Inflammatory bowel disease: pathogenesis
- Mechanism
Crohn disease and ulcerative colitis arise when a gut with a weak barrier and inherited risk genes reacts too strongly to its own bacteria.
What it is
Inflammatory bowel disease (IBD) comprises Crohn disease and ulcerative colitis. Neither has a single cause: they arise from the combined effect of many risk genes, defects in the epithelial barrier and in autophagy, altered gut microbes (dysbiosis) and a mucosal immune response dominated by Th1 and Th17 cells. Most risk genes are shared by both diseases. IBD was most common in North America, northern Europe and Australia but is rising in Latin America, Asia and Africa as lifestyles change.
Step by step
- Genetic variants alter microbial sensing (NOD2), autophagy (ATG16L1, IRGM) or immune regulation (IL-10, IL-23 receptor).
- A leaky epithelial barrier lets luminal microbes and their products reach the lamina propria.
- Dendritic cells and macrophages present microbial antigens and release IL-12 and IL-23.
- Th1 and Th17 cells expand and release IFN-γ, IL-17 and TNF; regulatory control fails.
- Neutrophils and cytokines damage the epithelium, worsening barrier loss: a self-perpetuating loop.
- Repeated cycles of injury and repair produce the chronic architectural changes of IBD.
Selected IBD genes and what they do
| Gene | Function | Disease link |
|---|---|---|
| NOD2 | Intracellular sensor of bacterial cell-wall peptide | Crohn (risk); protective in ulcerative colitis |
| ATG16L1, IRGM | Autophagosome formation | Crohn; abnormal Paneth cells |
| IL23R | Receptor for IL-23 on Th17 cells | Both |
| IL10, IL10RA, IL10RB | Anti-inflammatory signalling | Monogenic very early onset IBD |
| PTPN22 | Lymphocyte signalling | Crohn risk; protective in ulcerative colitis |
Clinical notes
- Smoking raises Crohn risk but is associated with lower ulcerative colitis risk; colitis may start after a person stops smoking.
- An enteric infection sometimes precedes onset, perhaps by triggering immune activation and dysbiosis.
Test yourself
Think of the answer, then tap the question to see it.
What does NOD2 do, and why is it relevant to Crohn disease?
It is an intracellular sensor of bacterial muramyl dipeptide; risk variants impair handling of gut bacteria and raise Crohn risk.
Which T-helper subsets dominate the inflammation of IBD?
Th17 and Th1 cells, driven by IL-23 and IL-12.
Which genes cause monogenic very early onset IBD?
Most often IL10 and the genes for the IL-10 receptor (IL10RA, IL10RB).
Elsewhere in DurgiPedia
- Th1, Th2, Th17, Tfh and Treg
- IL-12 and IL-23
- Interleukin-17
- Pattern recognition: PAMPs, DAMPs, Toll-like receptors
- Immune tolerance and how autoimmunity begins
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Crohn Disease (StatPearls (NCBI Bookshelf), 2025); Ulcerative Colitis (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.