Use of Faecal Transplantation with a Novel Diet for Mild to Moderate Active Ulcerative Colitis: The CRAFT UC Randomised Controlled Trial

Abstract

Background We evaluated whether integration of novel diets for donors and patients in addition to fecal transplantation (FT) could increase FT remission rate in refractory ulcerative colitis (UC). Methods This was a blinded randomized controlled trial in adults with active UC, defined by a simple clinical colitis activity index (SCCAI) of ≥5 and ≤ 11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on day 1and rectal enemas on days 2 and 14 without dietary conditioning of the donor. Group 2: FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet (UCED) for the patients. Group 3 received the UCED alone. The primary endpoint was week 8 clinical steroid free remission, defined as SCCAI <3. Results Sixty two of 96 planned patients were enrolled. Remission week 8 Group 1 was 2/17 (11.8%), Group 2 4/19 (21.1%), Group 3 6/15 (40%) (NS). Endoscopic remission was Group 1 2/17 (12%), Group 2 3/19 (16%), Group 3 4/15 (27%) (Group 1 vs.3 p=0.38). Mucosal healing (Mayo 0) was achieved only in Group 3 (3/15, 20%) vs. 0/36 FT patients (p=0.022). Exacerbation of disease occurred in 3/17 (17.6%) Group 1, 4/19 (21.1%) Group 2, and 1/15 (6.7%) Group 3 (Group 2 vs.3, p=0.35). Conclusions UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.

Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial

“…FMT was safe and no serious adverse events were reported. The minor adverse events were similar to that reported by other RCTs 13 30–33…”

“…There are certain other novel findings. The study design was different from previous RCTs, as the comparator arm here was optimisation of medical therapy, rather than a true placebo, while, except for one, previous RCTs have either included placebo or autologous FMT as a comparator arm 13 30–34. This accounted for relatively higher clinical/endoscopic remission and response rates in the comparator arm compared with previous RCTs (which reported positive results with FMT).…”

“…Diet has a potential to enhance the success of FMT by creating a favourable niche for the engraftment of donor microbiota and by its own anti-inflammatory effect 12. However, except for a recent three-arm study which compared FMT and diet, FMT alone and diet alone in patients with refractory UC, there is no study which has evaluated the combination of diet and FMT in UC 13. Moreover, this study had a small sample size with 17, 19 and 15 patients in each arm, respectively.…”

A Novel UC Exclusion Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A Prospective Open-Label Pilot Study

“…Another weakness of the study is that we did not perform colonoscopy in order to evaluate mucosal healing. However, recently, we have published a randomized controlled trial in adult patients with active refractory UC, showing that the UCED alone appeared to achieve mucosal healing versus single-donor fecal transplantation with or without diet, as mucosal healing (Mayo 0) was achieved only in the group that received the UCED (3/15, 20%) vs. 0/36 of the patients who received fecal transplantation (p = 0.022) [51]. However, we emphasize that, without a placebo group, caution needs to be taken in interpreting our results, as some of the response could be mediated by placebo effects.…”

Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance

“…UCED was designed to alter dietary components that may adversely affect goblet cells, mucus permeability, and microbiome composition, which were previously linked to UC. The research team also reported in another study that UCED alone appeared to achieve higher clinical remission and mucosal healing than FMT with or without diet [ 34 ], and a randomized controlled trial is currently investigated. The diet intervention was not included in our study; however, the participants were required to take less saturated fat and food additives during the 8 weeks of follow-up.…”