The gut microbiota modulates host amino acid and glutathione metabolism in mice
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The gut microbiota modulates host amino acid and glutathione metabolism in mice. / Mardinoglu, Adil; Shoaie, Saeed; Bergentall, Mattias; Ghaffari, Pouyan; Zhang, Cheng; Larsson, Erik; Bäckhed, Gert Fredrik; Nielsen, Jens.
In: Molecular Systems Biology, Vol. 11, No. 10, 834, 2015, p. 1-15.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The gut microbiota modulates host amino acid and glutathione metabolism in mice
AU - Mardinoglu, Adil
AU - Shoaie, Saeed
AU - Bergentall, Mattias
AU - Ghaffari, Pouyan
AU - Zhang, Cheng
AU - Larsson, Erik
AU - Bäckhed, Gert Fredrik
AU - Nielsen, Jens
N1 - © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.15252/msb.20156487
DO - 10.15252/msb.20156487
M3 - Journal article
C2 - 26475342
VL - 11
SP - 1
EP - 15
JO - Molecular Systems Biology
JF - Molecular Systems Biology
SN - 1744-4292
IS - 10
M1 - 834
ER -
ID: 150712599