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Host-Microbe Co-Metabolism

What are the functional consequences of changes in the human gut microbiota in health and disease?

Using the COBRA approach, we have generated the first physiologically resolved whole-body, gender-specific metabolic models (WBMs) based on extensive organ-specific proteomic and metabolomic data, as well as through literature curation. The WBMs capture the metabolism of 26 anatomically interconnected


organs, the gastrointestinal lumen, the systemic blood circulation, and the blood-brain barrier, represented by >80,000 reactions, >50,000 metabolites, and >1,700 gene products. We have demonstrated that the WBMs could accurately predict known blood biomarker metabolites for 57 inherited metabolic diseases. We have also generated >800 genome-scale gut microbial metabolic models containing 205 genera and 605 species based on literature-derived experimental data. The microbial models have been combined into a generic microbial community model and integrated with the WBMs. These generic microWBMs can be personalised based on, e.g., metagenomic, genetic, physiological, and dietary data. In average, 90% of the reads can be mapped onto the captured microbial genomes.

We use personalised microWBMs to systematically investigate host-microbiome co-metabolism, with particular emphasis along the diet-gut-brain axis.

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