Investigating Fecal Microbiota Transplantation as a Treatment for Irritable Bowel Syndrome

Irritable Bowel Syndrome (IBS) is a chronic gastrointestinal disorder that can be associated with daily, debilitating symptoms for patients. Studies suggest that it affects 7-16% of the United States population and 10-15% of the worldwide population, which is predominantly younger people and women (1). Patients suffer from a variety of symptoms that can have a significant impact on their quality of life, including chronic or recurrent abdominal pain, bloating, and stool irregularity. IBS is currently categorized by stool pattern into 4 subtypes: constipation, diarrhea, an alternating pattern of both, or undifferentiated.

IBS is not characterized by any physical, structural, infectious, or metabolic changes in patients. The condition is instead defined as a disorder of bowel function, with atypical motility, and sensation. While IBS was initially considered psychosomatic in nature, recent research has identified objective pathophysiology, in which the gut microbiome appears as a key player.

The microbiome of IBS patients is distinct from healthy patients in its lack of microbial diversity, with specific reduction in the populations of Enterobacteriaceae, Methanobacteriales, lactobacilli, bifidobacteria, and prevotella. We have also observed an increase in the numbers of facultative Klebsiella species and enterococci. Researchers have even noted differences between the gut flora of patients with different subtypes of IBS. Interestingly, a large percentage of IBS patients report that their symptoms began after an episode of gastroenteritis (in particular after infection with Campylobacter, Salmonella, and Shigella), suggesting that the microbiome plays a role in the earliest stages of disease.

Dr.Lembo is currently investigating the role of fecal microbiota transplantation (FMT) in the treatment of IBS. FMT is a procedure in which the gut microflora of a healthy individual is transferred into the colon of a patient. This procedure has proven to be highly effective in treating recurrent C. difficile infection, and is under investigation as a potential therapeutic intervention for several diseases. Dr.Lembo’s study is a randomized controlled trial with 4 different treatment arms. Patients will either be pre-treated with antibiotics or no antibiotics, and subsequently receive FMT from OpenBiome’s healthy donor stool bank or placebo.

CMIT will collect stool samples throughout the study and analyze the gut microbiome composition of all participants before and after FMT, along with the donor stool material. We will use this data to determine the donor strains that successfully colonize the recipient gut, and also analyze the influence of antibiotic pretreatment (intended to remove the patient’s pre-existing microbiome). The objective is to determine the potential of FMT as a therapy for IBS, as well as inform the design of future studies targeting methods to engineer more effect FMT interventions.

Ford AC, Lacy BE, Talley NJ 2017. N Engl J Med;376:2566-78.