Chair of Nutrition and Immunology, TUM School of Life Sciences, Technische Universität München, 85354 Freising, Germany; TUMCREATE, 1 CREATE way, #10-02 CREATE Tower, Singapore 138602, Singapore.
Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital LMU, 80337 Munich, Germany.
Cell Host Microbe. 2024 Nov 13;32(11):2019-2034.e8. doi: 10.1016/j.chom.2024.10.001. Epub 2024 Oct 25.
Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn's disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.
肠内营养（EEN）是小儿克罗恩病（CD）的一线治疗方法，但保护机制尚不清楚。我们建立了一个前瞻性儿科队列，以描述未经治疗的 CD 患者对 EEN 反应时粪便微生物群的功能和代谢物变化（德国临床试验 DRKS00013306）。综合多组学分析从个体可变微生物组谱中识别出网络聚类，lachnospiraceae 和中链脂肪酸是保护性特征。生物正交非典型氨基酸标记选择性地鉴定了响应中链脂肪酸的细菌种类。宏基因组分析鉴定了对 EEN 的高菌株水平动力学反应。使用肠道恒化培养和微生物群转移到无菌 Il10 缺陷小鼠中，进一步验证了饮食暴露粪便微生物群的功能变化。饮食模型条件诱导个体患者特异性菌株特征，以防止或引起无菌小鼠的炎症性肠病（IBD）样炎症。因此，我们提供的证据表明，EEN 治疗通过时间和个体可变微生物组谱的明确功能变化起作用。
