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Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn's disease.

ABSTRACT: A nutritional intervention, exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn's disease (CD). We characterized changes in the fecal microbiota and metabolome to identify the mechanism of EEN. Feces of 43 children were collected prior, during and after EEN. Microbiota and metabolites were analyzed by 16S rRNA gene amplicon sequencing and NMR. Selected metabolites were evaluated in relevant model systems. Microbiota and metabolome of patients with CD and controls were different at all time points. Amino acids, primary bile salts, trimethylamine and cadaverine were elevated in patients with CD. Microbiota and metabolome differed between responders and non-responders prior to EEN. EEN decreased microbiota diversity and reduced amino acids, trimethylamine and cadaverine towards control levels. Patients with CD had reduced microbial metabolism of bile acids that partially normalized during EEN. Trimethylamine and cadaverine inhibited intestinal cell growth. TMA and cadaverine inhibited LPS-stimulated TNF-alpha and IL-6 secretion by primary human monocytes. A diet rich in free amino acids worsened inflammation in the DSS model of intestinal inflammation. Trimethylamine, cadaverine, bile salts and amino acids could play a role in the mechanism by which EEN induces remission. Prior to EEN, microbiota and metabolome are different between responders and non-responders.

SUBMITTER: Diederen K

PROVIDER: S-EPMC7609694 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn's disease.

Diederen Kay K Li Jia V JV Donachie Gillian E GE de Meij Tim G TG de Waart Dirk R DR Hakvoort Theodorus B M TBM Kindermann Angelika A Wagner Josef J Auyeung Victoria V Te Velde Anje A AA Heinsbroek Sigrid E M SEM Benninga Marc A MA Kinross James J Walker Alan W AW de Jonge Wouter J WJ Seppen Jurgen J

Scientific reports 20201103 1

A nutritional intervention, exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn's disease (CD). We characterized changes in the fecal microbiota and metabolome to identify the mechanism of EEN. Feces of 43 children were collected prior, during and after EEN. Microbiota and metabolites were analyzed by 16S rRNA gene amplicon sequencing and NMR. Selected metabolites were evaluated in relevant model systems. Microbiota and metabolome of patients with CD and contr ...[more]

PMID: 33144591

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Project description:BackgroundAlthough there are many hypotheses, the pathogenesis of Crohn's disease (CD) is not completely clear so far. Exclusive enteral nutrition (EEN) is a routine measure in the treatment of active CD. We aimed at investigating the impact of EEN on patients with active CD from microbial metabolomics.Methods16S-rDNA sequencing technology and gas chromatography-mass spectrometer analysis were employed to investigate the modification of the intestinal flora and fecal short-chain fatty acid (SCFA) during the EEN.ResultsSeven patients with CD, who conducted EEN, were followed up successfully in the present study. The 8-week EEN resulted in a remission of the condition of subjects with active CD, as revealed by a significant decrease in erythrocyte sedimentation rate (ESR) (P = 0.018), C-reactive protein (CRP) (P = 0.028), and Crohn's disease activity index (CDAI) (P = 0.018). The nutrition of the subjects was improved after an 8-week treatment course with EEN, which was associated with an increase in body mess index (BMI) (P = 0.018) and serum albumin (ALB) (P = 0.018) levels. Furthermore, our investigations revealed a significantly increased abundance of Firmicutes paralleled by decreased levels of Proteobacteria. With respect to the genus, five species of bacteria including Ruminococcus (P = 0.01), Lachnospiraceae (P = 0.02), Anaerotruncus (P = 0.04), Flavonifractor (P = 0.04), and Novosphingobium (P = 0.05) showed significantly increased abundance. This was accompanied by relative changes in fecal short-chain fatty acids levels. Moreover, we successfully constructed a stable model by combining these five significantly different genera to predict the therapeutic effect of EEN on patients with CD (AUC = 0.9598).ConclusionsThe findings indicated that EEN can alleviate the condition and the nutrition of patients with active CD by regulating the intestinal flora and influencing the expression level of fecal short-chain fatty acids.

Dataset Information

Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn's disease.

Publications

Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn's disease.

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