Virtual Metabolic Human: a comprehensive metabolic resource of human, human associated microbes and disease

The number of Genome Scale Metabolic Models (GEMs) has been increasing with the availability of genomic data, and they range from bacteria to human(1, 2), and specific cell types(3). This has brought to light the potential of these models for predictive biology and particularly for biomedical purposes(4). Another application of this modeling technique, also currently on the spotlight, is tackling the complexity of the gut microbiome. In fact, the microbiome community in our intestine alone consists of thousands of species with a collective genome 150 times greater than our own (5), and the COBRA approach can be used to systematically study the interactions between microbes and host. This can enable a better understanding of the metabolism of humans and microbes, but more importantly, it has the potential to provide insights to the community behavior, such as how do the microbes cooperate/compete between themselves(6), and their influence in health and disease.

The Virtual Metabolic Human (VMH) is a freely available database that combines human metabolism, human associated microbes and disease. It includes the most recent version of the human metabolic reconstruction that comprehensibly describes all known metabolic processes and accounts for more than 7000 metabolic and transport reactions, almost 1700 genes encoding for those reactions, and over 2600 unique metabolites. A collection of semi-curated metabolic reconstructions of human gut microbes is also available. Having the metabolism of microbes and the human host combined in one database will allow more comprehensive scientific questions, such as metabolites unique to the microbiota, reactions/enzymes unique to the human providing potential microbial specific drug targets. Finally, a manually assembled compendium of 250 inherited metabolic disease, which are individually rare but collectively frequent (1:800 life birth). The database permits to connect the knowledge about biomarkers and disease responsible genes with the broader context of human metabolism.

The VMH database has been online since 2013 but contained up to now it only contained the human metabolic resource. We expect that by capturing gut microbial metabolic information as well as information on biofluids, biomarkers, and inherited metabolic diseases, the VMH will attract an even larger scientific community.

1.            Duarte NC, Becker SA, Jamshidi N, Thiele I, Mo ML, Vo TD, et al. Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proceedings of the National Academy of Sciences. 2007;104(6):1777-82.

2.            Thiele I, Swainston N, Fleming RM, Hoppe A, Sahoo S, Aurich MK, et al. A community-driven global reconstruction of human metabolism. Nature biotechnology. 2013;31(5):419-25.

3.            Sahoo S, Thiele I. Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells. Human molecular genetics. 2013;22(13):2705-22.

4.            Sahoo S, Franzson L, Jonsson JJ, Thiele I. A compendium of inborn errors of metabolism mapped onto the human metabolic network. Molecular bioSystems. 2012;8(10):2545-58.

5.            Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65.

6.            Heinken A, Thiele I. Anoxic Conditions Promote Species-Specific Mutualism between Gut Microbes In Silico. Applied and environmental microbiology. 2015;81(12):4049-61.