What Causes Inflammatory Bowel Disease?

 By Michael Chiorean, MD **

Ulcerative colitis and Crohn’s disease are the most common forms of inflammatory bowel disease (IBD). While the cause of IBD is unknown, there are a number of hypotheses trying to explain an association between changes in the environment, genetics and immune dysregulation and the development of IBD. Although a definitive explanation is lacking, the environment is likely to play an important role since nothing else can have such a dynamic nature that explains the increased frequency of IBD over the last few decades. The human genes, in comparison, have not changed substantially in the last 25,000 years.

Diet
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Diet, the Western kind in particular, is usually a primary suspect. Consumption of a diet rich in red meats, in contrast to a vegetarian diet, may be a risk factor. How diet can change the gut bacteria or the immune system in a way to promote IBD is unclear. Furthermore, despite false claims in social media, there is no diet that can improve or “cure” IBD, with the exception of artificial (elemental) diet in young children. Due to its poor taste, this often has to be given through feeding tubes directly in the stomach which is very poorly tolerated long term. It is advisable that patients with IBD follow a generally healthy diet, including a balanced intake of meats, fruits and vegetables. Favoring lean meats, such as fish or chicken, over red meat may be good advice. In contrast, other nonconventional diets such as the special carbohydrate diet or restrictive diets may be detrimental by leading to malnutrition, sometimes severe. Lactose (dairy)-free or gluten-free diets are generally better tolerated, without being necessarily safer or healthier for patients with IBD. There is also no harm in these diets, so patient preference may play a role in this choice.

Drugs
Other possible risk factors that have been the subject of debate are certain drugs such as non-steroidal anti-inflammatory drugs (NSAIDs, like aspirin and ibuprofen) and oral contraceptives; the use of both has increased substantially in the last century. While the association of chronic NSAID use with flares of IBD appears certain, no such certainty exists in regards to contraceptive use and, therefore, no specific recommendations exist. I tend to reassure my patients in regards to contraceptives and let them choose the method that best fits their lifestyles. We have to remember that these are some of the most commonly used medications worldwide, while the number of IBD cases remains relatively small (approximately 1 in 500 people in the U.S.).

Smoking
MP900341702Smoking is a definite risk factor for Crohn’s disease, while it may be somewhat protective against ulcerative colitis. The harmful effects of smoking are evident not only in Crohn’s disease but also in an increased risk of almost every cancer, as well as heart disease, stroke and dementia. Smokers with inflammatory bowel disease, and Crohn’s patients in particular, should make every effort to quit.

Stress
Stress is ubiquitous as a consequence of our increasingly busy, productive and sometimes chaotic lives. It has been linked to a large number of diseases, called psychosomatic disorders, as well as IBD. Stress may cause disease exacerbations in certain predisposed individuals. There have been studies describing disease flares related to natural disasters, and I occasionally see patients who have predictable flares around stressful events, such as final exams. A stress-free world is not only unrealistic, but medications that help relieve stress, such as anti-anxiety drugs, have no effect on IBD flares – even in patients who experience high anxiety levels related to their diseases or lifestyles. That said, the majority of patients can learn to cope with stress with or without medical assistance, and this leads to an improved quality of life.

Genes
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There is no human disease where genes have not been incriminated at least to some extent. In fact, we are the expression of a complicated genetic code which has been developed and perfected over millions of years. There are more than 25,000 genes in the human body and the genetic material present in every human cell, if stretched in a single string, is several miles long. So it comes as no surprise that certain genetic “accidents” happen and some of them may predispose a person to IBD. More than 100 genes have been associated with Crohn’s disease and almost 50 with ulcerative colitis, with some overlap between the two. This means genes alone are probably not the most important factor in IBD, otherwise we would have only one or two genes responsible, like with hemochromatosis or cystic fibrosis. There is probably more than one way for people to get IBD, which is a topic of intense research these days. The bottom line is that IBD as a whole is only weakly hereditary. In fact, less than 10 percent of first degree relatives of patients with IBD also carry the disease, a little more in Crohn’s than ulcerative colitis. Even in identical twins the concordance rate is only 30 percent for Crohn’s and about half that for ulcerative colitis.

In conclusion, we may not know what causes IBD or disease flares, but we are beginning to understand the complex interactions that exist between the human genes, the environment, normal and abnormal microbial flora, and the immune response in the gut. We are still far away from a unifying theory of IBD, and therefore a treatment that might provide a cure. Until then, we have good medications that can treat the disease and keep it in remission as long as people stay on them and new medications are constantly being developed, some with very promising results. So, stay tuned, there is a fair amount of light at the end of the IBD tunnel.

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Michael Chiorean, MD, is a gastroenterologist with the Digestive Disease Institute at Virginia Mason. He specializes in inflammatory bowel disease, Crohn’s disease, ulcerative colitis, C Difficile, gastrointestinal bleeding and small bowel endoscopy.

Why is Inflammatory Bowel Disease on the Rise?

