Why Hasn't a Cure Been Found for Crohn's Disease or Ulcerative Colitis?

By Dr. Nancy Fu

When people talk about a Crohn’s disease cure or an ulcerative colitis cure, they are typically implying that they want a medication, surgical procedure, lifestyle change, or a combination of these, that will permanently end the symptoms and progression of the disease. (What is Crohn’s disease? What is ulcerative colitis?) But, despite some remarkable improvements in recent years in the medical treatment of the diseases, there is still no definitive therapy that can be considered a cure for Crohn's disease or ulcerative colitis. Only for ulcerative colitis there is a radical surgical cure, called a proctocolectomy, which involves the surgical removal of the colon and rectum. But a medicinal cure has yet to be found.

Inflammatory bowel disease (IBD) is complicated

Though researchers have made significant strides in understanding how to treat various issues associated with Crohn's and colitis (IBD), the exact causes of IBD aren’t known. In fact, based upon the most recent findings, it appears that inflammatory bowel disease is not one disease but possibly many because it manifests so differently in different individuals.

In Crohn’s disease, the type and severity of symptoms, the location of the inflammation in the gastrointestinal tract and the response to treatment all vary from person to person. There are five types of Crohn’s disease and each type affects a different area of the gastrointestinal tract. Even the progression of Crohn’s disease varies from person to person. Any combination of inflammation, strictures or a narrowing of the intestine, or the development of abnormal passageways (called fistulas) can occur, which makes individualized treatment necessary but challenging.

Ulcerative colitis also manifests differently in each person. The symptoms differ depending on which of the four types of ulcerative colitis you have and where the inflammation is specifically located. Some people have symptoms that come and go with long periods between flare-ups. Others have frequent flare-ups. As with Crohn’s disease, because there is so much variance between the symptoms and progression of ulcerative colitis, each approach to treatment must be individualized.

Ongoing research is revealing that there are many pathways in the body that promote inflammation. For example, tumor necrosis factor (TNF) was once thought to be the sole pro-inflammatory compound associated with Crohn's disease and ulcerative colitis. When anti-TNF therapy was introduced to address TNF several years ago, it was expected that anti-TNFs would revolutionize treatment of the disease. Though it has made a significant difference in the lives of many, anti-TNFs are only effective in about 30% of cases. This implies that there are other pathways promoting inflammation and by understanding these pathways, effective treatments can be developed.

Therefore, many healthcare professionals treating inflammatory bowel disease now view it as a spectrum of diseases and are rethinking how they use terms like “remission.” Genetic and environmental factors are two major players that interact with each other and shape the overall “phenotype” or presentation along the spectrum of inflammatory bowel disease.

Genetic factors

Research evidence supports a genetic component contributing to the development and progression of inflammatory bowel disease (IBD). We see a higher incidence of IBD in people with a history of the disease in their family, especially among first-degree relatives, as compared to those who do not have a similar history. This suggests a genetic predisposition in the development of IBD that may be passed from one generation to the next.
In addition, over one hundred genes have been found to be associated with IBD. For example, NOD2 gene variation is more prevalent in people with Crohn’s disease. As for ulcerative colitis, the genetic association of the disease with one particular gene is not as strong as for Crohn’s, though there are many genes suspected to play a part in both Crohn’s disease and ulcerative colitis. Therefore, genes alone do not adequately explain how IBD occurs and progresses. This leads researchers to investigate the interplay between a person’s genetic predisposition and their environment for greater insight into the cause(s) of IBD.

Environmental factors

Current thinking is that environmental factors appear to play an important and key role in the development of Crohn's disease or ulcerative colitis. Of particular interest is the intestinal microflora or the microorganisms in the intestine. New advances in DNA sequencing are leading researchers to see an important relationship between intestinal microbes and immune function as it pertains to the development of the disease.

Delicate interactions between intestinal microbes and our intestinal mucosal layers are crucial in maintaining a balanced immune system. The exact interactions are currently of great scientific interests. Researchers are working hard to identify the microbes that contribute to optimal intestinal health. People with Crohn's disease or ulcerative colitis have been shown to have “leaky” intestinal mucosa leading to overwhelming interactions of intestinal microbes and their immune system. Finding a way to reset the balance can be an important step toward finding a cure for Crohn's disease or ulcerative colitis.

Cigarette smoking is also a known environmental factor that can significantly alter the intestinal microbial composition. Smoking worsens and accelerates progression of Crohn’s disease but, on the other hand, smokers with ulcerative colitis tend to have fewer and less disease flares. This phenomenon further highlights how environmental factors affect inflammatory bowel disease. (Learn more about the research on smoking and ulcerative colitis as well as smoking and Crohn's disease.)

These links between the genetic and environmental factors with inflammatory bowel disease (Crohn's and colitis) need additional research before we can say with confidence that they point to probable causes. Despite the advances in Crohn's and colitis treatments, there are still many more questions that need to be answered before we can confidently state the exact causes and develop the cure for Crohn's disease and ulcerative colitis. Some of the questions include:
• What causes a failure in the immune system making it attack itself?
• What factors trigger flares or prompt remission?
• How does the microbiota influence immune regulation?
• Why is inflammatory bowel disease unevenly distributed in the gut?

Environmental Risk Factors and the Global Increase of Crohn's Disease and Ulcerative Colitis

So, the development of inflammatory bowel disease involves many factors. Researchers are making progress in identifying the key components and unraveling the complex interactions. In the meantime, people with IBD must focus their efforts toward what we know about effective treatment, control and management of IBD symptoms.

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