Fecal transplantation for ulcerative colitis from diet conditioned donors followed by dietary intervention results in favorable gut microbial profile compared to fecal transplantation alone.

BACKGROUND AND AIMS: Several fecal microbial transplantation (FMT) approaches for ulcerative colitis (UC) have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT-UC Trial using FMT with the UC Exclusion Diet (UCED), compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function. METHODS: Subjects recruited to the CRAFT-UC study with available pre- and post-intervention fecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group-1 received single FMT by colonoscopy (Day 1) and enemas (Days 2 and 14) without donors' dietary conditioning (N=11). Group-2 received FMT but with donors' dietary pre-conditioning and UCED for the patients (N=10). Fecal samples were assessed by DNA shotgun metagenomic sequencing. RESULTS: Following diet conditioning, donors had depletion in metabolic pathways involved in sulfur-containing amino acids biosynthesis. Only Group-2 showed significant shifts towards the donors' microbial composition (ADONIS: R2=0.15, p=0.008) and significant increased Eubacterium_sp_AF228LB post-intervention (ß-coefficient 2.66, 95%CI 2.1-3.3, q<0.05) which was inversely correlated with fecal calprotectin (rho=-0.52, p=0.035). Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post intervention in Group-2 and were significantly inversely correlated with fecal calprotectin. CONCLUSION: FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favorable microbial profile which correlated with decreased fecal calprotectin. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.

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

BACKGROUND: We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC]. METHODS: This was a blinded, randomised, 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 received 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: Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 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%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of 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.

Preoperative Exclusive Total Parental Nutrition is Associated with Clinical and Laboratory Remission in Severe Active Crohn's Disease-A Pilot Study.

BACKGROUND: The effect of 1-3 months of preoperative exclusive total parental nutrition (TPN) in active Crohn's disease (CD) patients is not well established. We investigated the efficacy of exclusive TPN in active CD patients. METHODS: In a retrospective multi-visit study with data according to our standard care therapy, we assessed clinical and laboratory remission to refractory CD with exclusive preoperative TPN. Inclusion required exclusive preoperative home TPN without additional oral intake for 1-3 months prior to planning surgery. RESULTS: Twenty preoperative CD patients (65% male; 35% female) were on exclusive TPN. The mean age of the cohort was 30.8 ± 11.6 years. Mean duration of preoperative TPN treatment was 73 days (range: 24-142 days). Most patients had terminal ileal (35%) or ileocolonic CD (30%), and with stricturing (B2) phenotype. All 20 patients had significant clinical improvement in all disease activity indices at the end of preoperative TPN (baseline vs. post TPN): HBI 14.5 vs. 4.0 (p = 0.001); BMI 19.2 vs. 19.7 kg/m2 (p = 0.017); CRP 57.2 vs. 10.3 mg/L (p = 0.001); Fecal calprotectin (FC) 672 vs. 200 (µg/g); albumin 2.7 vs. 3.6 g/dL (p = 0.001). Two patients (10%) no longer required surgery after completion of exclusive TPN. CONCLUSION: Exclusive preoperative TPN was found to provide significant improvement in nutritional status, and clinical and laboratory remission in severe active Crohn's patients.