By Michael Chiorean, MD **

There are more than 1 million people affected with inflammatory bowel disease (IBD) in the United States — about equally distributed between ulcerative colitis and Crohn’s disease. However, the IBD “map” has changed substantially in the last half century throughout the world. Virtually every recent study showed the frequency of these poorly understood disorders has increased, in some cases more than fivefold since the 1950s. And while there is still a fairly strong East-West gradient, developing countries such as India, China and South Korea, where IBD was almost unheard of 30 years ago, have seen a dramatic acceleration of new cases (incidence) that is now paralleling the incidence in the Western world. In fact, it is expected if the current trend continues, most new cases, and the highest disease burden in the world, will be in countries from the Eastern Hemisphere.

MC900434854This phenomenon has puzzled scientists who have studied these disorders for a long time and, so far, an explanation has remained elusive. Most scientists believe IBD is the result of the interplay between the environment, diet, certain medications, genetic variables and an overreactive immune response against normal bacteria in the gut. If all these “planets” align the right way, an individual who may have a genetic predisposition will develop IBD.

Alternative Theories

King Alfred by Founder of Oriel College, after a painting in the Bodleian Library (colour engraving) by English School (19th century) (bridgemanartondemand.com) [Public domain], via Wikimedia Commons

Scientists were not the only ones who tried to provide answers to this enigma. Several unfounded theories have gained some popularity in the general public, in large part by means of social media, and for perhaps no other reason than the fact that they are more fanciful and sometimes sensational in comparison to scientific concepts. Such theories include the intoxication theory (aluminum, artificial sweeteners, food dyes and preservatives are among the most favorite culprits) or even some religious or spiritual theories. For instance, King Alfred of England suffered from an ailment causing pain and “embarrassment” after eating, beginning in his early 20s. He carried his suffering for most of his life. At the time, this was thought to be due to witchcraft, as a punishment for the king’s notorious infidelity. In reality, he was probably suffering from Crohn’s disease.

The Hygiene Hypothesis

The “hygiene hypothesis” suggests our hypersanitary lifestyle is what predisposes genetically prone individuals to develop IBD or other autoimmune or allergic disorders, such as diabetes, rheumatoid arthritis, lupus and asthma. Countries with a higher frequency of infections and parasites have a lower frequency of IBD and vice versa. 

  • Parasites
    In one study from Africa, offspring of women treated for parasites during pregnancy had twice the rate of asthma and allergic disorders compared to children from women who were not treated. Some parasites have developed ways to tame the immune system in the gut in such a way as to become stealthy and induce what we call immune tolerance. Thus, they are able to maintain a relatively peaceful residence in the intestine, where they feed by “stealing” some of the available nutrients. Since we likely coexisted with parasites for millennia, it is possible that people with stronger gut immune systems were able to get rid of parasites faster, gaining a nutritional advantage over their peers when food was scarce and malnutrition was rampant. As intestinal parasites have almost disappeared from most developed countries, the immune system in some individuals may be looking for an alternative target and may find an acceptable “sparring partner” in the normal bowel flora, resulting in progressive inflammation. Normal people are “tolerant” to intestinal microbiota, while subjects with IBD may lose such tolerance and become immunologically overreactive. The bowel may well be an innocent bystander in this process, but it suffers substantial collateral damage resulting in what is usually a self-perpetuating, chronic disease. IBD patients who were administered a species of relatively harmless parasites (pig whipworm) in a few clinical studies, had improvement in their IBD activity, at least short term.
  • Bacteria
    The seemingly endless supply of sanitary and cleansing products, which eliminate 99.99 percent of bacteria and help rid us of serious foodborne illnesses, have probably altered the nature and diversity of friendly bacteria that have colonized our collective bowels for thousands of years. These friendly bacteria were our first line of defense against noxious organisms at a time when antibiotics and vaccines were not available. Consequently, our gain in some infectious diseases may translate in a loss as far as autoimmune disorders.
  • “Early Life Immunological Education”
    While the hygiene hypothesis has not been proven beyond reasonable doubt, it helps explain certain IBD features. For instance, IBD tends to be less common among children with multiple siblings or those who attended day care and undoubtedly share extensive “bug repertoires” with their peers in childhood. (As a side, IBD seems to be also less frequent in children born through vaginal delivery and are breast-fed.) In contrast, IBD is more frequent among children who received multiple antibiotics. While this is by no means cause and effect, the association is at least interesting, if not mesmerizing. This suggests the immune “education” that occurs early in life through exposure to a variety of bugs has long-lasting consequences for a healthy and balanced immune system. So the old adage of letting your children “eat dirt” may have a seed of truth in it and a very important one in IBD.

It is worth mentioning here that vaccines have not been associated with IBD. In fact, they have a very important role in protecting all individuals, including those with IBD and particularly those who are on immunosuppressive drugs against serious infections.

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Michael Chiorean, MD, is a gastroenterologist with the Digestive Disease Institute at Virginia Mason. He specializes in inflammatory bowel disease, Crohn’s disease, ulcerative colitis, C Difficile, gastrointestinal bleeding and small bowel endoscopy.