Dining in with Trillions of Fascinating Friends: Exploring Our Human Gut Microbiome in Health and Disease

摘要

Our genetic landscape is a summation of the genes embedded in our human genome and in the genomes of our microbial symbionts (the microbiome). Similarly, our metabolic features (metabotypes) are an amalgamation of human and microbial traits. Therefore, understanding of the range of human genetic and metabolic diversity means that we must characterize our microbiomes, which contain at least several hundred-fold more genes than our human genome, as well as the factors that influence the properties of our microbial communities (microbiota). The results should provide an additional perspective about contemporary human biology as we assess how our changing lifestyles, cultural norms, socioeconomic status, and biosphere are influencing our microbial ecology and health status. I will discuss the results of our group's ongoing metagenomic studies of the interrelationships between diet and the structure and dynamic operations of the human gut microbiome. We believe that understanding these interrelationships is important for advancing our appreciation of the nutritional value of food ingredients, for creating new nutritional guidelines for humans at various stages of their lifespan, and for developing new ways to deliberately manipulate the properties of the gut microbiota to prevent or treat various diseases. We have developed a translational medicine pipeline that involves metagenomic analyses of the gut microbial communities of adult mono- and dizygotic twins living in the USA who are lean, or concordant or discordant for obesity, and twins aged 0–3 years living in developing countries who develop normally, or who become malnourished and are treated with a ready-to-use therapeutic food (RUTF). Intact fecal communities from these individuals, or ‘personal’ culture collections that capture the majority of bacterial diversity in their microbiota, are then transplanted into germ-free mice, which are fed the diets of the human donors, or systematically manipulated derivatives of these diets. The impact of diet and microbiota on these humanized mice, including the degree to which the human donor's physiologic/metabolic phenotypes can be transmitted to gnotobiotic animals via microbiota transplants, are then studied using a variety of methods.