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Genome-scale metabolic modelling of the human gut microbiome reveals changes in the glyoxylate and dicarboxylate metabolism in metabolic disorders

Proffitt, Ceri (author)
Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
Bidkhori, Gholamreza (author)
Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
Lee, Sunjae (author)
Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
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Abdellah, Tebani (author)
KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
Mardinoglu, Adil (author)
KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kings Coll London, Fac Dent Oral & Craniofacial Sci
Uhlén, Mathias (author)
KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
Moyes, David L. (author)
Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
Shoaie, Saeed (author)
KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap,Kings Coll London, Fac Dent Oral & Craniofacial Sci
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Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England Science for Life Laboratory, SciLifeLab (creator_code:org_t)
CELL PRESS, 2022
2022
English.
In: ISCIENCE. - : CELL PRESS. - 2589-0042. ; 25:7, s. 104513-
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The human gut microbiome has been associated with metabolic disorders including obesity, type 2 diabetes, and atherosclerosis. Understanding the contri-bution of microbiome metabolic changes is important for elucidating the role of gut bacteria in regulating metabolism. We used available metagenomics data from these metabolic disorders, together with genome-scale metabolic modeling of key bacteria in the individual and community-level to investigate the mecha-nistic role of the gut microbiome in metabolic diseases. Modeling predicted increased levels of glutamate consumption along with the production of ammonia, arginine, and proline in gut bacteria common across the disorders. Abundance profiles and network-dependent analysis identified the enrichment of tartrate dehydrogenase in the disorders. Moreover, independent plasma metabolite levels showed associations between metabolites including proline and tyrosine and an increased tartrate metabolism in healthy obese individuals. We, therefore, propose that an increased tartrate metabolism could be a signifi-cant mediator of the microbiome metabolic changes in metabolic disorders.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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