Adil Mardinoğlu1,2, Saeed Shoaie1, Mattias Bergentall3,4, Pouyan Ghaffari1, Cheng Zhang2, Erik Larsson3,4, Fredrik Bäckhed3,4, Jens Nielsen1,2
1Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
2Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden
3Department of Molecular and Clinical Medicine Wallenberg Laboratory University of Gothenburg Gothenburg Sweden
4Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Tóm tắt
AbstractThe 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.
