biostudies-literatureHacker DLeona M and Harry B Helmsley Charitable TrustDeutsche ForschungsgemeinschaftNHLBI NIH HHSNational Research Foundation SingaporeLudwig-Maximilians-Universität München2019-2034.e8https://www.ebi.ac.uk/biostudies/studies/S-EPMC12017801biostudies-literatureUnknown32(11)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 vaCell host & microbeExclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn's disease.PMC12017801SFB 1371R01 HL1608622304-059703953575072847Heetmeyer JHacker DKohler NKleigrewe KList MNie JSmith BJMetwaly APollard KSSchwerd TDe Zen FRiva ALe Thi GNeuhaus KHeimes HHolz HPauling JKMahapatra AMeng CSocas KHaller DManz QSiebert KfalseExclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn's disease.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 va2024-01-01T00:00:00Z2024 Nov2025-07-02T03:04:55.769Z2025-07-02T03:04:55.769ZS-EPMC120178013946133710.1016/j.chom.2024.10.001