Exclusive Enteral Nutrition Initiates Protective Microbiome Changes to Induce Remission in Pediatric Crohn’s Disease

Abstract

AbstractExclusive enteral nutrition (EEN) is the first-line therapy for pediatric Crohn’s disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort (n = 1271 fecal samples) to characterize the function of fecal microbiota and metabolite changes of treatment-naïve CD patients in response to EEN. Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, withLachnospiraceaeand medium chain fatty acids as protective features. Metagenomic analysis identified strain-level dynamics in response to EEN cessation, and 577 gene functions with significant changes in abundance. Functional changes of diet-exposed fecal microbiota were further validated in a combined approach using gut chemostat cultures and microbiota transfer into germ-freeIL-10- deficient mice. EEN-like and fiber-rich dietary model conditions respectively prevented or induced 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.