Inflammatory Bowel Diseases (IBD), includes Crohn's disease and ulcerative colitis, are characterised by chronic, relapsing inflammation of the gastrointestinal tract. The pathogenesis of IBD is complex and multifactorial, involving genetic susceptibility, environmental influences, gut microbiota, and immune dysregulation. One of the primary hypotheses is that a dysfunctional immune response to commensal microorganisms in the gut leads to a loss of mucosal tolerance, resulting in excessive inflammation.1,2
A significant advancement in understanding IBD pathogenesis is the identification of genetic factors. Over 160 susceptibility gene loci have been associated with IBD, particularly genes involved in immune regulation and epithelial barrier function.2,3 NOD2, the first identified gene associated with Crohn’s disease, plays a critical role in recognising bacterial components and triggering an immune response.2 Mutations in NOD2 lead to impaired autophagy and bacterial clearance, contributing to chronic intestinal inflammation and dysbiosis (community of microogranisms). 3 Equally important is the role of the gut microbiota. IBD patients often exhibit dysbiosis, characterised by a reduced diversity of beneficial microbes and an increase in pathogenic bacteria.2 This microbial imbalance makes inflammation worse by disrupting the epithelial barrier, allowing bacterial products to creep past the mucosa and trigger an immune response.1 Studies have shown that certain species, such as Faecalibacterium prausnitzii, have anti-inflammatory properties and are reduced in patients with Crohn’s disease.3
Finally, environmental factors, including diet and smoking, play a role in modulating disease onset and progression. Smoking has a protective effect in ulcerative colitis but increases the risk for Crohn’s disease.2 The interaction between these environmental triggers and genetic susceptibility is key to understanding the complex mechanisms driving IBD pathogenesis.
In conclusion, IBD arises from a convergence of genetic, microbial, and environmental factors, with immune system dysregulation serving as the central mediator of chronic inflammation. Further research into these interactions holds promise for identifying novel therapeutic targets.1,2,3
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