What causes Crohn’s disease?

The exact cause of Crohn's disease is unknown. In the past, diet and stress were thought to be the cause, but it has since been discovered that these factors don’t cause but aggravate the disease. 

Now researchers believe Crohn’s disease is caused by a combination of factors, including an overreaction of the immune system, genetics and environmental factors.

The immune system 
The immune system protects us. Normally it is activated when the body is exposed to harmful bacteria, viruses, fungi and other foreign substances. When the immune system is activated, it causes inflammation. Once the substance has been inactivated the immune response ends and the inflammation subsides.

With Crohn's disease however, that the immune response is abnormal. There are a couple of theories pertaining to the cause of the inflammation:

• The proteins sent to disable the harmful substances kill both friendly and harmful bacteria in the gut, causing the inflammation associated with Crohn’s disease.
• Once the immune response to a harmful substance is complete, the inflammatory response does not stop, causing chronic inflammation.
• The immune system is abnormally activated in the absence of an invader, thereby killing the friendly bacteria and causing the inflammation and ulceration.  There have been some studies indicating that this abnormal activation of the immune system is genetically inherited.
• The inflammation is due to an autoimmune reaction where the bacteria in the gut mistakenly trigger an immune response.

There are however still questions as to whether the abnormal immune system causes Crohn's disease or results from it.

Genetics
Some evidence suggests that genetics is involved in Crohn's disease. This evidence comes from family history as well as gene studies.

Crohn’s is more common in people who have family members with the disease. About 10 - 20% of people with Crohn’s disease have a close relative who also has the disease. Identical twin studies have shown that, if you have an identical twin with the condition, you have a 70% chance of developing it.

Crohn’s disease is also more common in certain ethnic groups (for example, people of Jewish descent and Caucasians), which suggests that genetics may play a role.

Researchers have identified more than 200 different genes that are more common in people with Crohn's disease than in the general population.

One of the genes that has been identified helps the body to decide how to react to certain microbes. The mutated gene causes the body's reaction to the microbes to be different from the normal reaction. This abnormal reaction can lead to Crohn's disease developing. People with Crohn's disease have this mutated gene twice as often as people who don’t have the disease.

A gene that’s important in determining how the body responds to bacteria has been identified, and is hypothesised to be associated with Crohn’s disease. People with a mutation in this gene are more prone to developing the condition.

Genes that contribute to macrophage defects have also been identified and linked to Crohn’s. People with this condition have higher levels of E. coli, which are usually eliminated by intestinal macrophages (a type of white blood cell). One theory as to why these people have higher levels of E. coli is that they have a genetically determined defect that interferes with the elimination of the bacteria. 

The exact roles that these various genetic factors play in the development of Crohn’s disease is still unclear.

Environmental factors
Environmental factors, especially those associated with the modern Western lifestyle, may play a role in causing Crohn’s disease. This hypothesis is based on the fact that it is a “disease of the rich” (the highest prevalence of Crohn’s disease is in the developed world, whereas the lowest rate is in the developing world). It also became much more widespread after the 1950s.

There are two available hypotheses:

• The hygiene hypothesis. Children who grow up in a “germ-free” environment don’t develop their immune system fully because of a lack of exposure to childhood infections. There is, however, very little scientific evidence to support this theory.
• The cold-chain hypothesis. The increased use of refrigerators after the Second World War paralleled with an increased prevalence of Crohn’s disease. It is hypothesised that some bacteria that survive in the cold chain are linked to the disease. Again, very little scientific evidence is available to support this hypothesis. 

Other environmental factors that may trigger Crohn's disease include:

• Cigarette smoke. Smokers are twice as likely to develop the condition as non-smokers.
• Substances from certain foods in the diet.
• Infection by certain bacteria (e.g. mycobacterium).
• A high-fat diet (this may slightly increase your chance of getting Crohn’s disease).
• Using non-steroidal anti-inflammatory drugs (e.g. aspirin, ibuprofen), antibiotics and/or birth-control pills may slightly increase your chances of developing the disease.

The environmental factors may contribute to Crohn’s disease by either triggering an immune response that doesn’t stop or by causing direct damage the lining of the gut.

Note: Even though a potential trigger is linked to or associated with a condition, it doesn’t mean that it causes it.

Reviewed by Kim Hofmann, registered dietitian, BSc Medical (Honours) Nutrition and Dietetics, BSc (Honours) Psychology. December 2017.