The gut microbiota modulates host amino acid and glutathione metabolism in mice
Journal article, 2015

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.

metabolomics

transcriptomics

genome-scale metabolic models

germ-free mice

glutathione metabolism

Author

Adil Mardinoglu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Saeed Shoaie

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Mattias Bergentall

University of Gothenburg

Pouyan Ghaffari Nouran

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

C. Zhang

Royal Institute of Technology (KTH)

E. G. Larsson

University of Gothenburg

Fredrik Bäckhed

University of Gothenburg

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Molecular Systems Biology

1744-4292 (ISSN)

Vol. 11 10 Article Number: 834- 834

Metagenomics in Cardiometabolic Diseases (METACARDIS)

European Commission (FP7), 2012-11-01 -- 2017-10-31.

Subject Categories

Biochemistry and Molecular Biology

Cell and Molecular Biology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.15252/msb.20156487

PubMed

26475342

More information

Latest update

2/26/2018