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Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology
BACKGROUND: Methionine, a central molecule in one-carbon metabolism, is an essential amino acid required for normal growth and development. Despite its importance to biological systems, methionine is toxic when administered at supra-physiological levels. The aim of this study was to investigate the...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588631/ https://www.ncbi.nlm.nih.gov/pubmed/28904640 http://dx.doi.org/10.1186/s12263-017-0576-0 |
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author | Miousse, Isabelle R. Pathak, Rupak Garg, Sarita Skinner, Charles M. Melnyk, Stepan Pavliv, Oleksandra Hendrickson, Howard Landes, Reid D. Lumen, Annie Tackett, Alan J. Deutz, Nicolaas E.P. Hauer-Jensen, Martin Koturbash, Igor |
author_facet | Miousse, Isabelle R. Pathak, Rupak Garg, Sarita Skinner, Charles M. Melnyk, Stepan Pavliv, Oleksandra Hendrickson, Howard Landes, Reid D. Lumen, Annie Tackett, Alan J. Deutz, Nicolaas E.P. Hauer-Jensen, Martin Koturbash, Igor |
author_sort | Miousse, Isabelle R. |
collection | PubMed |
description | BACKGROUND: Methionine, a central molecule in one-carbon metabolism, is an essential amino acid required for normal growth and development. Despite its importance to biological systems, methionine is toxic when administered at supra-physiological levels. The aim of this study was to investigate the effects of short-term methionine dietary modulation on the proximal jejunum, the section of the gut specifically responsible for amino acid absorption, in a mouse model. Eight-week-old CBA/J male mice were fed methionine-adequate (MAD; 6.5 g/kg) or methionine-supplemented (MSD; 19.5 g/kg) diets for 3.5 or 6 days (average food intake 100 g/kg body weight). The study design was developed in order to address the short-term effects of the methionine supplementation that corresponds to methionine dietary intake in Western populations. Biochemical indices in the blood as well as metabolic, epigenetic, transcriptomic, metagenomic, and histomorphological parameters in the gut were evaluated. RESULTS: By day 6, feeding mice with MSD (protein intake <10% different from MAD) resulted in increased plasma (2.3-fold; p < 0.054), but decreased proximal jejunum methionine concentrations (2.2-fold; p < 0.05) independently of the expression of neutral amino acid transporters. MSD has also caused small bowel bacteria colonization, increased the abundance of pathogenic bacterial species Burkholderiales and decreased the gene expression of the intestinal transmembrane proteins—Cldn8 (0.18-fold, p < 0.05), Cldn9 (0.24-fold, p < 0.01) and Cldn10 (0.05-fold, p < 0.05). Feeding MSD led to substantial histomorphological alterations in the proximal jejunum exhibited as a trend towards decreased plasma citrulline concentrations (1.8-fold, p < 0.07), as well as loss of crypt depth (by 28%, p < 0.05) and mucosal surface (by 20%, p < 0.001). CONCLUSIONS: Together, these changes indicate that short-term feeding of MSD substantially alters the normal gut physiology. These effects may contribute to the pathogenesis of intestinal inflammatory diseases and/or sensitize the gut to exposure to other stressors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12263-017-0576-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5588631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55886312017-09-13 Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology Miousse, Isabelle R. Pathak, Rupak Garg, Sarita Skinner, Charles M. Melnyk, Stepan Pavliv, Oleksandra Hendrickson, Howard Landes, Reid D. Lumen, Annie Tackett, Alan J. Deutz, Nicolaas E.P. Hauer-Jensen, Martin Koturbash, Igor Genes Nutr Research BACKGROUND: Methionine, a central molecule in one-carbon metabolism, is an essential amino acid required for normal growth and development. Despite its importance to biological systems, methionine is toxic when administered at supra-physiological levels. The aim of this study was to investigate the effects of short-term methionine dietary modulation on the proximal jejunum, the section of the gut specifically responsible for amino acid absorption, in a mouse model. Eight-week-old CBA/J male mice were fed methionine-adequate (MAD; 6.5 g/kg) or methionine-supplemented (MSD; 19.5 g/kg) diets for 3.5 or 6 days (average food intake 100 g/kg body weight). The study design was developed in order to address the short-term effects of the methionine supplementation that corresponds to methionine dietary intake in Western populations. Biochemical indices in the blood as well as metabolic, epigenetic, transcriptomic, metagenomic, and histomorphological parameters in the gut were evaluated. RESULTS: By day 6, feeding mice with MSD (protein intake <10% different from MAD) resulted in increased plasma (2.3-fold; p < 0.054), but decreased proximal jejunum methionine concentrations (2.2-fold; p < 0.05) independently of the expression of neutral amino acid transporters. MSD has also caused small bowel bacteria colonization, increased the abundance of pathogenic bacterial species Burkholderiales and decreased the gene expression of the intestinal transmembrane proteins—Cldn8 (0.18-fold, p < 0.05), Cldn9 (0.24-fold, p < 0.01) and Cldn10 (0.05-fold, p < 0.05). Feeding MSD led to substantial histomorphological alterations in the proximal jejunum exhibited as a trend towards decreased plasma citrulline concentrations (1.8-fold, p < 0.07), as well as loss of crypt depth (by 28%, p < 0.05) and mucosal surface (by 20%, p < 0.001). CONCLUSIONS: Together, these changes indicate that short-term feeding of MSD substantially alters the normal gut physiology. These effects may contribute to the pathogenesis of intestinal inflammatory diseases and/or sensitize the gut to exposure to other stressors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12263-017-0576-0) contains supplementary material, which is available to authorized users. BioMed Central 2017-09-06 /pmc/articles/PMC5588631/ /pubmed/28904640 http://dx.doi.org/10.1186/s12263-017-0576-0 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Miousse, Isabelle R. Pathak, Rupak Garg, Sarita Skinner, Charles M. Melnyk, Stepan Pavliv, Oleksandra Hendrickson, Howard Landes, Reid D. Lumen, Annie Tackett, Alan J. Deutz, Nicolaas E.P. Hauer-Jensen, Martin Koturbash, Igor Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology |
title | Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology |
title_full | Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology |
title_fullStr | Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology |
title_full_unstemmed | Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology |
title_short | Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology |
title_sort | short-term dietary methionine supplementation affects one-carbon metabolism and dna methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588631/ https://www.ncbi.nlm.nih.gov/pubmed/28904640 http://dx.doi.org/10.1186/s12263-017-0576-0 |
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