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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

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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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