Faecal Transplantation for Ulcerative Colitis From Diet Conditioned Donors Followed by Dietary Intervention Results in Favourable Gut Microbial Profile Compared to Faecal Transplantation Alone.

Haim Leibovitzh, Chen Sarbagili Shabat, Ayal Hirsch, Eran Zittan, Maria Chiara Mentella, Valentina Petito, Nathaniel Aviv Cohen, Yulia Ron, Naomi Fliss Isakov, Jorge Pfeffer, Michal Yaakov, Caterina Fanali, Laura Turchini, Luca Masucci, Gianluca Quaranta, Nitzan Kolonimos, Anastasia Godneva, Adina Weinberger, Franco Scaldaferri, Nitsan Maharshak
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Abstract

Background and aims: Several faecal 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 faecal 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]. Faecal samples were assessed by DNA shotgun metagenomic sequencing.

Results: Following diet conditioning, donors showed depletion in metabolic pathways involved in biosynthesis of sulphur-containing amino acids. Only Group 2 showed significant shifts towards the donors' microbial composition [ADONIS: R2 = 0.15, p = 0.008] and significantly increased Eubacterium_sp_AF228LB post-intervention [β-coefficient 2.66, 95% confidence interval 2.1-3.3, q < 0.05] which was inversely correlated with faecal 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 faecal calprotectin.

Conclusion: FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favourable microbial profiles which correlated with decreased faecal calprotectin. Our findings support further exploration of the additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.

与单独移植粪便相比,从饮食调节供体中移植粪便治疗溃疡性结肠炎,然后进行饮食干预,可获得良好的肠道微生物状况。
背景和目的:针对溃疡性结肠炎(UC)的几种粪便微生物移植(FMT)方法已进行过研究,但结果相互矛盾。我们最近发表了 CRAFT-UC 试验的临床结果,该试验将 FMT 与 UC 排异饮食(UCED)结合使用,并与单独使用 FMT 进行了比较。在此,我们旨在从微生物谱和功能方面对两种 FMT 策略进行比较:方法:CRAFT-UC 研究招募的受试者均提供了干预前和干预后的粪便样本。捐献者根据 UCED 原则接受为期 14 天的饮食调节。第 1 组接受结肠镜检查(第 1 天)和灌肠(第 2 天和第 14 天),不对供体进行饮食调节(N=11)。第二组接受 FMT,但对供体进行饮食预处理,并对患者进行 UCED(10 人)。粪便样本通过 DNA 猎枪元基因组测序进行评估:结果:在进行饮食调节后,供体参与含硫氨基酸生物合成的代谢途径出现衰竭。只有第 2 组的供体微生物组成发生了明显变化(ADONIS:R2=0.15,p=0.008),干预后 Eubacterium_sp_AF228LB 显著增加(β系数 2.66,95%CI 2.1-3.3,q 结论:饮食调节供体的 FMT 在干预后显著增加:从饮食调节供体中摄取 FMT,然后再摄入 UCED,会导致微生物改变,这与粪便钙蛋白减少有关,有利于微生物谱的形成。我们的研究结果支持进一步探索饮食干预对供体和接受 FMT 的患者的额外益处,并将其作为治疗 UC 的一种潜在方法。
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