BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509220018?filename=MODEL1509220018.pdfhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509220018?filename=MODEL1509220018-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509220018?filename=MODEL1509220018-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509220018?filename=MODEL1509220018_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509220018?filename=MODEL1509220018_urn.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509220018?filename=MODEL1509220018.scihttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509220018?filename=MODEL1509220018.pngprimaryOK200Nicolas RodriguezNon-curatedL2V3https://www.ebi.ac.uk/biomodels/MODEL150922001826475342falseBioModelsSBMLModelsMardinoglu2015 Tissue specific genome scale metabolic network Midbrain2015MODEL1509220018Non KineticAdil Mardinoglu, Saeed Shoaie, Mattias Bergentall, Pouyan Ghaffari, Cheng Zhang, Erik Larsson, Fredrik Bäckhed, Jens NielsenAdil Mardinoglu26475342,
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.. 10, 11.
Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden adilm@scilifelab.se.rodrigue@ebi.ac.ukEMBL-EBIThe 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.The gut microbiota modulates host amino acid and glutathione metabolism in mice.Mardinoglu Adil A, Shoaie Saeed S, Bergentall Mattias M, Ghaffari Pouyan P, Zhang Cheng C, Larsson Erik E, Bäckhed Fredrik F, Nielsen Jens Jscale tissue, mesencephalon, scale, Midbrain, Genomes, Midbrains, plant peltate hair, peltate hair, Tissue, simple tissue, MB, whole genome, scales, Mesencephalons.biochemical pathways, extent, host organism, scale tissue, mesencephalon, Metabolic Process, Food Patterns, BODYFAT, Bowel, Materials, Public Sectors, Laboratory, Aminosaeure, Mus domesticus, Metabolic Concepts, mental retardation, nip, l(2)k14019, CASP-14, cd206, composed of, House Mouse, lower intestine, Small, Taenia Coli, Appendix, B1, gamma-L-Glutamyl-L-cysteinyl-glycine, l(2)SH1330, middle intestine, Concepts, AAS, Metabolism Concept, Public Enterprise, fatty tissue, Phenomenon, small intestine, fat tissue, vena portae hepatis, Omental Appendix, CT15952, Thesaurismosis, amino acids, Gene Expressions, Genomes, adipose system, catabolism, Glycine, plant peltate hair, Reduced, HPV, Microbial Community Structure, Metabolic disease, 5-L-Glutamyl-L-cysteinylglycine, Public Domains, Tissue, alimentary tract, iecur, Swiss Mice, 35Bb, composition, metabolic process resulting in cell growth, free, Glutathione, Food, Reduced glutathione, Intestines, reaction, anterior intestine, DmelCG4974, g, CG3183, Microbial Community Structures, anon-WO0257455.1, digestive tube, GL2-EXPRESSION MODULATOR, biotransformation, asd, METABOLISM DISORDER NOS, house mouse, adult alimentary canal, alimentary system, MD - Metabolic disorders, CD206, l(3)06464, Catabolism, Small Intestine, upper intestine, syndromic 16, Process, completeness, Aminokarbonsaeure, metabolism resulting in cell growth, mouse, gamma-L-Glu-L-Cys-Gly, Microbial, Appendix Epiploica, faciogenital dysplasia with attention 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Community, 3.4.22.