Systems biology of the interactions between the gut microbiome and human metabolism

The three-way interaction between the gut microbiome, diet and host metabolism has a critical impact on human health with long-reaching effects. The microbiome is implicated in the aetiology or development of many diseases and is key to the status of the immune system. Co-evolution of host and microbiome has influenced the functionality of both the microbiome and host such that metabolic complementarity exists within the microbiota and that critical biosynthetic pathways are provided for the host that significantly extend host metabolic capacity. Environmental factors, particularly diet, can modulate the composition of the microbiome and various nutritional interventions have been investigated. High resolution spectroscopy together with multivariate mathematical modeling has been used to model the metabolic consequences of perturbing microbiota and to profile the effects of nutritional interventions on both the metabolism and the microbiome. Basic studies in germ-free and antibiotic-treated animals have shown stark changes in the urinary and faecal metabolomes, which are largely restored to ‘normal’ following recolonization. Recent research indicates that in both germ-free and antibiotic models of microbial depletion, the bile acid profiles of several tissues are significantly different from conventional animals, and contain a substantially higher percentage of tauro-conjugated bile acid species, indicating that the presence of microbiota influences the global metabolism of the host.The strength of microbial influence is also illustrated by studies showing that the in utero and early postnatal environments leave a metabolic imprint, which can last decades and may help in understanding the predisposition of preterm and low birth weight individuals to metabolic syndrome. Thus, the pre-and perinatal window provides great potential for nutritional intervention with the aim of improving long-term health.