Causes of Inflammatory Bowel Disease

Having inflammatory bowel disease (Crohn's disease and ulcerative colitis are the two main types) can come with a lot of guilt. There are times when you have to rely on loved ones to care for you. You may wonder if something you did caused your disease. You may wonder what caused a flare. Misinformation about the causes of inflammatory bowel disease can feed feelings of guilt or blame.

The fact is that no one knows exactly what causes inflammatory bowel disease. Researchers believe that it may be a result of multiple factors that interact with each other, including:^1,2

• Genes
• Immune system
• Environment

How does the body normally deal with microorganisms in the gut?

Your digestive tract has millions of viruses, yeasts, fungi, and bacteria. As a group, they are called microorganisms. Your body has many defense systems to keep the helpful microorganisms around and fight the harmful microorganisms. For example, your intestines have a special lining. This lining is designed to let water and nutrients into the body, but keep out microorganisms. If harmful microorganisms do enter your body, your immune system fights them so that you do not get sick.^{1, 3-5}

Why do people with Crohn's or UC react differently to gut microorganisms?

The current theory is that inflammatory bowel diseases like Crohn’s disease and ulcerative colitis develop when the immune system overreacts to the microorganisms in the digestive tract. White blood cells, whose job is to fight infection, travel to the intestine to fight harmless microorganisms. The white blood cells stay in the intestines and cause lasting inflammation.^4,5

Researchers believe that inflammatory bowel disease is likely caused by a genetic predisposition (inherited, or passed down from parents to children) combined with environmental factors (including cigarette smoking, where you live, and hygiene) and a dysfunction in the immune system, which is driven by the gut microbiota (the collection of microorganisms that are normally found in the intestines).^4-7

What role does genetics play in Crohn's and ulcerative colitis?

Both Crohn’s disease and ulcerative colitis can run in families. Fifteen percent of people with Crohn’s disease have a family member with inflammatory bowel disease,⁸ and approximately 10-25% of people with ulcerative colitis have a family member with the disease.⁹ 

Children who are diagnosed with Crohn’s disease are more likely than elderly people to have a family history of this disease.⁷ Identical twins are far more likely to both have Crohn’s disease than fraternal twins.¹⁰ These findings indicate that genetics play a part in Crohn’s disease, although researchers point out that some identical twins, who have the same genetic makeup as their siblings, do not develop Crohn's. This suggests that environmental factors also play a role in the development of the disease.²

Researchers think that some people have genes that make them more likely to develop inflammatory bowel disease.³ This is called susceptibility. At least 4 genes have been linked to Crohn’s disease: NOD2, ATG16L1, IRGM, IL23R.¹¹ NOD2 is strongly linked with inflammation in the end of the small intestine (ileum), intestinal narrowing, fistulas, the need for surgery, younger age at onset, and family history.^10,12

Several genes have been linked to ulcerative colitis, including ABCB1, IL10RA, IL10RB, IL23R, IRF5, PTPN2. Some of these genes are involved in the functioning of the intestinal barrier, while others are involved in the function of the immune system.¹³

While uncovering the genetic clues to inflammatory bowel disease is helpful to understand the causation of the disease and potentially identify future treatments, most people with inflammatory bowel disease do not get genetic tests. You probably will not know if you have these genes.¹²

What environmental factors contribute to Crohn's or UC?

Not everyone with these genes develops inflammatory bowel disease. Environmental factors may be necessary to trigger the immune overreaction in a susceptible person. Importantly, environmental factors alone are not enough to cause Crohn’s disease or ulcerative colitis.

It is not known which environmental factors trigger inflammatory bowel disease. This is an area of ongoing research.* Risk factors that have been studied include:

Smoking

Smokers are more than twice as likely as non-smokers to develop Crohn’s disease. Smoking increases complications and recurrence. Therefore, smokers are more likely to need surgery and medications. However, in ulcerative colitis, smoking is correlated with a reduced risk of the disease. The reason for this is unclear.²

Diet

The role of diet in inflammatory bowel disease is very unclear.² Crohn’s disease and ulcerative colitis are more common in people who live a Westernized lifestyle, which includes certain diet patterns. However, no one has found a conclusive link between any particular food or nutrient and inflammatory bowel disease.

Footnote
* Non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics also have been studied in relation to inflammatory bowel disease. Some—but not all—studies show an association between these medications and risk of inflammatory bowel disease or flares. An association does not prove that medications causes inflammatory bowel disease. Furthermore, the practical benefit of this information is unclear, because there are still unanswered questions about dosage, duration of use, and why medications may affect some people but not others.

Footnote sources:

1. Ananthakrishnan AN. Environmental triggers for inflammatory bowel disease. Curr Gastroenterol Rep. 2013;15:302.
2. Ananthakrishnan AN, Higuchi LM, Huang ES, et al. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study. Ann Intern Med. 2012;156:350-359.
3. Crohn’s and Colitis Foundation of America. The facts about inflammatory bowel disease.