Fecal Transplantation: Any Real Hope for Inflammatory Bowel Disease?

Paul Moayyedi

Disclosures

Curr Opin Gastroenterol. 2016;32(4):282-286. 

In This Article

Fecal Microbial Transplantation in the Treatment of Ulcerative Colitis

The first description of the use of FMT in ulcerative colitis was a case report from the United Kingdom in 1989.[13] The FMT was given as an enema and the patient was reported to be in remission and symptom free without any medication 6 months later. This was followed by a series of successful case reports of FMT in a variety of gastrointestinal diseases, including ulcerative colitis, from Borody et al.[14] in Sidney, Australia with promising initial results. As FMT became popular in the treatment of antibiotic resistant C. difficile infection others also started using this approach in ulcerative colitis.[15] A systematic review[16] identified 17 citations of case series or case reports in the use of FMT in IBD involving a total of 18 ulcerative colitis patients and reported that most cases were successfully treated. A more recent systematic review[17] focused on case series that met prespecified length of follow-up requirements and identified four papers involving 27 ulcerative colitis patients with a pooled remission rate of 24% [95% confidence interval (CI) = 11–45%].

There are also two randomized controlled trials (RCTs)[18,19] that have compared FMT with placebo in active ulcerative colitis. Moayyedi et al.[18] recruited 75 active ulcerative colitis patients and randomized patients to FMT from an unrelated donor given by enema once per week for 6 weeks or a water enema given at the same volume and frequency. This trial[18] reported a statistically significant benefit with 9/38 (24%; 95% CI = 11–40%) of the FMT group in remission at week 7 compared with 2/37 (5%) in the placebo group. Interestingly, the remission rate and 95% CI in this trial was similar to that reported in the systematic review of case series.[17] Subgroup analysis suggested that FMT may be donor dependent and that remission rates may be higher if FMT is given early in the course of disease as remission occurred in 3/4 (75%) in those that have had ulcerative colitis for a year or less. This was the planned primary subgroup analysis and it is biologically plausible that FMT may be more effective if given before the endogenous microbiome becomes entrenched; however the numbers are too small to draw any definitive conclusions. The picture is further complicated by the second trial by Rossen et al.[19] that randomized 48 patients with active ulcerative colitis to FMT or placebo. Patients were given FMT by nasoduodenal tube at time 0 and 3 weeks from a healthy donor or using autologous fecal microbiota (placebo) and remission was assessed at week 12. There was no statistically significant benefit of FMT with 7/23 (30%) of the active group achieving remission compared with 5/25 (20%) controls.

It is therefore unclear whether FMT is effective in ulcerative colitis given that the RCTs have given conflicting results. However, Rossen et al. was a smaller study and only gave two FMT doses 3 weeks apart via the nasoduodenal route. It is possible that FMT needs to be given more frequently,[20] and may be better given as a retention enema given that ulcerative colitis always involves the rectum so FMT may be more effective if delivered to the site of initial perturbation of the microbiome. It is also possible that the two trials are not contradictory as if the two RCTs are pooled there is a significant effect of FMT at inducing remission in ulcerative colitis with no heterogeneity between studies (Fig. 1). The number needed to treat = 6 (95% CI = 3–33) for the pooled results of the trials (Fig. 1), which compares favourably with other therapies for active ulcerative colitis.[3]

Figure 1

Forest plot of the two placebo controlled randomized trials of fecal microbiota transplant therapy in active ulcerative colitis.

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