for Inflammatory Bowel Disease (IBD)

Risk Factors

KEY POINTS:

Knowledge of the causes or risk factors for Crohn’s disease and ulcerative colitis is limited.
Many genes have been shown to be associated with the development of IBD. Research is continuing and the evidence is not clear about which genes are most important.
Studies with identical twins show that even though they share the same genes, in at most half the pairs of twins have IBD. This indicates that in addition to genetic factors there must be factors in the environment that trigger the development of IBD.
It is believed that something in the environment triggers the bowel to mount an abnormal immune response and lead to development of IBD. Many factors have been studied including the diet, earlier health and treatments, specific medicines, and factors such as stress. We do not yet know what the environmental triggers of IBD might be.
Since immune system functioning is important in the development of IBD, there has been research on factors that influence the development of the immune system. Exposure to common microbes (bacteria, viruses, fungi, or protozoa) in childhood is important in the development of the immune system.
The hygiene hypothesis suggests that immune mediated conditions such as asthma, allergies, and IBD are more common now because of less exposure to microbes (especially during childhood) in the modern, more hygienic world. An alternate hygiene hypothesis explanation is that in the modern world factors that could lead to loss of protective microbes (such as from excessive antibiotic use) could lead to IBD. More research is necessary to understand the influence of these factors in IBD.
There are more microbe cells in our body than human cells. These microbes are essential in functions such as digestion of food and our defenses against harmful microbes. One theory about IBD is that there is a change in the balance of healthy and unhealthy microbes in the gut that triggers abnormal inflammation. This is an area of much research interest but there is not yet enough information to draw clear conclusions.
Finding the trigger or triggers for IBD is challenging, as it may be factors acting early in life that lead to IBD much later in life.
Smoking. Persons with Crohn’s disease are more likely to be smokers. Smokers with Crohn’s disease have a more aggressive disease course than nonsmokers. Quitting smoking may improve the disease course. Direct smoking would not be a risk factor for children with IBD, but there is some consideration whether passive smoking would be a risk factor (this refers to nonsmokers getting the effect of smoke from living with smokers who smoke within the house). Smoking as a risk factor is complicated since it is a risk factor in the West but is not a risk factor for Crohn’s disease in Asia.

Genetics

IBD runs in families. A person with IBD has a 20% (2 in 10) chance of having any relative with IBD and a 10% (1 in 10) chance of having a first degree relative (parent, child or sibling) with IBD.
When a person with Crohn’s disease has a relative with IBD, that relative is most likely to have Crohn’s disease, although there is also an increased rate of ulcerative colitis compared to people without IBD. This suggests that the risk for developing Crohn’s disease and ulcerative colitis is shared.
In pairs of identical twins, if one twin has Crohn’s disease there is about a 50% or 5 in 10 chance that the other twin has IBD. If one twin has ulcerative colitis there is a 10% or 1 in 10 chance the other twin has IBD. Since identical twins have identical genes, this suggests that there are both genetic and environmental factors in the development of IBD. The genetic factor is stronger in Crohn’s disease.
Research to this point has identified over 200 gene mutations associated with IBD. Some are shared between Crohn’s disease and ulcerative colitis and some are unique. As there are many thousand human genes, future research will likely identify even more genes associated with IBD. Some of the genes increase the risk for IBD while others decrease the risk and it is likely that different genes or groups of genes are influential in different people with IBD. A person with IBD may have one or several mutations in these identified genes. On the other hand, there may be no mutation in any of these genes.
In the long run, understanding the genes associated with IBD and the proteins they produce may help us understand the development of IBD and what treatments might be most helpful. Having a gene mutation, though, that is related to IBD is not sufficient to cause IBD.
While genetic tests are available for some diseases, no practical genetic test exists for IBD at this point. It is likely that tests that provide helpful information for some forms of IBD will become available in the future.

Diet

Since bowel symptoms are prominent in IBD, it is reasonable that diet would be considered as a factor in the development of IBD. As IBD is more common in North America and more developed countries and is increasing in developing countries, there has been concern that the diet in developed countries may be a factor in development in IBD.
Greater consumption of some foods is associated with the risk for developing IBD. This includes greater consumption of meat and fats, particularly polyunsaturated fatty acids (PUFAs) and omega-6 (n-6) fatty acids. There is lower risk among people with diets high in fiber, fruits, and vegetables. There has been limited research on these aspects of diet when IBD is present.
There are dietary measures that can help enhance the health of persons with IBD. These are covered in the fact sheet “Nutrition and inflammatory bowel disease (IBD)”.
Once diagnosed with IBD each person may find that different foods trigger their symptoms, so there is no one food group to recommend that persons with IBD specifically should avoid.