-, White Adipose, digestive canal, Microbial Community Composition, AW546347, Gems, Sectors, intestinum ileum, Metabolic Disease, X-linked, primary hepatic portal vein, mol, anon-EST:Liang-1.63, Peptidomics, Processes, peltate hair, Aminocarbonsaeure, number, enteric tract, Gene, mini-ICE, Gm695, gamma-L-Glutamyl-L-Cysteinylglycine, Copyrights, fat, Metabolic Processes, C-type lectin domain family 13 member D-like, DmelCG4482, presence, Patterns, Human, jecur, N-(N-L-gamma-glutamyl-L-cysteinyl)-, Gus, Gur, intestinum jejunum, Gut, Generalized metabolic disorder, House, Metabolism, Gem, Diets, Mus musculus domesticus, metabolism disorder, Mice, Metabolism Phenomena, Enterprises, l(2)br23, Generalized metabolic disorder (disorder), mid intestine, disease of metabolism, gut, intestinum duodenum, MutS/MutL/MutH pathway, Aarskog Scott syndrome, Genetic, Food Pattern, clec13d, Swiss, Accountings, gem, posterior intestine, Metabolic Concept, N-(N-gamma-L-Glutamyl-L-cysteinyl)glycine, Public Enterprises, Expressions, Duodenums, MRC1L1, gamma L Glutamyl L Cysteinylglycine, Pattern, Abstract, l(3)SG18, gamma L Glu L Cys Gly, bodyfat, Metabolic disorder, Dm Geminin, primary hepatic portal veins, Expression, clone 1.63, Dietary Pattern, Enterprise, intestines, CG3459, textus adiposus albus, Human Microbiome, Disease, Community Composition, degradation, CG4482, DmelCG30011, l(2)35Bb, MRXS16, MB, Dm geminin, v(2)k09107, compositionality, disorder of metabolism NOS (disorder), Cistrons, hindgut, Concept, Metabolic Phenomena, gut tube, Metabolism Concepts, count in organism, Mus, Public, disorder of metabolism NOS, Mesencephalons, Generalised metabolic disorder, Phenomena, scales, metabolism, Reduced Glutathione, alimentary canal, Data Base, Metabolic disorders, Metabolic Phenomenon, Microbiome, Metabolic disease (disorder), multicellular organism metabolic process, distal intestine, Microbiomes, scale, biodegradation, Thesaurismoses, Metabolic, Microbial Community, metabolic disease, Dietary, coiled body, Gus-u, Community Structure, Gus-t, Gus-s, Small Intestines, Gus-r, House Mice, MutL-like pathway, Omental, CG15268, Amino, small bowel, AV020497, included, Laboratory Mice, Jejunums, br3, Livers, CLEC13D, Metabolic Diseases, fatty depot, Midbrains, adipose, mid-intestine, structure, Microbiotas, NIP, Glutathione-SH, Public., geminin, Laboratory Mouse, Gemini of coiled bodies, anon-AE003830.1, AnabolismEnteric Microflora, 3.4.22.-, host organism, Gastric Microbiomes, Intestinal Microbiomes, Gut Microbiomes, Enteric, Microflora Floras, Gastrointestinal Microbiota, Gut Microbiome, Laboratory, Gastrointestinal, Aminokarbonsaeure, Aminosaeure, Mus domesticus, Microfloras, Aminocarbonsaeure, mouse, Microbiota, mini-ICE, CASP-14, Gastrointestinal Microbiotas, Gut Microflora, Gastrointestinal Flora, House Mouse, Intestinal Flora, Gastrointestinal Microbial Communities, GI Microflora, Floras, GI Microbiome, 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Aminosaeure, Metabolic Concepts, mental retardation, l(2)k14019, CASP-14, cd206, sci, Gut Microflora, House Mouse, Gastrointestinal Microbial Communities, GI Microbiome, lower intestine, Small, Taenia Coli, Appendix, HOW, How, middle intestine, Concepts, AAS, Flora, Metabolism Concept, fatty tissue, Phenomenon, small intestine, l(3)j5D5, fat tissue, vena portae hepatis, 24B, Omental Appendix, CT15952, Thesaurismosis, amino acids, Gene Expressions, Genomes, adipose system, catabolism, Moods, plant peltate hair, HPV, Metabolic disease, Tissue, stru, iecur, Swiss Mice, metabolic process resulting in cell growth, l(3)S053606, CG10293, Food, l(3)j5B5, Intestines, reaction, anterior intestine, DmelCG4974, CG3183, anon-WO0257455.1, GL2-EXPRESSION MODULATOR, biotransformation, METABOLISM DISORDER NOS, house mouse, MD - Metabolic disorders, CD206, l(3)06464, Catabolism, Small Intestine, upper intestine, 0904/17, Intestinal Microbiomes, syndromic 16, Process, Gut Microbiome, Aminokarbonsaeure, metabolism