The gut microbiota modulates host amino acid and glutathione metabolism in mice
Open accessAbstract
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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Germ-free mice retain significantly higher amounts of arginine in their intestines than mice colonized by gut microbes.
“Germ-free mice retain significantly higher amounts of arginine in their intestines than mice colonized by gut microbes.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Mardinoglu et al., 2015
The microbiome metabolizes substantial quantities of dietary arginine and may regulate arginine availability to the immune system to some extent.
“This indicates that the microbiome metabolizes substantial quantities of dietary arginine and may thus regulate the availability of arginine to the immune system to a certain extent (Mardinoglu et al., 2015; Matsumoto et al., 2012).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Mardinoglu et al., 2015
The composition and concentration of amino acids may play a pivotal role in proteolytic fermentation by the gut microbiota in the small intestine, which influences amino-acid homeostasis.
“This evidence indicates that the composition and concentration of amino acids may play a pivotal role in the proteolytic fermentation by the gut microbiota in the small intestine, which influences amino-acid homeostasis [159,160].”
From Impact of Protein Intake in Older Adults with Sarcopenia and Obesity: A Gut Microbiota Perspective (2020) · cites this paper as [159]
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- Authors
- Mardinoglu, A., Shoaie, S., Bergentall, M., Ghaffari, P., Zhang, C., Larsson, E., Bäckhed, F., & Nielsen, J.
- Affiliations
- Chalmers University of Technology (SE)
- University of Copenhagen (DK)
- Science for Life Laboratory (SE)
- Venue
- Molecular Systems Biology
- Published
- 2015-10-01
- Volume
- 11
- Issue
- 10
- Pages
- 834-834
- ISSN
- 1744-4292 (ISSN-L)
- PMC
- PMC4631205
- OpenAlex
- W2142500268
- Cited by
- 383
- References
- 70
- Citations by year
- 2026: 20 · 2025: 33 · 2024: 37 · 2023: 32 · 2022: 38 · 2021: 49 · 2020: 51 · 2019: 44 · 2018: 28 · 2017: 26 · 2016: 24 · 2015: 1
- FWCI
- 11.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Systems Biology (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Chalmers Publication Library (Chalmers University of Technology) (submittedVersion)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Bill & Melinda Gates Foundation
- Knut and Alice Wallenberg Foundation
- Torsten Söderbergs Stiftelse
- European Commission FP7 project METACARDIS (HEALTH‐F4‐2012‐305312)
- Novo Nordisk A/S
- Novo Nordisk Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- gut microbiota, germ-free mice, amino acid metabolism, glutathione metabolism, portal vein, N-acetylated amino acids, host-microbe interactions, metabolic disorders
- MeSH terms
- Amino Acids, Animals, Glutathione, Intestine, Small, Male, Mice, Inbred C57BL, Mice, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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