Microbes in the gastrointestinal (GI) tract

There are more microbe cells (bacteria, viruses, fungi, or protozoa) in our body than human cells. These microbes are essential in functions such as digestion of food and our defenses against harmful microbes. One theory about IBD is that there is a change in the balance of healthy and unhealthy microbes in the gut that triggers abnormal inflammation.
The types of microbes in our GI system are also influenced by our diet.
This is a strong area of research interest but there is not enough information yet to decide how changes in the GI microbes impact on IBD.
There is some evidence that use of antibiotics can predispose to developing IBD. Antibiotics can be very important and necessary treatments; however, their use should be limited to definite infections that warrant their use.
This research is challenging because there is a tremendous number of species (or kinds) of microbes in our body and the functions of the various species are not well understood. The mix of the types of microbes differs at different points in the GI tract. It is only recently that there have been methods available to study this system.

Medications

Antibiotics. Antibiotics have been clearly associated with developing IBD. Children with IBD are more likely to have received antibiotics in the years before the development of IBD than children without IBD. This is also true for adults. It has not been shown that any specific class of antibiotics is at issue. One possibility is that the use of antibiotics has an influence on the microbes in the gut.
Using antibiotics when necessary. Even though antibiotic use is a risk factor for developing IBD, it is important to continue to use them when recommended by your doctor, as the benefits should outweigh the risks. However, unnecessary use should be avoided.
Nonsteroid anti-inflammatory drugs (NSAIDs) including common pain medicines such as ibuprofen and naproxen (Advil, Motrin, Aleve, Naprosyn) as well as acetylsalicylic acid (ASA, Aspirin) were thought to be associated with worsening IBD symptoms at one time. More recent studies have found no evidence that the use of these drugs can cause IBD. Some persons, though have identified that their IBD seemed to start after using NSAIDs. Whether NSAIDs can worsen IBD still remains a matter of debate. When some people without IBD use these medicines regularly they can cause stomach irritation and even ulcers in the stomach or bowel. So use of these drugs that is more than occasional should be discussed with your doctor.
Isotretinoin (Accutane). There are lawsuits in North America alleging that this drug, used to treat acne, has caused IBD. Large community studies have NOT shown any association between use of isotretinoin and the development of IBD.
Cancer immunotherapy. This type of therapy with drugs that block a protein called CTLA-4 or another protein called PD-1 has revolutionized the treatment of some malignant cancers like melanoma and kidney cancer. These drugs can cause a form of inflammatory bowel disease. It is unknown how often the inflammation in the bowel can become chronic, but it is known that sometimes it can become chronic like IBD. It is typically treated with steroids and sometimes even anti-TNF. It is unknown if persons with IBD who receive these cancer therapies are at increased risk of bowel damage from them or not.

Vaccines

Some people have been concerned that giving their children vaccines could cause a variety diseases including IBD. There is no evidence that this is true.
One study published in the 1990s suggested a link between vaccination and IBD. This research was later found to be fraudulent. Recently a study from Manitoba, Canada found no association between childhood vaccination and the development of IBD.
Recommended vaccines are highly beneficial in reducing serious diseases. Negative effects are rare. Following vaccine schedules is important to maintain the health of children and adults.

Stress

People with IBD often report that their symptoms increase during periods of high stress. There is no evidence that stress causes IBD. Feeling highly stressed is associated with increased symptoms in persons with IBD, but there is no evidence that high stress is associated with active inflammation in the bowel.
Feeling very ill is a significant stress for most people.
There is some interesting evidence that persons with IBD are more likely to have had diagnoses of depression long before their diagnosis of IBD. This raises the question whether having depression can predispose to IBD or whether it simply shares a similar trigger with IBD

Early Childhood

It has been shown that the use of antibiotics or the presence of early life infections have been shown to be risk factors for developing IBD.
Very early life events such as maternal infections prior to birth or at the time of birth, mode of delivery (i.e. by cesarean section versus vaginal delivery), or perinatal markers of health (ie. Birthweight, APGAR score, gestational age) do not impact on the risk of IBD.
It is possible that the timing of introduction of certain foods to babies may impact on their developing gut microbiome especially in the first yer of life and this could impact positively or negatively on the risk for IBD.