resulting in cell growth, mouse, Microbiota, Appendix Epiploica, faciogenital dysplasia with attention Deficit-hyperactivity disorder, GI Microflora, CG30011, portal vein, Floras, Intestinal Microbiota, Body Fat, dodecadactylon, SZ1, adp, Mini-ICE, Diseases, dCP2, Intestinal Microbiotas, NOS, MMR, secretion, simple tissue, KIR, proximal intestine, macrophage mannose receptor 1-like protein 1, oxidized glutathione reduction, Omental Appendices, CLEC13DL, DmelCG3183, Mus musculus, long patch mismatch repair system, Amino Acid, Acid, METAB DIS, CG11867, Caspase-14 subunit p10, mismatch repair, mice, Swiss Mouse, mmr, CG4974, Appendices, Caspase-14 subunit p19, White Adipose Tissue, whole genome, Dally, Enteric Microbiota, White Fat, MICE, Geminin, domesticus, Gastrointestinal Microflora, intestinum tenue, GI, BcDNA:HL07889, Dietary Patterns, COLON, Enteric Microflora Floras, anon-EST:Liang-2.39, White, Mouse, Acids, Unspecified disorder of metabolism, Fat, Gastric Microbiome, White Adipose, 3.4.22.-, Gastric Microbiomes, AW546347, Gems, Gut Microbiomes, intestinum ileum, Microflora Floras, Metabolic Disease, X-linked, primary hepatic portal vein, anon-EST:Liang-1.63, Peptidomics, Gastrointestinal, Processes, P62, peltate hair, Microfloras, Aminocarbonsaeure, Gene, mini-ICE, Gm695, fat, Gastrointestinal Flora, Metabolic Processes, C-type lectin domain family 13 member D-like, Patterns, jecur, intestinum jejunum, Gut, environment factor, Generalized metabolic disorder, House, Metabolism, Gem, Diets, metabolism disorder, Mus musculus domesticus, Gut Microbiotas, Mood, Mice, Metabolism Phenomena, Generalized metabolic disorder (disorder), GI Microfloras, mid intestine, disease of metabolism, l(3)s2612, intestinum duodenum, MutS/MutL/MutH pathway, Aarskog Scott syndrome, Food Pattern, clec13d, Swiss, Accountings, gem, Enteric Bacteria, posterior intestine, Metabolic Concept, Bacteria, Expressions, Duodenums, MRC1L1, Gut Flora, Pattern, l(3)SG18, DmelCG10293, bodyfat, Gastrointestinal Microbial Community, Metabolic disorder, Dm Geminin, primary hepatic portal veins, Expression, clone 1.63, Dietary Pattern, CG3459, textus adiposus albus, Enteric Microflora, Disease, Enteric, degradation, clone 2.39, DmelCG30011, Affects, MRXS16, Dm geminin, v(2)k09107, Gastrointestinal Microbiotas, qkr, disorder of metabolism NOS (disorder), l(3)S090417, hindgut, Intestinal Flora, Concept, Metabolic Phenomena, Metabolism Concepts, Enteric Microbiotas, Mus, disorder of metabolism NOS, KH93F, Gastrointestinal Microbiomes, Generalised metabolic disorder, Phenomena, Gut Microbiota, scales, Microflora Flora, Gastric, metabolism, Mus musculus., Metabolic disorders, Metabolic Phenomenon, Microbiome, who, Metabolic disease (disorder), multicellular organism metabolic process, Intestinal Microflora, distal intestine, Microbiomes, Microflora, scale, biodegradation, Thesaurismoses, Metabolic, Microbial Community, metabolic disease, Dietary, coiled body, Small Intestines, House Mice, MutL-like pathway, Who/How, Omental, Amino, Intestinal Microbiome, small bowel, AV020497, included, Laboratory Mice, Enteric Microflora Flora, Jejunums, Livers, CLEC13D, Metabolic Diseases, fatty depot, adipose, mid-intestine, Intestinal, qkr[93F], Microbiotas, geminin, Laboratory Mouse, Gemini of coiled bodies, GI Microbiomes, anon-AE003830.1, AnabolismfalseMardinoglu2015 - Tissue-specific genome-scale metabolic network - Midbrain
Mardinoglu2015 - Tissue-specific genome-scale
metabolic network - Midbrain
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
J.
Mol. Syst. Biol. 2015; 11(10):
