April 2014 Issue
Emerging IBD Treatments
By Sherry Coleman Collins, MS, RDN, LD
Vol. 16 No. 4 P. 18
Experimental therapies involving the use of parasites and human feces to treat IBD have gleaned mixed results in research studies.
Amanda constantly searched for relief from her unresponsive ulcerative colitis, a type of inflammatory bowel disease (IBD). Bouts of chronic diarrhea, pain, and bleeding left her anemic and caused her to lose lots of weight.
After seeking different opinions from several gastroenterologists on what her treatment course should be, she learned of two experimental treatments: helminth therapy and fecal material transplantation. After much consideration, she enrolled in a clinical study that evaluated ulcerative colitis patients receiving fecal transplantation to help eliminate their debilitating symptoms. She was a good candidate for a fecal material transplant, so she decided to give it a try. After a few weeks, she saw no improvement, so she underwent a second fecal transplant. This time, two days posttreatment, her condition began to improve.
IBD includes ulcerative colitis and Crohn’s disease. Each condition is unique, but both fall under the umbrella of IBD because they have similar symptoms, which may include recurrent diarrhea, pain, and weight loss. Ulcerative colitis causes ulcerations throughout the tissue layers in the colon, while Crohn’s disease may involve patchy ulcerations throughout the gastrointestinal tract. Both conditions may cause poor nutrient absorption and lead to malnutrition and vitamin and mineral deficiencies due to patients’ dietary limitations.
While there are specific criteria for each diagnosis, many variations exist in clinical presentation. Typically, treatments for ulcerative colitis and Crohn’s disease involve symptom management and an attempt to encourage remission with the use of antibiotics and immunosuppressive drugs.
In general, it’s important for dietitians to work with IBD patients to ensure they follow a diet that meets their nutritional needs. RDs who are skilled in assessing a diet history and using elimination diets can help clients identify what foods may be causing symptoms as they work with a health care team to rule out food allergies, sensitivities, and intolerances. Medical nutrition therapy is an essential part of helping IBD patients live healthier lives, yet it may not be enough on its own to cause the disease to go into and remain in remission.
While dietitians don’t perform experimental therapies, it’s still imperative that they learn about emerging treatments that may become available to their clients and patients in the future so they can partner with physicians and researchers seeking to find solutions for those suffering from IBD and other digestive diseases.
Influencing the Immune System
In recent decades, immune-mediated diseases as diverse as asthma, allergies, and IBD have increased in prevalence around the world.1 As many as 1.4 million people in the United States have IBD, according to the Crohn’s and Colitis Foundation of America.2
Experts believe the increased prevalence of IBD comes as a result of people living in cleaner, more healthful environments in which there are better sanitation practices that have reduced the risk of diseases caused by parasites and bacteria—a theory often referred to as the hygiene hypothesis.
According to proponents of the hygiene hypothesis, by reducing exposure to bacteria and parasites, the immune system becomes hyperactive, responding inappropriately to nonhazardous substances, such as food and environmental stimuli, and to various systems in the human body, as is the case in autoimmune disease. According to Stacy A. Kahn, MD, an assistant professor of pediatric gastroenterology at the University of Chicago Medicine, better hygiene and a less varied diet also may have changed the human microbiome, reducing the diversity and amount of bacteria found in the gut of people living in more developed countries.
Based on the hygiene hypothesis, researchers have been led to reintroduce such pathogens to determine whether they can produce an immune system response that would counter some of its hyperactivity. The following is a discussion of two experimental treatments involving the use of parasites and fecal material transplantation in IBD treatment.
One experimental treatment for IBD involves infecting individuals with helminths, or parasitic worms that cause infectious diseases of varying degrees of severity. During treatment, the parasites are delivered orally, intravenously, or cutaneously.
According to a January 2009 study by Weinstock and Elliot, helminths have evolved over 100 million years to live in the intestinal track or other locations in their hosts. These organisms colonized humans almost universally until the early 20th century, and more than 1 billion people, primarily in less developed countries, carry helminths even today.3
According to the study, “Inflammatory bowel disease ... probably results from an inappropriately vigorous immune response to contents of the intestinal lumen. Environmental factors strongly affect the risk for IBD. People living in less developed countries are protected from IBD. The ‘IBD hygiene hypothesis’ states that raising children in extremely hygienic environments negatively affects immune development, which predisposes them to immunological diseases like IBD later in life. Modern day absence of exposure to intestinal helminths appears to be an important environmental factor contributing to development of these illnesses. … Controlled reintroduction of such exposures [ex. helminths] during childhood and perhaps beyond may help reestablish immune balance and lower the risk for immunological diseases.”3
Weinstock, who’s a professor of medicine at Tufts University’s Sackler School of Graduate Biomedical Sciences, says human studies focus on helminth species that colonize the host for a short period of time and then disappear. It seems as though specific helminths provoke a specific immune response, so researchers are searching for helminths that will elicit the desired response, with minimal negative side effects and limited colonization. These parasites have been shown to downregulate the immune system to remain inside their host, potentially reversing the mechanisms by which autoimmune disease causes damage. How this happens isn’t completely understood. Weinstock has found that the risks of helminth therapy appear to be small, and more research is needed.
