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In the absence of clear structural or biochemical abnormalities to provide a consistent explanation for its pathophysiology, irritable bowel syndrome (IBS) has been characterized as a functional disease, whose variable presentation includes abdominal pain, bloating, and altered bowel function. IBS is frequently associated with a history of depression, anxiety, or trauma, including childhood abuse, suggesting a brain-gut connection. But other etiologies, such as changes in gut flora from exposure to infection or certain medications, are also supported from clinical studies.¹

Although it鈥檚 important to consider the possibility that the symptoms of IBS have more than 1 etiology, there has been growing interest in the potential for a role played by gut dysbiosis.² (There鈥檚 a variety of evidence to suggest that disturbances in the gut microflora are an isolated or contributing factor in at least some cases of IBS.) This includes a recent study that identified an intestinal microbiotic signature that correlated with severity of IBS.³ In addition, benefits have been attributed to therapies that affect the gut microbiome, including diet, antibiotics, antidepressants, and probiotics.¹

Transplantation shows a benefit

Based on the hypothesis that gut dysbiosis is a cause of IBS, Johnsen and colleagues conducted a randomized trial with fecal microbiota transplantation (FMT), which has been used successfully in the treatment of recurrent Clostridium difficile infection. Characterized as the first randomized, double-blind, placebo-controlled trial of FMT in IBS, the trial enrolled 90 patients with moderate-to-severe IBS based on a score of 鈮�175 on the validated IBS Severity Scoring System (IBS-SSS). Patients with constipation-dominant IBS were excluded, but diarrhea-predominant or mixed diarrhea/constipation IBS was permitted.²

Patients were randomized 2:1 to FMT or placebo. Due to dropouts or the subsequent identification of microscopic colitis, there were 55 patients in the FMT group and 28 patients in the placebo group available for a modified intention-to-treat analysis at the end of 3 months. The primary endpoint was a >75-point reduction in the IBS Severity Scoring System (IBS-SSS) score. An analysis at 12 months was also conducted.²

The results? The primary efficacy endpoint was achieved by 65% of the patients randomized to FMT versus 43% (P=.049) of those randomized to placebo. When compared at 12 months, the difference between FMT (56% response rate) and placebo (36%) was not statistically significant (P=.075).²

A deeper dive into the data

Numerous variables were evaluated in post-hoc analyses. For example, half of the patients in the FMT group received freshly prepared FMT and half received frozen FMT, which wasn鈥檛 administered in a randomized fashion. Nevertheless, after adjustment for functional comorbidities, both types of FMT formulation were judged to have a similar effect on IBS-SSS scores. A second post-hoc analysis suggested that improvement in IBS-SSS score was primarily driven by reductions in pain and bloating, as well as improvement in bowel habits.²

There were no side effects attributed to FMT, but 1 case of vertigo and nausea was attributed to the medication and instrumentation used during the colonoscopy required for FMT.²

One limitation of this trial, acknowledged by lead author Peter H. Johnsen, MD, of the University Hospital of North Norway, Harstad, Norway, was that no microbiota analysis after transplantation was performed due to lack of funding. As a result, 鈥淸we] cannot associate engraftment of the transplant directly to symptom improvement,鈥� Dr. Johnsen reported.

Another acknowledged weakness of this study was the use of the IBS-SSS to define benefit. In the U.S., the Food and Drug Administration has recommended specific endpoints鈥攁bdominal pain intensity and stool frequency鈥攖o be used to judge the efficacy of IBS drug treatments, which differed from the endpoints used in this study.⁴

More FMT studies are planned

Although this is the first randomized and published study of FMT in IBS, numerous nonrandomized studies and case reports have been presented previously at scientific conferences, according to a review of 9 of these publications.⁵ The authors of the review (conducted before the Johnsen trial was published) concluded that the data weren鈥檛 sufficient to draw conclusions about efficacy of FMT for IBS. The authors noted that 8 FMT and IBS studies were registered on ClinicalTrials.gov as of March 2017. The primary goal of most of these studies is to define the efficacy of FMT for IBS. Secondary goals include research into possible bacterial etiology underlying IBS. A better understanding of the bacterial etiology might further inform the goals of treatment.

Published: January 30, 2018