactive, the cytokines secreted by them aggravate the intestinal inflammatory response, and the function of regulatory T cells (Treg) is impaired, which can not effectively inhibit the immune response, resulting in the persistence and development of intestinal inflammation.
Intestinal dysbacteriosis
Intestinal flora plays an important role in the morbidity of Crohn’s disease. Normal intestinal flora maintains a symbiotic relationship with the host, participating in the host’s nutritional metabolism, immune regulation and other physiological functions. In patients with Crohn’s disease, the composition and diversity of intestinal flora are altered, with a decrease in beneficial bacteria and an increase in potentially pathogenic bacteria. This flora imbalance may affect the intestinal immune system through a variety of ways, such as some bacterial components can activate the intestinal mucosal immune system and trigger inflammatory response. Moreover, dysbacteriosis may interact with genetic factors, and individuals with genetic susceptibility are more likely to morbidity in the case of intestinal flora disorders.
Environmental factors
Environmental factors also play a role in the morbidity of Crohn’s disease. For example, smoking is an important risk factor for Crohn’s disease, which can increase the risk of morbidity, recurrence and operation. Dietary factors can not be ignored, long-term high-sugar, high-fat, high-animal protein Western dietary patterns may change the intestinal flora, thereby affecting the intestinal immune function, and promote the occurrence and development of Crohn’s disease. In addition, psychological factors such as life stress may affect intestinal immune status through neuro-endocrine-immune network, which is related to the morbidity of Crohn’s disease.
In conclusion, the morbidity of Crohn’s disease is the result of the interaction of genetic, immune, intestinal flora and environmental factors, which form a complex network and together lead to chronic intestinal inflammation.
