独家肠内营养（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 CD 儿童粪便微生物群和代谢物的变化联系起来。测量了外周血单核细胞产生的肿瘤坏死因子 α (TNFα)在 EEN 之前、期间和完成时，用 CD 儿童的无细胞粪便浆液刺激后。使用质子核磁共振对粪便的代谢组学特征进行定量，并通过 16S 核糖体 RNA 测序对其微生物群组成进行定量。在使用 EEN 治疗后，11 名患者中的 8 名 (72%) 表现出粪便钙卫蛋白 (FC) 减少 >50%，并且随后被标记为 FC 响应者。在该亚组中，EEN 期间外周血单核细胞产生的 TNFα 减少 (P = .008)，并达到与健康对照受试者相似的水平。与这些变化并行的是，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着降低，而对甲酚显着增加。 EEN 完成时，外周血单核细胞产生的 TNFα 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 处理的影响，粪便钙卫蛋白应答者中共有 28 个微生物类群发生显着变化。 EEN 完成时，TNFα 的产生与 Lachnospiraceae_UCG-004 和 Faecalibacter prausnitzii 的纤维发酵菌丰度呈正相关，与 Hungatella 和 Eisenbergiella tayi 呈负相关。这项研究提供了概念验证数据，表明 EEN 的功效可能来自饮食调节引起 CD 患者炎症的依赖微生物及其产物。© 2024 克罗恩氏病

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.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.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.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.© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.