By Allison Dostal, PhD
Gastrointestinal problems are one of the most common unpleasant issues that we all experience at some time or another. But what if your upset stomach wasn’t just a passing discomfort? What if severe abdominal pain, cramping, fatigue, and diarrhea became more of your norm and less of a passing annoyance? For more than 1.4 million Americans, these symptoms typify their experience with inflammatory bowel disease (IBD), a disorder characterized by chronic inflammation of the gastrointestinal (GI) tract. The specific cause (or causes) of IBD remain unknown, but one leading hypothesis is that the bacteria that inhabit our GI system – termed the gut microbiome – play a central role. In this post, we’ll take a closer look at this condition and highlight research aimed at elucidating the impact of the microbiome in IBD development, progression, and treatment.
Characteristics, Diagnosis, and Treatment of IBD
Inflammatory bowel disease is unique in that its symptoms vary from person to person, and an individual’s own experience with their condition can differ markedly from another affected person. Most people are diagnosed with one of the two most common types of IBD, which are ulcerative colitis (UC) and Crohn’s disease (CD). The primary distinguishing factor between the subtypes is that in UC, symptoms are limited to the colon. In contrast, any part of the GI tract – from the mouth to the anus – can be affected in CD. In addition, UC only involves the innermost layer of the colon, while CD can extend deeper into the cell layers of the GI tract. Lastly, in CD, the inflammation can “skip”, leaving normal areas between patches of affected GI tract.
Making a clear IBD diagnosis isn’t always as easy as meeting – or not meeting – these criteria. There is no gold standard available for a clear-cut diagnosis, and 5-15% of cases do not meet strict criteria for either UC or CD. These patients fall into the “IBD type unclassified” (IBDU) group. And in up to 14% of patients, the diagnosis changes over time. Despite the difficulty in specific diagnosis, all subtypes of IBD have one strong feature in common: an abnormal response by the body’s immune system. The immune system is composed of various cells and proteins that usually protect our bodies from infection. However, in people suffering from IBD, the immune system reacts inappropriately, and mistakes benign or beneficial cells and bacteria for harmful foreign substances. When this happens, the immune system produces an inflammatory response within the GI tract and produces the symptoms of IBD. This adverse reaction is termed a “flare”, and can result in symptoms such as abdominal pain and cramping, diarrhea, fever, and blood in the stool. People with IBD often have deficiencies in vitamins, minerals and macronutrients stemming from loss of appetite, reduced food intake, and malabsorption from the GI tract. The lack of nutrients can lead to worsening of symptoms or development of new complications.
Treatment for IBD is centered around two goals: achievement of remission and prevention of flares. Anti-inflammatory drugs such as aminosalicylates and antibiotics are often the first line of treatment, and can be followed by corticosteroids, immunomodulators, and/or biologic agents. In severe cases, removal of the affected part of the GI tract is needed if a patient is not responsive to other treatments.
The Role of the Microbiome in IBD
In recent years, it has become clear that the microbes in our gut have a key role in IBD, but the bacteria involved and their associated functions remain largely unknown. An imbalance of the normal gut bactera due to loss or overabundance of certain species is important in the persistence of the inflammatory responses seen in IBD. The role of the gut microbiota in IBD pathogenesis has been demonstrated by studies showing that antibiotic use can reduce or prevent inflammation – antibiotics work by reducing the number and types of bacteria found in the gut, therefore killing microbes that are causing IBD symptoms. Also, results from studies with UC patients who underwent a transfer of stool collected from healthy donors – called a fecal microbiota transplant – had notable disease remission. However, results have not been consistent between studies, due to differences in populations studied, official diagnosis, treatment methods and doses, and methods of assessing study endpoints. Therefore, no consensus on the microbiome’s relationship to IBD has been reached.
As you can imagine, the combination of unpleasant, potentially severe symptoms and an uncertain diagnosis or treatment can result in significant stress on IBD sufferers, their caregivers, and health care providers. The scientific efforts dedicated to identifying causes and cures for IBD have rapidly expanded in recent years due to advances in technology that allow researchers to work toward refining a clear diagnosis, map specific gut bacteria associated with disease development and symptoms, and identify defined targets for therapy. One of these initiatives is the Crohn’s and Colitis Foundation of America (CCFA) Microbiome Initiative, which is dedicated to understanding the role of the gut microbes in IBD, IBD families, and disease flares. Thus far, there are 7 active projects and 30 published manuscripts stemming from the Initiative, which have determined that different subsets of IBD are characterized by signature bacterial compositions and that people carrying different IBD genes have different microbiome compositions, among other accomplishments.
Other organizations are also supporting IBD research endeavors, including the Kenneth Rainin Foundation, whose Innovator Awards program provides $100,000 grants for one-year research projects conducted at non-profit research institutions, and the NIH’s Human Microbiome Project, which has funded several projects aimed at genetic and metabolomic elucidation of risk for Crohn’s disease. Several randomized trials are ongoing at this time, and their results will inform future directions for diagnosis, treatment, and eventual resolution of IBD.
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