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...

Full description

Bibliographic Details
Main Authors: Adil Mardinoglu, Saeed Shoaie, Mattias Bergentall, Pouyan Ghaffari, Cheng Zhang, Erik Larsson, Fredrik Bäckhed, Jens Nielsen
Format: Article
Language:English
Published: Springer Nature 2015-10-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20156487
_version_ 1827014802655936512
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.
first_indexed 2024-03-07T16:32:01Z
format Article
id doaj.art-de5ec72de5a34742b557061fc3c8dbf6
institution Directory Open Access Journal
issn 1744-4292
language English
last_indexed 2025-02-18T14:14:42Z
publishDate 2015-10-01
publisher Springer Nature
record_format Article
series Molecular Systems Biology
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
work_keys_str_mv AT adilmardinoglu thegutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT saeedshoaie thegutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT mattiasbergentall thegutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT pouyanghaffari thegutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT chengzhang thegutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT eriklarsson thegutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT fredrikbackhed thegutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT jensnielsen thegutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT adilmardinoglu gutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT saeedshoaie gutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT mattiasbergentall gutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT pouyanghaffari gutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT chengzhang gutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT eriklarsson gutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT fredrikbackhed gutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice
AT jensnielsen gutmicrobiotamodulateshostaminoacidandglutathionemetabolisminmice