P1203 Fecal transplantation for Ulcerative Colitis from diet conditioned donors followed by dietary intervention results in favorable gut microbial profile and decreased gut inflammation compared to fecal transplantation alone
Authors: Leibovitzh H , Sarbagili Shabat C , Hirsch A , Zittan E , Mentella M C , Petito V , Cohen N A , Ron Y , Fliss Isakov N , Pfeffer J , Yaakov M , Fanali C , Turchini L , Masucci L , Quaranta G , Kolonimos N , Godneva A , Weinberger A , Scaldaferri F , Maharshak N 
Published: January 2024

Abstract

Background
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), a novel diet for active UC, compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and functional outcomes.

Methods
Subjects recruited to the CRAFT UC study with available pre- and post-intervention fecal samples were included. Seven donors received diet conditioning for 14 days in line with the UCED principles. Group 1 received single donor standard FMT by colonoscopy on Day 1 and rectal enemas on Days 2 and 14 without dietary conditioning of the donor (N=11). Group 2 received FMT as above but with dietary pre-conditioning of the donor and UCED for the patients (N=10). Pre- and post-intervention fecal samples were assessed by DNA shotgun metagenomic sequencing to obtain microbial compositional and functional data. Data was analyzed using a multivariable linear regression mixed effects model and spearman correlation. Benjamini-Hochberg correction was used for multiple testing with p-values&lt;0.05 and q-values&lt;0.2 considered significant.

Results
Following diet conditioning, donors had significant depletion in microbial metabolic pathways involved in the biosynthesis of sulfur-containing amino acids. Only patients in Group 2 receiving FMT from diet conditioned donors followed by the UCED showed significant shifts towards the donors’ microbial composition (ADONIS: R2=0.15, p=0.008). Eubacterium sp AF228LB was significantly increased post-intervention in Group 2 (β-coefficient 2.66, 95% CI 2.1 to 3.3) and was also inversely correlated with fecal calprotectin levels (rho=-0.52, p=0.035). Moreover, microbial metabolic pathways involved in gut inflammation and barrier function including ribonucleotides biosynthesis (β-coefficient 0.29, 95% CI 0.07 to 0.51) and branched chain amino acids (β-coefficient 0.44, 95% CI 0.16 to 0.72) were enriched post intervention only in Group 2 and were significantly correlated with decrease in fecal calprotectin (rho=-0.78, p=0.01 and rho=-0.58, p=0.09, respectively).

Conclusion
FMT from diet conditioned donors followed by the UCED diet led to microbial alterations associated with favorable microbial compositional and functional profile related to sulfur metabolic pathways, which translated to decreased gut inflammation. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of active UC.