Integrative analysis of the human genome, metagenome and exposome

Abstract

Human health is not only affected by the intrinsic genome, but also by the microbiome present throughout the body and the extrinsic “exposome” encompassing the totality of human environmental exposures, such as diet, drugs and lifestyles. Here, we presented an integrative analysis of the human genome, metagenome and exposome by analysing comprehensively various genomics, metagenomics and chemoinformatics data. Using systems chemical biology approach, we investigated the interactions between dietary compounds present in plant-based foods with pharmacodynamics (drug targets) and pharmacokinetics (drug-metabolising enzymes, transporters and carriers) processes of FDA-approved drugs. Then the associations between diet and human disease phenotypes were explored using large-scale gene expression dataset, providing new insights on the role of diet in disease development. Moving on to the “hidden organ” gut microbiota, we developed the computational framework for studying, at the molecular-level, diet-gut microbiome interactions, showcasing that individual dietary components may contribute to the observed gene expression activities. And the bacterial genes involved in metabolic pathways and having high centrality in protein-protein interaction network are more “vulnerable” to dietary perturbations. In additional in vivo studies, probiotics treatment in mice was revealed to modulate the gut microbiota, which could in turn not only decrease intra-intestinal polyp formation, but also suppress extra-intestinal hepatocellular carcinoma growth through altered inflammatory responses. To increase the accessibility and awareness of relevant data, as well as to facilitate future investigations, we have developed the NutriChem-2.0 database integrating all together diet–drug–disease interactions aimed at a more comprehensive assessment of dietary effects on human health and drug treatment, and the COMAN web server tool for comprehensive metatranscriptomics data analysis. As an on-going study into physical exercise, another exposome factor, we aim to investigate whether a specific type of exercise intervention could improve glucose tolerance in pre-diabetic people and the role of human gut microbiota in such process. Our aforementioned research is expected to contribute to the personalized therapeutics and intervention strategies that combine human genomic with host-specific microbiome signatures.