834
Abstract:
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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2015-10-302015-11-042015-09-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.2.4.12.3.1.121.8.1.41.2.1.511.1.1.11.1.1.26.2.1.11.2.1.51.2.1.31.2.1.495.4.2.65.4.2.25.2.2.25.4.2.51.1.1.215.1.3.32.7.1.12.7.1.21.1.2.41.11.1.63.1.2.26.2.1.171.3.99.33.2.1.201.1.1.221.17.1.44.1.1.91.17.3.22.4.1.1862.4.2.152.4.2.12.4.1.111.2.1.181.2.1.272.4.2.222.4.2.82.4.1.182.4.1.13.5.4.42.4.2.42.4.1.253.2.1.333.1.3.51.1.1.-3.1.2.43.2.1.16.3.4.132.3.1.96.2.1.166.3.3.14.1.1.211.1.1.306.3.5.36.3.2.62.3.3.101.1.1.274.3.2.22.1.2.32.7.6.11.1.1.492.7.1.482.7.4.83.1.1.313.6.1.533.6.1.131.1.1.442.7.4.62.7.1.155.3.1.65.4.2.74.1.2.42.2.1.15.1.3.13.2.1.33.2.1.102.7.4.102.2.1.22.7.1.1062.7.7.92.7.1.62.7.4.143.6.1.53.6.1.63.2.1.484.6.1.14.6.1.22.7.4.33.2.1.1083.2.1.233.2.1.222.6.1.401.8.1.92.7.1.34.1.2.132.7.1.742.7.1.202.7.4.41.1.1.146.3.4.23.1.4.176.3.5.54.1.1.233.5.4.102.1.3.25.3.1.85.4.2.83.1.3.351.1.1.2056.3.4.42.7.7.222.7.7.136.3.5.23.1.4.353.6.1.83.6.1.93.6.1.454.2.1.471.1.1.2713.5.4.63.5.4.172.7.1.-3.6.1.423.6.1.192.4.2.92.4.2.141.3.1.21.1.1.103.5.2.21.1.1.151.7.1.71.1.1.92.7.1.1471.1.1.452.7.1.112.4.2.106.3.4.12.7.4.113.5.2.31.2.1.43.1.3.111.3.1.141.3.5.23.1.3.-2.7.4.92.7.4.124.4.1.55.3.1.13.6.1.231.2.1.123.1.2.62.7.2.32.1.1.453.6.1.75.4.2.15.4.2.43.1.3.131.17.4.11.1.1.391.1.1.381.1.1.404.2.1.112.7.1.403.5.4.34.1.1.326.4.1.12.7.1.1132.7.4.251.1.1.811.1.1.793.4.11.23.4.11.12.5.1.183.6.5.53.6.5.13.6.5.33.6.5.23.6.5.63.6.5.41.2.1.881.1.1.2112.3.1.161.13.11.342.3.1.1991.3.1.392.1.3.856.2.1.32.3.2.42.3.2.22.3.1.412.3.1.1792.3.1.851.1.1.3302.1.1.62.3.1.72.7.7.43.3.2.93.3.2.101.5.1.24.1.1.224.1.1.281.3.3.62.7.1.25TCDB:2.A.29.8.31.1.1.1002.3.1.863.5.1.264.1.1.154.1.1.114.2.1.594.2.1.172.1.1.81.3.1.-1.1.1.352.6.1.192.6.1.553.2.1.966.3.2.112.7.1.761.4.3.42.1.1.283.4.13.33.4.13.203.2.1.522.1.2.21.1.1.1841.5.99.82.3.1.1371.4.3.211.4.3.221.4.3.61.13.11.314.2.1.14.3.1.31.14.13.302.7.10.22.7.12.12.7.10.12.7.12.22.7.7.522.7.7.62.7.7.192.7.7.83.1.3.481.1.1.2324.1.1.501.11.1.94.4.1.163.5.3.154.4.1.13.5.1.-2.5.1.164.2.1.223.2.2.193.3.1.12.5.1.-1.3.8.91.3.8.71.3.8.81.14.13.81.3.1.345.3.3.81.14.19.12.5.1.62.1.1.93.1.2.224.1.1.172.3.1.1545.1.99.42.6.1.12.3.1.393.1.2.143.1.2.216.4.1.21.4.3.101.2.1.253.1.3.71.3.8.11.3.99.122.6.1.572.6.1.52.1.1.21.13.11.271.13.11.51.2.4.23.3.2.63.4.11.65.2.1.21.13.11.121.13.11.331.5.8.43.1.2.173.7.1.21.5.1.83.4.13.182.3.1.212.3.1.-1.1.1.2221.1.1.2371.14.14.16.2.1.51.3.8.46.2.1.121.14.11.22.6.1.393.1.2.236.4.1.44.2.1.181.1.1.1412.1.1.491.5.1.92.4.1.172.6.1.221.2.1.312.8.3.51.1.1.1781.11.1.71.2.4.41.1.1.421.11.1.81.11.2.22.3.1.612.7.7.233.5.99.62.1.1.432.6.1.161.1.1.412.8.2.-2.6.1.233.1.6.21.14.19.-2.7.1.595.1.3.141.14.13.344.1.3.164.2.1.1343.4.21.892.4.2.281.3.1.932.7.1.602.5.1.562.5.1.572.3.1.571.14.11.83.1.3.291.1.1.371.14.18.2spontaneous2.1.2.12.7.7.431.2.1.471.6.5.52.3.1.42.3.3.12.3.3.33.5.1.251.14.16.15.4.2.36.2.1.42.3.1.131.5.3.71.5.3.16.1.1.12.3.3.86.1.1.76.1.1.196.1.1.222.6.1.36.1.1.126.1.1.162.1.1.132.8.1.26.1.1.186.1.1.175.3.99.25.3.99.31.8.3.16.1.1.144.2.1.36.1.1.214.4.1.86.1.1.56.1.1.45.3.1.234.2.1.1096.1.1.66.1.1.103.1.3.771.13.11.541.13.11.536.1.1.206.1.1.156.1.1.116.1.1.36.1.1.21.4.1.33.1.1.233.1.1.346.1.1.92.8.1.12.5.1.103.1.1.36.3.4.51.14.99.12.6.1.71.8.1.74.3.2.11.11.1.151.3.5.14.4.1.222.4.1.834.1.-.-3.2.1.241.5.3.131.5.3.166.2.1.241.1.1.2843.2.1.253.1.2.121.14.11.183.4.11.43.4.19.53.4.16.53.2.1.181.2.1.396.3.2.23.1.6.46.3.2.32.6.1.216.3.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