Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China.
Nutrients. 2022 Oct 24;14(21):4463. doi: 10.3390/nu14214463.
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 and 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 and 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.
肠内营养（EEN）可诱导儿童克罗恩病（CD）患者缓解。本研究旨在描述 EEN 对儿科 CD 胆汁酸（BA）代谢的影响，并探讨 EEN 富集 BA 抑制炎症反应的作用。十二名入组的儿科 CD 患者表现出 BA 代谢紊乱，通过 UPLC-TQMS 测定，粪便次级和未结合 BA 水平降低，提示存在 BA 代谢紊乱，而肠道微生物群失调和 BA 代谢细菌减少，包括 和 属，通过 shotgun 宏基因组测序评估。EEN 治疗在八周内诱导这些患者缓解，其中 9 名患者缓解持续超过 48 周。EEN 改善了 BA 代谢紊乱，一些富集的 BA，包括胆酸（HCA）、α-鼠胆酸（αMCA），与 CD 症状严重程度降低呈显著相关。这些 BA 与某些细菌的丰度增加显著相关，包括 和 ，它们表达 3β-羟甾脱氢酶和 5β-还原酶。HCA 可抑制 CD 患者外周血单核细胞（PBMC）中 CD4+T 细胞的 TNF-α产生。此外，HCA 腹腔注射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 修饰可能有助于 EEN 诱导的儿科 CD 缓解。
