用纯肠内营养治疗活动性克罗恩病会降低粪便微生物产物的免疫刺激潜力

IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Caroline Kerbiriou, Caitlin Dickson, Ben Nichols, Michael Logan, Anna Mascellani, Jaroslav Havlik, Richard K Russell, Richard Hansen, Simon Milling, Konstantinos Gerasimidis
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引用次数: 0

摘要

背景:纯肠内营养(EEN)是治疗活动性克罗恩病(CD)的有效方法。本研究探讨了无细胞粪便滤液的免疫刺激潜力,并将其与接受 EEN 治疗的活动性克罗恩病患儿粪便微生物群和代谢物的变化联系起来:方法:在EEN治疗前、治疗中和治疗结束时,用CD患儿的无细胞粪便浆液刺激外周血单核细胞,测量其肿瘤坏死因子α(TNFα)的产生情况。使用质子核磁共振对所使用粪便的代谢组学特征进行了量化,并使用 16S 核糖体 RNA 测序对其微生物群组成进行了量化:11名患者中,有8名(72%)在接受EEN治疗后,粪便钙蛋白(FC)下降幅度大于50%,随后被标记为FC应答者。在这一亚组中,EEN治疗期间外周血单核细胞产生的TNFα减少(P = .008),达到了与健康对照组相同的水平。在发生这些变化的同时,FC应答者粪便中乙酸盐、丁酸盐、丙酸盐、胆碱和尿嘧啶的浓度显著降低,而对甲酚的浓度显著升高。在 EEN 结束时,外周血单核细胞 TNFα 的产生与丁酸盐呈正相关(rho = 0.70;P = .016)。微生物群结构(β多样性)受到 EEN 治疗的影响,在粪便热保护蛋白应答者中,共有 28 个微生物类群发生了显著变化。在 EEN 完成时,TNFα 的产生与 Lachnospiraceae_UCG-004 和 Faecalibacterium prausnitzii 的纤维发酵剂丰度呈正相关,与 Hungatella 和 Eisenbergiella tayi 呈负相关:本研究提供的概念验证数据表明,EEN 的疗效可能来自于对依赖饮食的微生物及其产物的调节,而这些微生物及其产物会导致 CD 患者的炎症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Treatment of Active Crohn's Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products.

Background: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN.

Methods: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing.

Results: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi.

Conclusions: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.

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来源期刊
Inflammatory Bowel Diseases
Inflammatory Bowel Diseases 医学-胃肠肝病学
CiteScore
9.70
自引率
6.10%
发文量
462
审稿时长
1 months
期刊介绍: Inflammatory Bowel Diseases® supports the mission of the Crohn''s & Colitis Foundation by bringing the most impactful and cutting edge clinical topics and research findings related to inflammatory bowel diseases to clinicians and researchers working in IBD and related fields. The Journal is committed to publishing on innovative topics that influence the future of clinical care, treatment, and research.
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