Project description:Mardinoglu2015 - Generic mouse genome-scale
metabolic network (MMR)
This model is described in the article:
The gut microbiota modulates
host amino acid and glutathione metabolism in mice.
Mardinoglu A, Shoaie S, Bergentall
M, Ghaffari P, Zhang C, Larsson E, Bäckhed F, Nielsen
Mol. Syst. Biol. 2015; 11(10):
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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Project description:Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This study found that age-associated changes of the gut microbiome of BALB/c and C57BL/6 mice could be reverted by co-housing of aged (22 months old) and adult (3 months old) mice for 30-40 days or faecal microbiota transplantation (FMT) from adult into aged mice. This was demonstrated using high-throughput sequencing of the V3-V4 hypervariable region of bacterial 16S rRNA gene isolated from faecal pellets collected from 3-4 months old adult and 22-23 months old aged mice before and after co-housing or FMT.