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

Ceri Proffitt, Gholamreza Bidkhori, Sunjae Lee, Abdellah Tebani, Adil Mardinoglu, Mathias Uhlen, David L. Moyes, Saeed Shoaie*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

The human gut microbiome has been associated with metabolic disorders including obesity, type 2 diabetes, and atherosclerosis. Understanding the contribution 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 mechanistic 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 significant mediator of the microbiome metabolic changes in metabolic disorders.

Original languageEnglish
Article number104513
JournaliScience
Volume25
Issue number7
DOIs
Publication statusPublished - 15 Jul 2022

Keywords

  • Metabolomics
  • Microbiome
  • Omics
  • Systems biology

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