Whole-body systems approaches for gut microbiota-targeted, preventive healthcare.

Humans are superorganisms with two genomes that dictate phenotype, the genetically inherited human genome (25,000 genes) and the environmentally acquired human microbiome (over 1 million genes). The two genomes must work in harmonious integration as a hologenome to maintain health. Nutrition plays a crucial role in directly modulating our microbiomes and health phenotypes. Poorly balanced diets can turn the gut microbiome from a partner for health to a "pathogen" in chronic diseases, e.g. accumulating evidence supports the new hypothesis that obesity and related metabolic diseases develop because of low-grade, systemic and chronic inflammation induced by diet-disrupted gut microbiota. Due to the tight integration of gut microbiota into human global metabolism, molecular profiling of urine metabolites can provide a new window for reflecting physiological functions of gut microbiomes. Changes of gut microbiota and urine metabolites can thus be employed as new systems approaches for quantitative assessment and monitoring of health at the whole-body level with the advantage of measuring human health based on the results of interactions between the two genomes and the environment rather than just host genomic information. Large-scale population-based studies in conjunction with these whole-body level systems methods will generate pre-disease biomarkers with predictive power, thus making preventive health management of populations with rapidly changing disease spectrums possible through re-engineering of the imbalanced gut microbiomes with specially designed foods/diets.