[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Gastrointestinal tract](https://durgical.com/en/general-pathology/areas/gi/) › Inflammatory bowel disease: pathogenesis

# 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.

Updated Nov 12, 2026

## Key points

- More than two hundred risk loci, but together they explain only a small part of the risk; NOD2 (a sensor of bacterial muramyl dipeptide) is the classic Crohn gene.
- NOD2 and PTPN22 variants raise Crohn risk but protect against ulcerative colitis.
- Autophagy genes ATG16L1 and IRGM: defective handling of intracellular bacteria; abnormal Paneth cell granules.
- Very early onset (infantile) IBD can be monogenic: IL10 and IL10 receptor mutations.
- Th17 and Th1 cells dominate; IL-23 and IL-12 drive them; anti-TNF, anti-IL-12/23, anti-IL-23, anti-integrin and JAK-inhibitor therapies all target this axis.
- Hygiene hypothesis: less early microbial exposure may weaken mucosal regulation.

## 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](https://durgical.com/en/conditions/crohn-disease/) | Intracellular sensor of bacterial cell-wall peptide | Crohn (risk); protective in ulcerative colitis |
| [ATG16L1, IRGM](https://durgical.com/en/conditions/crohn-disease/) | 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.

## Memory aid

Genes load the gun, a leaky wall opens the door, microbes walk in, and Th17 pulls the trigger.

## 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).

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## Elsewhere in DurgiPedia

- [Th1, Th2, Th17, Tfh and Treg](https://durgical.com/en/immunology/th1-th2-th17-tfh-and-treg/)
- [IL-12 and IL-23](https://durgical.com/en/immunology/il-12-and-il-23/)
- [Interleukin-17](https://durgical.com/en/immunology/interleukin-17/)
- [Pattern recognition: PAMPs, DAMPs, Toll-like receptors](https://durgical.com/en/immunology/pattern-recognition-pamps-damps-toll-like-receptors/)
- [Immune tolerance and how autoimmunity begins](https://durgical.com/en/immunology/immune-tolerance-and-how-autoimmunity-begins/)

## Connections

## Related 5

- [Crohn disease](https://durgical.com/en/general-pathology/crohn-disease/)
- [Ulcerative colitis vs Crohn disease](https://durgical.com/en/general-pathology/ulcerative-colitis-vs-crohn-disease/)
- [Colitis-associated neoplasia: dysplasia in long-standing IBD](https://durgical.com/en/general-pathology/colitis-associated-neoplasia-dysplasia-in-long-standing-ibd/)
- [Autophagy](https://durgical.com/en/general-pathology/autophagy/)
- [Chronic inflammation: causes, cells and features](https://durgical.com/en/general-pathology/chronic-inflammation-causes-cells-and-features/)

## Related conditions 3

- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)
- [Ulcerative colitis](https://durgical.com/en/conditions/ulcerative-colitis/)
- [Primary sclerosing cholangitis](https://durgical.com/en/conditions/primary-sclerosing-cholangitis/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://www.ncbi.nlm.nih.gov/books/NBK436021/) (StatPearls (NCBI Bookshelf), 2025); [Ulcerative Colitis](https://www.ncbi.nlm.nih.gov/books/NBK459282/) (StatPearls (NCBI Bookshelf), 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/inflammatory-bowel-disease-pathogenesis/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/inflammatory-bowel-disease-pathogenesis/