Personalized whole‐body models integrate metabolism, physiology, and the gut microbiome
Open Access
- 28 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Systems Biology
- Vol. 16 (5), e8982
- https://doi.org/10.15252/msb.20198982
Abstract
Comprehensive molecular‐level models of human metabolism have been generated on a cellular level. However, models of whole‐body metabolism have not been established as they require new methodological approaches to integrate molecular and physiological data. We developed a new metabolic network reconstruction approach that used organ‐specific information from literature and omics data to generate two sex‐specific whole‐body metabolic (WBM ) reconstructions. These reconstructions capture the metabolism of 26 organs and six blood cell types. Each WBM reconstruction represents whole‐body organ‐resolved metabolism with over 80,000 biochemical reactions in an anatomically and physiologically consistent manner. We parameterized the WBM reconstructions with physiological, dietary, and metabolomic data. The resulting WBM models could recapitulate known inter‐organ metabolic cycles and energy use. We also illustrate that the WBM models can predict known biomarkers of inherited metabolic diseases in different biofluids. Predictions of basal metabolic rates, by WBM models personalized with physiological data, outperformed current phenomenological models. Finally, integrating microbiome data allowed the exploration of host–microbiome co‐metabolism. Overall, the WBM reconstructions, and their derived computational models, represent an important step toward virtual physiological humans.Keywords
This publication has 95 references indexed in Scilit:
- A Whole-Cell Computational Model Predicts Phenotype from GenotypeCell, 2012
- Multiscale Modeling and Data Integration in the Virtual Physiological Rat ProjectAnnals of Biomedical Engineering, 2012
- A framework for human microbiome researchNature, 2012
- The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian ColonCell Metabolism, 2011
- Functional Characterization of Alternate Optimal Solutions of Escherichia coli's Transcriptional and Translational MachineryBiophysical Journal, 2010
- What is flux balance analysis?Nature Biotechnology, 2010
- A protocol for generating a high-quality genome-scale metabolic reconstructionNature Protocols, 2010
- HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiologyMolecular Systems Biology, 2010
- Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypesMolecular Systems Biology, 2008
- Factors that influence the cutaneous synthesis and dietary sources of vitamin DArchives of Biochemistry and Biophysics, 2007