Enteral nutrition promotes the remission of colitis by gut bacteria-mediated histidine biosynthesis

作者：Wanyi Zeng, Jinjie Wu, Hongyu Xie, Haoyang Xu, Dayi Liang, Qilang He, Xiaoya Yang, Chen Liu, Junli Gong, Qiang Zhang, Zhanhao Luo, Yuan Chen, Zhen He, Ping Lan · 发表于：EBioMedicine · 年份：2024 · DOI：10.1016/j.ebiom.2023.104959 · 被引用次数：45 · 研究领域：Gut microbiota and health、Clinical Nutrition and Gastroenterology、Inflammatory Bowel Disease

Background Exclusive enteral nutrition (EEN) is an important alternative strategy for patients with Crohn's disease (CD), and during this process, microbiota alterations have been observed. However, the underlying mechanisms by which EEN reduces intestinal inflammation are currently unclear. Methods The therapeutic potential of enteral nutrition (EN) was assessed using various mouse models. Fecal full-length 16S rDNA sequencing analysis and several CD metagenome datasets were used to identify the candidate therapeutic bacteria Faecalibaculum rodentium ( F. rodentium ). Whole genome sequencing of F. rodentium and widely-targeted metabolome analysis of the supernatant showed that EN-induced F. rodentium accumulation protected against colitis via histidine biosynthesis. Findings The therapeutic potential of EN therapy was observed in both dextran sulfate sodium (DSS)-induced colitis and Il10 −/− spontaneous colitis mouse models. Accumulation of F. rodentium after EN therapy was determined using full-length 16S rDNA sequencing and verified with several metagenome datasets from patients with CD. Colonization of an isolated F. rodentium could reduce colitis in Il10 −/− mice. Significant histidine enrichment was observed in the F. rodentium culture supernatant, and a series of histidine biosynthesis genes were observed in the F. rodentium genome. Engineered Escherichia coli Nissle 1917 (EcN), encoding the heterologous hisG of F. rodentium (EcN-hisG), which was a key driver of histid...