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.
Treatment of active Crohn’s disease with exclusive enteral nutrition diminishes the proinflammatory potential of fecal microbial components, hence suggesting a mechanism of action involving modulation of diet-dependent microbes and their products that cause gut inflammation.
方法:用CD患儿的无细胞粪便浆液刺激外周血单核细胞后,测量肿瘤坏死因子α(TNFα)的产生。之前,during,在EEN完成时。使用质子核磁共振及其微生物群组成用16S核糖体RNA测序对所用粪便的代谢组学谱进行定量。
结果: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应答者。在这个子群中,在EEN期间,外周血单核细胞的TNFα产生减少(P=.008),并达到健康对照受试者的水平。在这些变化的同时,粪便中乙酸盐的浓度,丁酸盐,丙酸盐,胆碱,FC反应者的尿嘧啶显着减少,对甲酚显著增加。在EEN完成时,外周血单个核细胞产生的TNFα与丁酸呈正相关(rho=0.70;P=0.016)。微生物群结构(β多样性)受到EEN处理的影响,在粪便钙卫蛋白应答者中,共有28个微生物类群发生了显着变化。在EEN完成时,TNFα的产生与Lachnoshispileae_UCG-004和prausnitzii的纤维发酵罐的丰度呈正相关,与Hungatella和Eisenbergiellatayi呈负相关。
结论:这项研究提供了概念验证数据,表明EEN的疗效可能是由于饮食依赖性微生物及其产物的调节引起CD患者炎症。
用专有肠内营养治疗活动性克罗恩病降低了粪便微生物成分的促炎潜能,因此,这表明了一种涉及饮食依赖性微生物及其引起肠道炎症的产物的调节的作用机制。