Limited research has been published on the use of helminths to treat IBD.4 A Cochrane review of this therapy revealed just two randomized controlled trials that have assessed the safety of using helminths in ulcerative colitis and Crohn’s disease; only the ulcerative colitis study assessed efficacy.4 In each trial, few participants achieved remission, but few adverse events occurred.
Participants with ulcerative colitis seemed to experience some positive benefit from the treatment compared with placebo, according to the Disease Activity Index, which measures symptoms such as stool frequency, rectal bleeding, appearance of the colon lining, and physician’s assessment.5 The drawback: These studies were small and had many limitations. The Cochrane reviewers determined that insufficient evidence exists to promote the use of helminths to treat IBD, and additional research is necessary.4
Fecal Material Transplants
Research has shown that fecal material transplants from a healthy donor have produced good results in patients suffering from Clostridium difficile (C diff) infection. C diff is a virulent bacterium that causes bloody diarrhea, severe dehydration, and sometimes death.
In fecal material transplantation, healthy stool is collected from another individual, preferably a family member, who lives in the same home. It’s inserted into the recipient via colonoscopy, enema, or nasogastric tube. In a research review of 317 patients, Gough and colleagues found improvement in 92% of treated C diff cases, with few serious adverse events.6
Less research has been done on fecal transplantation and IBD, yet researchers are optimistic about the opportunities that exist. According to Kahn, the research so far has involved very small studies with mixed results. Because IBD includes “incredibly heterogeneous disease” and studies have utilized different protocols, they aren’t comparable.
Moreover, the safety of fecal material transplants in individuals who don’t have C diff is unknown. The FDA has determined that using stool in this context is a drug because it has a major health impact, Kahn says, adding that patients who are interested in fecal transplantation should seek treatment from qualified medical researchers, since the therapy is experimental and not yet widely available.
In the future, researchers hope they’ll be able to use what’s called bacterial “fingerprinting” to determine what bacteria a patient is missing vs. using a shotgun approach to bacterial replacement. Currently, some researchers are using synthetic stool developed by using 30 highly likely microbes that may work as a “super probiotic” to recolonize the gut with healthy bacteria.
RDs Are Needed
Because helminth therapy and fecal material transplantation remain experimental for IBD, and there are limited studies, with mixed results, dietitians should caution patients about attempting to use these treatments at home. Nutrition professionals should refer patients only to qualified researchers using these experimental therapies.
Kahn believes this research will have huge implications in the field of nutrition, since diet can impact the microbiome. As we learn how the body interacts with bacteria and in what ways these bacteria support or inhibit bodily functions, nutrition will become even more important. “MDs and RDNs are partners in treating disease and improving health,” Kahn says. “I hope that as RDNs become more interested, they also will become involved in research, patient education, and advocacy.”
Being able to guide patients to understand emerging treatments and support the work of researchers, gastroenterologists, and the health care team provides opportunities for the RD to be an integral part of patient care.
— Sherry Coleman Collins, MS, RDN, LD, is an Atlanta-based nutrition consultant, writer, and dietitian in private practice, specializing in food allergies and digestive disorders.
1. Okada H, Kuhn C, Fiellet H, Bach JF. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010:160(1);1-9.
2. About IBD. Crohn’s and Colitis Foundation of America website. http://www.ccfa.org/what-are-crohns-and-colitis/newly-diagnosed/about-ibd.pdf. Accessed February 17, 2014.
3. Weinstock JV, Elliott DE. Helminths and the IBD hygiene hypothesis. Inflamm Bowel Dis. 2009;15(1):128-133.
4. Garg SK, Croft AM, Bager P. Helminth therapy (worms) for induction of remission in inflammatory bowel disease. Cochrane Database Syst Rev. 2014;1:CD009400 doi:10.1002/14651858.CD009400.pub2.
5. Summers RW, Elliott DE, Urban JF, Jr, Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology. 2005:128(4);825-832.
6. Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011:53(10);994-1002.