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

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.

Automated summary

The human gut microbiome is associated with metabolic disorders such as obesity, type 2 diabetes, and atherosclerosis. The study investigated the role of gut bacteria in metabolic diseases using metagenomics data and metabolic modeling. The modeling predicted changes in glutamate consumption and the production of ammonia, arginine, and proline in gut bacteria common across the disorders. The study also found that tartrate dehydrogenase is enriched in the disorders and an increased tartrate metabolism is associated with certain metabolites in healthy obese individuals.