The Microbiome in IBD: Illuminating the Way to New Treatments

by Kristina C. - November 28, 2016

Photo Credit: by Kristina Campbell
Photo Credit: by Kristina Campbell

A diagnosis of Crohn's or ulcerative colitis means coming to terms with a disease that has no cure. When it comes to these inflammatory bowel diseases (IBDs), several effective treatment options exist—and they have to be woven into a person's everyday life because they must usually continue for the long term.

Doctors want to control the digestive tract inflammation in those with IBD, and they know that not all people respond to the same treatment. Generally, a person with a new IBD diagnosis would try therapies with gradually increasing power: first, one of the 5-aminosalicylate/sulfasalazine drugs, then an immunosuppressant drug like methotrexate (with an option of corticosteroids), and if that fails, a biologic therapy which targets specific proteins that are thought to cause IBD inflammation. If all of these still can’t control the disease activity, then a person might enter clinical trials for investigational drugs, or have digestive tract surgery as a last resort.

Some people progress through these treatment steps without relief of their inflammation, maybe even having to undergo repeated surgeries. Many patients are looking for different treatments to replace or complement the ones in use now. Fortunately, a whole new range of treatments may emerge in the next few years based on a newly identified factor in the pathogenesis of IBD: the gut microbiota — the thriving community of microbes living in the gastrointestinal tract.

Scientists now understand that the gut microbiota plays a role in how inflammatory bowel diseases develop. IBD begins with a genetic predisposition, of course, but recent science shows environmental factors can contribute to an abnormal community of gut microbes (informally called a “dysbiosis”). One anti-inflammatory kind of bacteria, Faecalibacterium prausnitzii (or F. prau for short), is particularly low in the guts of people with IBD.

Digestive tract inflammation can result from this dysbiosis, and then the dysbiosis can help perpetuate the inflammation—the resulting never-ending cycle has been called the 'inflammatory loop'.

Photo Credit: by Kristina Campbell
Photo Credit: by Kristina Campbell

With these new insights about gut bugs and IBD, new treatments are on the horizon. At least three possibilities emerge:

1) Using the gut microbiota to sub-group those with IBD

Right now, it's a given that not everyone will respond the same way to a single IBD drug—say, the corticosteroid medication budesonide (Uceris). But in the future, a person with IBD might be able to test her microbiome before trying out Uceris to predict whether she'll respond to it. That way, the right drugs can be given to the right person, without so much trial and error. For example, with the related inflammatory disease rheumatoid arthritis, a recent study showed that the baseline microbiota predicted who would improve significantly 3 and 6 months into the therapy. This kind of trial could also be done for IBD drugs.

2) Using diet to complement existing therapies

With the scientific study of gut bugs, diet emerges as a possible mainstream treatment, too. To date there's little scientific evidence that changing diet can meaningfully affect IBD disease symptoms, yet many patients claim their diet matters immensely. This discrepancy could exist because the dietary changes that make a difference could depend on the personal mix of microbes in a patient's digestive tract. That is to say, when a certain way of eating—like the low-FODMAP diet — is tested on a population of people with IBD, it works well for some but not for others, so on average it shows very little effect. But if the diet could be tested on a smaller set of people with IBD who have a certain collection of gut bacteria, it might work beautifully for all of them. More studies will help sort this out.

3) Using live bacteria as new therapies

Changing the bacterial mix by putting the right live bacteria into the digestive tract could constitute a new therapy for those with IBD—in other words, "bugs as drugs". First, scientists need to figure out more details about the set of gut bacteria that characterizes Crohn's and ulcerative colitis, and then they can figure out specific cocktails of microbes that could change the gut ecosystem to reduce inflammation.

Fecal microbiota transplantation (FMT) is already a way of using live bacteria therapeutically: the treatment is a pre-existing messy mix from someone else's digestive tract (namely, stool). FMT has shown some promise for treating ulcerative colitis in clinical trials, but it doesn't work dramatically better than existing treatments and researchers need to better characterize the long-term risks of FMT before it can become widespread.

Instead of changing the bugs themselves, therapies could also emerge that successfully change the molecules released by the bacteria in the digestive tract. Because some of the molecules (a.k.a. metabolites) are associated with inflammation, altering them might be able to stop the inflammation.

Companies are working on some of these possibilities, aiming to get these new drugs and therapies to market as soon as they can. New options could soon help IBD patients who are in desperate need of alternatives.


Kristina Campbell is a freelance science writer specializing in the gut microbiota and digestive health.

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