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Understanding the Gastrointestinal System

Q&A with Dr. William Sandborn on Inflammatory Bowel Disease

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It’s estimated roughly 100 trillion microorganisms reside within our intestines, about 10 times more than the total number of human cells comprising our bodies. By and large, we share space amicably. It’s a mutually agreeable and biologically necessary relationship. Beneficial gut flora help us digest foods, train the immune system, produce vitamins and prevent pathogenic microbes from taking root.

Sometimes, though, things go wrong, resulting in conditions like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). More than 1 million Americans are affected. We asked Dr. William J. Sandborn, chief of the Division of Gastroenterology at the UC San Diego School of Medicine and director of the UC San Diego Health System’s IBD Center to explore the issues.

Q: Does medical science have a pretty good understanding now of how a healthy intestinal system works or, more specifically, what causes a problem like inflammatory bowel disease?

A: I am always hesitant to say that we have a complete understanding, but we do know more than we used to. Advances include evolving understanding of the genetic associations for inflammatory bowel disease, and the role of the patients’ colon bacterial, which we call ‘the fecal microbiome.’

With regard to genetics, there are now 169 genes that are linked with inflammatory bowel disease. This means that the inflammatory bowel diseases – Crohn’s disease and ulcerative colitis – are complex genetic disorders. Related to the fecal microbiome, we now have an understanding that the bacteria in the colons of patients with IBD are different from healthy people without IBD. Our working definition of the cause of IBD is now that a patient with genetic susceptibility develops an inflammatory response to an altered fecal microbiome. Also, there is likely an important contribution of various environmental triggering events, such as cigarette smoking as a trigger for Crohn’s disease.

Q: What’s the difference between inflammatory bowel disease and irritable bowel syndrome? Can the latter lead to the former?

A: Inflammatory bowel diseases are autoimmune diseases in which the patient’s own immune system attacks their small intestine and/or colon. With a colonoscopy or with CT or MRI scan, there are findings of ulceration and inflammation and the patients often experience rectal bleeding in addition to abdominal pain and diarrhea. Treatments are anti-inflammatory and immune suppression.

Irritable bowel syndrome (IBS) is a non-inflammatory condition of the small intestine and/or colon in which the motility or contractions are altered. Colonoscopy and CT or MRI scans are normal. There are two forms of irritable bowel syndrome, diarrhea predominant IBS (the predominant symptom is diarrhea) and constipation predominant IBD (the predominant symptom is constipation). Treatment is targeted on treated the constipation or diarrhea.

Q: Current treatments for IBD seem to mostly involve suppressing the inflammatory immune response through antibiotics, but the result is often long-term adverse side effects and diminishing effectiveness. Where do you see more promise: In tweaking current approaches or in something new altogether?

A: That is not quite true. Antibiotics don’t reliably work for IBD. We do use the anti-inflammatory drug mesalamine (Asacol, Lialda) for ulcerative colitis and immune suppressive drugs (prednisone, azathioprine, 6-mercaptopurine, methotrexate) and biologic drugs (Remicade, Humira, Cimzia) for ulcerative colitis and Crohn’s disease.

These immune suppressive and biologic medications have some potential for side effects. But that said, for patients with significant clinical symptoms the clinical benefits often outweigh the small risks.

However, we are interested in looking at different treatment strategies such as administering steroids directly into the bowel do reduce side effects (Entocort, Uceris), using herbal remedies such as Andrographis paniculatta, stem cell therapy, more selective biologic therapies that only affect the bowel (vedolizumab), etc.

Q: What are your thoughts about some of the more unusual or exotic treatments being proposed or tested for IBD, such as “helminthic therapy” (imbibing whipworm ova) or using cannabis? Do these have a place in the armamentarium?

A: Helminthic therapy with whipworms is a very interesting idea. The rationale is that whipworms induce a natural immune suppressive response by the patient’s own immune system that could treat their ulcerative colitis or Crohn’s disease. There are now clinical trials underway to test this therapy for both forms of IBD. I think it is a very interesting and potentially promising therapy, but it is still investigational at this point in time.

There is no good quality scientific data about the role of cannabis in patients with IBD. We just don’t know either way whether it is helpful, neutral or harmful. For this reason, I don’t think that patients should rely on cannabis as their primary therapy for IBD.

However, we can remain open-minded as to whether some patients could benefit from cannabis in addition to their standard IBD therapy. While I don’t personally prescribe medical cannabis for IBD, I do have patients who choose to take it, and some of them report benefit.

Q: What’s the connection between IBD and colon cancer? Does the risk vary with the type of IBD?

A: Long-term inflammation of the colon in patients with ulcerative colitis and Crohn’s disease involving the colon is associated with an increased risk of colon cancer. Many patients with Crohn’s disease only have small bowel involvement or small bowel and a limited amount of upper colon (the cecum), and in these patients there is not an increased risk of colon cancer.

For patients with Crohn’s disease, which extensively involves the colon, the increased risk of colon cancer is similar to the risk seen in patients with ulcerative colitis. The colon cancer that occurs in patients with IBD starts as a flat lesions rather than a polyp. This is different from the colon cancer that occurs in the general population, which usually begins as a polyp.

To screen for colon cancer in patients with IBD, we recommend a colonoscopy with extensive biopsies of flat tissue every 1-2 years, beginning about 10 years after diagnosis of IBD.