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

Kay Diederen; Jia V. Li; Gillian E. Donachie; Tim G. de Meij; Dirk R. de Waart; Theodorus B. M. Hakvoort; Angelika Kindermann; Josef Wagner; Victoria Auyeung; Anje A. te Velde; Sigrid E. M. Heinsbroek; Marc A. Benninga; James Kinross; Alan W. Walker; Wouter J. de Jonge; Jurgen Seppen

doi:10.1038/s41598-020-75306-z

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

Kay Diederen, Jia V. Li, Gillian E. Donachie, Tim G. de Meij, Dirk R. de Waart, Theodorus B. M. Hakvoort, Angelika Kindermann, Josef Wagner, Victoria Auyeung, Anje A. te Velde, Sigrid E. M. Heinsbroek, Marc A. Benninga, James Kinross, Alan W. Walker, Wouter J. de Jonge, Jurgen Seppen^* (Corresponding Author)

^*Corresponding author for this work

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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.

Original language	English
Article number	18879
Pages (from-to)	18879
Number of pages	17
Journal	Scientific Reports
Volume	10
DOIs	https://doi.org/10.1038/s41598-020-75306-z
Publication status	Published - 3 Nov 2020

Bibliographical note

GD and AWW receive core funding support from the Scottish Government’s Rural and Environmental Science and Analytical Services (RESAS) Division. JW was funded by the Wellcome Trust [Grant No. 098051]. JVL is funded by MRC New Investigator Grant (MR/P002536/1) and ERC Starting Grant (715662). JK is funded by NIHR: II-OL-1116-10027, NIH: R01-CA204403-01A1, Horizon H2020: ITN GROWTH. Imperial Biomedical Research Centre, SAGES research grant. Infrastructure support for this research was provided by the NIHR Imperial biomedical Research Centre (BRC). Microbiota analyses were carried out using the Maxwell computer cluster at the University of Aberdeen. We thank the Illumina MiSeq team at the Wellcome Sanger Institute for their assistance. This work was partially described in the Ph.D. thesis of KD (Retrieved 2020, Pediatric inflammatory bowel disease Monitoring, nutrition and surgery, https://pure.uva.nl/ws/files/23176012/Thesis_complete_.pdf).

Keywords

gastronenterology
gastrointestinal diseases
microbiology
DEXTRAN SULFATE SODIUM
INTESTINAL MICROBIOTA
NMR-SPECTROSCOPY
RECEPTOR
TGR5
L-CARNITINE
INFLAMMATORY-BOWEL-DISEASE
COLITIS
CORTICOSTEROIDS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Diederen, K., Li, J. V., Donachie, G. E., de Meij, T. G., de Waart, D. R., Hakvoort, T. B. M., Kindermann, A., Wagner, J., Auyeung, V., te Velde, A. A., Heinsbroek, S. E. M., Benninga, M. A., Kinross, J., Walker, A. W., de Jonge, W. J., & Seppen, J. (2020). Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn’s disease. Scientific Reports, 10, 18879. Article 18879. https://doi.org/10.1038/s41598-020-75306-z

Diederen, K, Li, JV, Donachie, GE, de Meij, TG, de Waart, DR, Hakvoort, TBM, Kindermann, A, Wagner, J, Auyeung, V, te Velde, AA, Heinsbroek, SEM, Benninga, MA, Kinross, J, Walker, AW, de Jonge, WJ & Seppen, J 2020, 'Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn’s disease', Scientific Reports, vol. 10, 18879, pp. 18879. https://doi.org/10.1038/s41598-020-75306-z

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title = "Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn{\textquoteright}s disease",

abstract = "A nutritional intervention, exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn{\textquoteright}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.",

keywords = "gastronenterology, gastrointestinal diseases, microbiology, DEXTRAN SULFATE SODIUM, INTESTINAL MICROBIOTA, NMR-SPECTROSCOPY, RECEPTOR, TGR5, L-CARNITINE, INFLAMMATORY-BOWEL-DISEASE, COLITIS, CORTICOSTEROIDS",

author = "Kay Diederen and Li, {Jia V.} and Donachie, {Gillian E.} and {de Meij}, {Tim G.} and {de Waart}, {Dirk R.} and Hakvoort, {Theodorus B. M.} and Angelika Kindermann and Josef Wagner and Victoria Auyeung and {te Velde}, {Anje A.} and Heinsbroek, {Sigrid E. M.} and Benninga, {Marc A.} and James Kinross and Walker, {Alan W.} and {de Jonge}, {Wouter J.} and Jurgen Seppen",

note = "GD and AWW receive core funding support from the Scottish Government{\textquoteright}s Rural and Environmental Science and Analytical Services (RESAS) Division. JW was funded by the Wellcome Trust [Grant No. 098051]. JVL is funded by MRC New Investigator Grant (MR/P002536/1) and ERC Starting Grant (715662). JK is funded by NIHR: II-OL-1116-10027, NIH: R01-CA204403-01A1, Horizon H2020: ITN GROWTH. Imperial Biomedical Research Centre, SAGES research grant. Infrastructure support for this research was provided by the NIHR Imperial biomedical Research Centre (BRC). Microbiota analyses were carried out using the Maxwell computer cluster at the University of Aberdeen. We thank the Illumina MiSeq team at the Wellcome Sanger Institute for their assistance. This work was partially described in the Ph.D. thesis of KD (Retrieved 2020, Pediatric inflammatory bowel disease Monitoring, nutrition and surgery, https://pure.uva.nl/ws/files/23176012/Thesis_complete_.pdf). ",

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AU - Diederen, Kay

AU - Li, Jia V.

AU - Donachie, Gillian E.

AU - de Meij, Tim G.

AU - de Waart, Dirk R.

AU - Hakvoort, Theodorus B. M.

AU - Kindermann, Angelika

AU - Wagner, Josef

AU - Auyeung, Victoria

AU - te Velde, Anje A.

AU - Heinsbroek, Sigrid E. M.

AU - Benninga, Marc A.

AU - Kinross, James

AU - Walker, Alan W.

AU - de Jonge, Wouter J.

AU - Seppen, Jurgen

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N2 - 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.

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KW - INTESTINAL MICROBIOTA

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KW - RECEPTOR

KW - TGR5

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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

Bibliographical note

Keywords

UN SDGs

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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

Bibliographical note

Keywords

UN SDGs

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