Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease develops in genetically susceptible individuals, often due to gene mutations involving Nucleotide-binding oligomerization domain-containing protein 2, Autophagy-related 16-like 1, and Interleukin-23 receptor.

Environmental exposures, including cigarette smoking, prior gastrointestinal infections such as Salmonella or Campylobacter, and a higher intake of ultra-processed foods, can increase the risk.

These factors may impair epithelial barrier integrity and disturb the gut microbiome, allowing luminal antigens such as bacterial products and metabolites to interact more directly with immune cells.

This causes immune system dysregulation, leading to a loss of tolerance to commensal gut bacteria. As a result, there is exaggerated immune activation against these commensals, causing ongoing inflammation.

Both innate and adaptive immune cells are activated, including T lymphocytes, macrophages, dendritic cells, and neutrophils.

These cells release critical cytokines like tumor necrosis factor-alpha and interleukin-12, promoting a Th1 and Th17 immune response that leads to transmural inflammation.