Inflammatory Bowel Disease (IBD)
Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is marked by chronic, destructive inflammation in the gastrointestinal tract. This can lead to rectal bleeding, diarrhea, nutritional deficiencies, and other serious complications like colorectal cancer. IBD often strikes early in life, with a peak onset in adolescence or young adulthood. Treatment often requires the long-term use of multiple drugs and may require surgery to remove the affected region of the intestine. Over the past several decades, NIDDK-supported research has improved our understanding of IBD and yielded new treatment approaches for patients with this disease.
- In the early 1900s, the mortality rate for IBD was estimated to be up to 60 percent.
- By the mid-20th century, it was known that IBD encompasses two distinct but related entities (Crohn’s disease and ulcerative colitis). This was a major step toward understanding IBD, but the risk factors and key players of the disease, such as genetics and the microbiome, were largely unknown.
- Early treatments (before the 1950s) for IBD were limited to surgical removal of the affected area. For people with ulcerative colitis, this would usually mean removal of the entire colon. For Crohn’s disease, surgery would be limited to smaller affected areas, but it would not necessarily cure the disease.
- In the 1950s, clinicians started prescribing anti-inflammatory drugs such as corticosteroids or aminosalicylates. While these treatments did not cure IBD, they significantly improved its mortality rate. Corticosteroids are fast-acting and powerful enough to suppress flareups (the sudden worsening of symptoms) but cannot be used as a long-term treatment because of potentially serious side-effects. Aminosalicylates are better tolerated, but they may not be effective for people with severe IBD symptoms.
- Over the next several decades, physicians started treating IBD with drugs called immunomodulators that are designed to curtail the body’s immune response. Although they can be an effective treatment for those who do not respond to (or cannot tolerate) corticosteroids or aminosalicylates, immunomodulator-based treatments could produce potentially severe side-effects, including an increased risk of infections.
Today and Tomorrow
Keeping Gut Inflammation in Check
- Numerous biologic drugs have been developed to target specific molecules that play important roles in driving inflammation. Several of these drugs have been approved to treat IBD, providing effective treatment options for patients who do not respond to conventional anti-inflammatory or immunomodulator therapies. Not every person with IBD responds to them, however, and they can also have serious side-effects, including a heightened risk of infections.
- More research into the key drivers of intestinal inflammation will offer new ways to curb inflammation in the gut with potentially less side-effects, creating a future of far better health outcomes for people with IBD.
Personalizing Treatments for IBD
- It is now becoming possible to correlate specific genetic variants and other clinical test results with disease severity and responsiveness to therapies. For example, the NIDDK-sponsored Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT) study recently determined that a combination of clinical, genetic, and immunologic tests can be used to predict response to standard medical therapy for children newly diagnosed with ulcerative colitis.
- Treatment for IBD is moving towards more personalized, and ultimately more effective, approaches that consider the complex interactions among the immune system, genetics, and the environment that are driving development of the disease in any given individual.
The Genetics of IBD
- The NIDDK’s IBD Genetics Consortium (IBDGC) is identifying genetic variants that are associated with IBD. In collaboration with the International IBD Genetics Consortium, of which it is a member, the IBDGC has enrolled thousands of IBD patients and identified more than 250 regions of the human genome that convey risk for the disease. This work has established genetics as a key driver of IBD and is continuing to yield important new insights into the complex and individual nature of the disease.
- Further analysis of these genetic regions will lead to the identification of specific genetic variants that convey risk for IBD. This could offer new targets for therapy for people with IBD.
IBD and the Microbiome
- Research has shown that the gut microbiome is an important player in IBD. NIDDK-supported studies continue to demonstrate that the composition and diversity of the microbiome are significantly different in people with IBD, especially during disease flareups. Researchers are identifying the specific microbes and their byproducts that are associated with IBD, which is helping them understand how the disease develops and what approaches may be effective to treat it.
- Future research will seek to elucidate the specific ways in which components of the microbiome may promote IBD—or protect from the disease. Microbiome analyses in individuals with IBD may one day even help personalize treatment of their disease. This could be accomplished by restoring a health-promoting profile of bacteria in the gut of a person with IBD.
Developing New Approaches to Study IBD
- The NIDDK-supported Intestinal Stem Cell Consortium (ISCC) is developing methods to grow small assemblies of cells in the laboratory that look and behave like a miniature portion of a human intestine. These “mini-intestines” can be generated using adult cells as starting material, suggesting that in the future a patient’s own cells could be used to screen for drugs that would be effective for that individual’s disease.
- Personalized mini-intestines could be invaluable research models to study the genetic roots of IBD and how the intestine heals itself when injured, and they may one day even be implanted to repair or replace areas of the gut that have been damaged by inflammation.