The gut microbiota modulates host amino acid and glutathione metabolism in mice
Abstract The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtaine...
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Format: | Article |
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Springer Nature
2015-10-01
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Series: | Molecular Systems Biology |
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Online Access: | https://doi.org/10.15252/msb.20156487 |
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author | Adil Mardinoglu Saeed Shoaie Mattias Bergentall Pouyan Ghaffari Cheng Zhang Erik Larsson Fredrik Bäckhed Jens Nielsen |
author_facet | Adil Mardinoglu Saeed Shoaie Mattias Bergentall Pouyan Ghaffari Cheng Zhang Erik Larsson Fredrik Bäckhed Jens Nielsen |
author_sort | Adil Mardinoglu |
collection | DOAJ |
description | Abstract The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from conventionally raised (CONV‐R) and germ‐free (GF) mice using gene expression data and tissue‐specific genome‐scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue‐specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV‐R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism. To validate our predictions, we measured the level of AAs and N‐acetylated AAs in the hepatic portal vein of CONV‐R and GF mice. Finally, we simulated the metabolic differences between the small intestine of the CONV‐R and GF mice accounting for the content of the diet and relative gene expression differences. Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice. |
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issn | 1744-4292 |
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spelling | doaj.art-de5ec72de5a34742b557061fc3c8dbf62024-10-28T09:21:26ZengSpringer NatureMolecular Systems Biology1744-42922015-10-01111011510.15252/msb.20156487The gut microbiota modulates host amino acid and glutathione metabolism in miceAdil Mardinoglu0Saeed Shoaie1Mattias Bergentall2Pouyan Ghaffari3Cheng Zhang4Erik Larsson5Fredrik Bäckhed6Jens Nielsen7Department of Biology and Biological Engineering, Chalmers University of TechnologyDepartment of Biology and Biological Engineering, Chalmers University of TechnologyDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, University of GothenburgDepartment of Biology and Biological Engineering, Chalmers University of TechnologyScience for Life Laboratory, KTH ‐ Royal Institute of TechnologyDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, University of GothenburgDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, University of GothenburgDepartment of Biology and Biological Engineering, Chalmers University of TechnologyAbstract The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from conventionally raised (CONV‐R) and germ‐free (GF) mice using gene expression data and tissue‐specific genome‐scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue‐specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV‐R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism. To validate our predictions, we measured the level of AAs and N‐acetylated AAs in the hepatic portal vein of CONV‐R and GF mice. Finally, we simulated the metabolic differences between the small intestine of the CONV‐R and GF mice accounting for the content of the diet and relative gene expression differences. Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice.https://doi.org/10.15252/msb.20156487genome‐scale metabolic modelsgerm‐free miceglutathione metabolismmetabolomicstranscriptomics |
spellingShingle | Adil Mardinoglu Saeed Shoaie Mattias Bergentall Pouyan Ghaffari Cheng Zhang Erik Larsson Fredrik Bäckhed Jens Nielsen The gut microbiota modulates host amino acid and glutathione metabolism in mice Molecular Systems Biology genome‐scale metabolic models germ‐free mice glutathione metabolism metabolomics transcriptomics |
title | The gut microbiota modulates host amino acid and glutathione metabolism in mice |
title_full | The gut microbiota modulates host amino acid and glutathione metabolism in mice |
title_fullStr | The gut microbiota modulates host amino acid and glutathione metabolism in mice |
title_full_unstemmed | The gut microbiota modulates host amino acid and glutathione metabolism in mice |
title_short | The gut microbiota modulates host amino acid and glutathione metabolism in mice |
title_sort | gut microbiota modulates host amino acid and glutathione metabolism in mice |
topic | genome‐scale metabolic models germ‐free mice glutathione metabolism metabolomics transcriptomics |
url | https://doi.org/10.15252/msb.20156487 |
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