Concluding comment: It can be frustrating for persons with IBD that there ar no definite risk factors that are known that will definitely trigger IBD. This is especially so for persons who would like to know what to advise their loved ones to avoid to minimize the likelihood that they would get IBD. Hence, much more research is necessary.

References

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Bernstein CN, Burchill C, Targownik LE, Singh H, Roos LL. Events within the first year of life, but not the neonatal period, affect risk for later development of inflammatory bowel diseases. Gastroenterology 2019; 156(8):2190-2197.

Bernstein CN, Nugent Z, Longobardi T, Blanchard JF. Isotretinoin is not associated with inflammatory bowel disease: A population based case control study. American Journal of Gastroenterology 2009;104:2774-2778.

Bernstein CN, Shanahan F. Disorders of a modern lifestyle– reconciling the epidemiology of inflammatory bowel diseases. Gut 2008; 57:1185-91.

Bernstein CN, Singh S, Graff LA, Walker JR, Miller N, Cheang M. A prospective population-based study of symptomatic triggers of flares in IBD. American Journal of Gastroenterology 2010; 105:1994-2002.

Dixon LJ, Kabi A, Nickerson KP, McDonald C. Combinatorial effects of diet and genetics on inflammatory bowel disease pathogenesis. Inflammatory Bowel Diseases. 2015;21(4):912-922.

Khalili H, Ananthakrishnan AN, Higuchi LM, et al. Early life factors and risk of inflammatory bowel disease in adulthood. Inflamm Bowel Dis. 2013 Mar;19(3):542-7.

McGovern DP, Kugathasan S, Cho JH. Genetics of inflammatory bowel diseases. Gastroenterology 2015;149(5):1163-1176.

Racine A, Carbonnel F, Chan SS, et al. Dietary Patterns and Risk of Inflammatory Bowel Disease in Europe: Results from the EPIC Study. Inflamm Bowel Dis. 2016 Feb;22(2):345-54

Singh S, Graff LA, Bernstein CN. Do NSAIDs, antibiotics, infections or stress trigger flares in IBD? American Journal of Gastroenterology 2009; 104:1298-313.

Tjonneland A, Overvad K, Bergmann MM, et al. Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study. Gut. 2009 Dec;58(12):1606-11.

Ungaro R, Bernstein CN, Gearry R, Hviid A, Kolho KL, Kronman M, Shaw S, Van Kruiningen H, Colombel JF. Antibiotics associated with increased risk of new onset Crohn's disease but not ulcerative colitis: A meta-analysis. American Journal of Gastroenterology 2014; 109: 1728-1738.

Walker JR, Ediger JP, Graff LA, Greenfeld JM, Clara I, Lix L, Rawsthorne P, Miller N, Rogala L, McPhail C, Bernstein CN. The Manitoba IBD Cohort Study: A population-based study of the prevalence of lifetime and twelve-month anxiety and mood disorders. American Journal of Gastroenterology 2008; 103:1989-97.

Last reviewed: March 2020

For more information and fact sheets about IBD and its treatment please visit: http://www.crohnsandcolitis.ca

Disclaimer: This information is provided for educational purposes only. Always consult a qualified health care professional for your specific care.

Source: This summary provides scientifically accurate information. It was prepared in a research review by researchers with the IBD Clinical and Research Centre, University of Manitoba with assistance from colleagues in Canada and internationally. Acknowledgement: Preparation of this material was supported by funding from the Canadian Institutes of Health Research.

©2016 Charles N. Bernstein, John R. Walker on behalf of Manitoba IBD Clinical and Research Centre. This work is licensed under a Creative Commons Attribution-nonCommercial-NoDerivs 2.5 Canada License. You are free to copy and distribute this material in its entirety as long as: 1) this material is not used in any way that suggests we endorse you or your use of the material, 2) this material is not used for commercial purposes, 3) this material is not altered in any way (no derivative works). View full license at http://creativecommons.org/licenses/by-nc-nd/2.5/ca/.