摘要：SummaryThe 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.Graphical abstractDisplay OmittedHighlights•Metagenomic analysis highlights key common bacterial species across metabolic diseases•Metabolic models showed higher levels of acetate produced by disease enriched bacteria•Reaction analysis revealed increases in the glyoxylate and dicarboxylate pathway•Metabolomics and modeling analysis showed the potential role of tartrate metabolismMicrobiome; Systems biology; Metabolomics; Omics; Metabolomics
