Marla Dubinsky, MD
Chief, Pediatric Gastroenterology and Hepatology, and Co-Director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center
Icahn School of Medicine at Mount Sinai
Hope for People with IBD and Those at Risk
Crohn's disease and ulcerative colitis are the two most common forms of IBD, causing severe GI symptoms, such as diarrhea, abdominal pain, and rectal bleeding, that can wreak havoc with everyday life. These symptoms can often be controlled with medication, but many people still cycle through periods of remission and flare-ups. Deep, long-term remission is possible with certain biologic therapies, but since IBD is a chronic condition with no cure, therapy is life-long.
A cure remains elusive because we don't know what causes IBD. However, the recent mapping of the human genome (the complete set of a person's genetic information) has strengthened our grasp of how genes relate to complex immune diseases like IBD. In addition, new knowledge of our digestive system's microbiome (the bacteria and other microscopic organisms living in our gut) has initiated promising research into the role of microbes in IBD. These immense advances have helped us better understand the disease's components, and set the stage for exciting new research that may lead to improved treatments, novel therapies, and perhaps even prevention.
What We Know About IBD
We know IBD can run in families; in fact, researchers have so far discovered 163 genetic variants that are seen more frequently in individuals who have IBD. Similarly, many studies show that the gastrointestinal tracts of people with IBD contain certain similar patterns of bacteria, different than those found in people without IBD. We suspect that dysbiosis--an imbalance of "good" and "bad" bacteria--plays an important role in the development of IBD.
We believe IBD is set off by an environmental trigger that marries the genetic and microbial components together, creating a "perfect storm" that causes our body's immune system to respond abnormally to our own gut flora. While we haven't identified the exact environmental triggers yet, potential suspects include smoking, antibiotic use as a child, and nonsteroidal anti-inflammatory drugs.
Unlocking Microbial Mysteries
A next step toward comprehending IBD will be to investigate the particular role that microbes play: Is it the microbes themselves or the substances they generate (called metabolites) that influence the disease? For example, it would be significant to find that an IBD patient's GI tract is missing a type of bacteria that produces short-chain fatty acids, which are key in controlling inflammation. The role of diet on the microbial profile also is currently under investigation.
Understanding more about microbial involvement in IBD may eventually make it possible to individualize treatments by targeting specific gut flora. For instance, if we identify the specific bacteria an IBD patient needs to produce an anti-inflammatory reaction in the gut, we could implant the missing microbes into that individual's GI tract via a fecal transplant. This type of procedure, in which bacteria from the stool of one person's healthy gut is transferred to another person's unhealthy gut via enema or nasogastric tube, has already proven effective against Clostridium difficile, a potentially deadly infection that causes diarrhea.
Sounds yucky, right? Thankfully, a pill may be just around the corner, as reported in a recent study in the New England Journal of Medicine.
(A note about probiotics, the so-called "good" bacteria marketed to promote GI health: Probiotics do not necessarily help with IBD, because the microbes they contain may not be the specific bacteria an IBD sufferer needs to balance his or her pro- and anti-inflammatory bacteria.)
The Road to Prevention
In addition to driving research and development of new, more effective therapies, the concept of genetic and microbial importance in IBD lays the groundwork for a road to prevention. For instance, say we study a large family of relatives who share at least 50 percent of each other's genes (e.g., parents, children, siblings). Several have IBD, and a few don't. We find the family members with IBD all have a "pro-IBD" bacterial profile, and all but one of the remaining relatives have a different microbial profile not associated with the disease.
One sibling, whom we'll call "Joe," has the same "pro-IBD" profile as his relatives who have IBD, but has not yet shown any clinical symptoms. Because he is genetically susceptible and has the same microbiome as the family members with IBD, there is a strong likelihood that the disease would eventually emerge in Joe, too. Imagine a day when we could intervene before IBD strikes and change Joe's microbial pattern by giving him the specific bacteria or metabolites his gut is lacking, thereby reversing his risk and preventing him from ever getting IBD.
Researchers at such institutions as the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai are working hard to understand the complexities of this disease. There is hope for people with IBD, and there is hope for those who don't have IBD but who are at risk. I am optimistic that research today will lead to breakthroughs in the not-too-distant future that will improve treatments, help keep people in deep remission, and prevent disease altogether in those at risk.