Exclusive Enteral Nutrition Exerts Anti-Inflammatory Effects through Modulating Microbiota, Bile Acid Metabolism, and Immune Activities.

Exclusive Enteral Nutrition Exerts Anti-Inflammatory Effects through Modulating Microbiota, Bile Acid Metabolism, and Immune Activities.
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独家肠内营养通过调节微生物群、胆汁酸代谢和免疫活动发挥抗炎作用

DOI:
10.3390/nu14214463
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发表时间:
2022-10-24
期刊:
影响因子:
5.9
通讯作者:
Zhang, Ting
Zhang, Ting
中科院分区:
医学2区
文献类型:
--
作者:
Xiao, Fangfei;Gao, Xuefeng;Hu, Hui;Le, Jun;Chen, Yongheng;Shu, Xingsheng;Liang, Ziwei;Xu, Yang;Wang, Yizhong;Zhang, Ting

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完全肠内营养(EEN)可使儿童克罗恩病(CD)患者病情缓解。本研究旨在描述EEN对儿童CD胆汁酸代谢的影响,并探讨富含EEN的BA抑制炎症反应的作用。12例入选的儿童CD患者均表现为BA代谢异常,UPLC-TQMS测定的粪便次级和未结合BAs水平降低,并伴有肠道微生物区系失调,鸟枪法测定BA代谢的细菌包括真细菌和瘤胃球菌属。这些患者在治疗后8周出现缓解,其中9例持续稳定缓解超过48周。即使改善了BA的代谢异常,一些浓缩的BA,包括猪胆酸(Hca)、α-鼠李酸(α-Mca),也与CD症状的严重程度减轻密切相关。这些BA与某些细菌的丰度增加显著相关,包括表达3-β-羟基类固醇脱氢酶和5-β-还原酶的无辜梭菌和红曲霉。羟基喜树碱可抑制CD患者外周血单个核细胞产生肿瘤坏死因子α。此外,腹腔注射羟基喜树碱可减轻葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎。我们的数据表明,BA的修饰可能有助于EEN诱导的儿童CD的缓解。
Exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn’s disease (CD). This study aims to depict EEN’s modification of bile acid (BA) metabolism in pediatric CD and explores the effect of the EEN-enriched BA in inhibiting the inflammatory response. The twelve enrolled pediatric CD patients showed BA dysmetabolism, represented by decreased levels of fecal secondary and unconjugated BAs as determined by UPLC–TQMS, which were accompanied by gut microbiota dysbiosis and reduced BA-metabolizing bacteria including Eubacterium and Ruminococcus genera, assessed by shotgun metagenomic sequencing. EEN treatment induced remission in these patients at eight weeks, and nine patients remained in stable remission for longer than 48 weeks. EEN improved BA dysmetabolism, with some enriched BAs, including hyocholic acid (HCA), α-muricholic acid (αMCA), strongly associated with decreased severity of CD symptoms. These BAs were significantly correlated with the increased abundance of certain bacteria, including Clostridium innocuum and Hungatella hathewayi, which express 3β-hydroxysteroid dehydrogenase and 5β-reductase. HCA could suppress TNF-α production by CD4+ T cells in the peripheral blood mononuclear cells (PBMCs) of CD patients. Moreover, intraperitoneal injection of HCA could attenuate dextran sulfate sodium (DSS)-induced mouse colitis. Our data suggests that BA modification may contribute to the EEN-induced remission of pediatric CD.
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