Role of the gut microbiota in defining human health

Abstract

The human superorganism is a conglomerate of mammalian and microbial cells, with the latter estimated to outnumber the former by ten to one and the microbial genetic repertoire (microbiome) to be approximately 100-times greater than that of the human host. Given the ability of the immune response to rapidly counter infectious agents, it is striking that such a large density of microbes can exist in a state of synergy within the human host. This is particularly true of the distal gastrointestinal (GI) tract, which houses up to 1000 distinct bacterial species and an estimated excess of 1 x 10(14) microorganisms. An ever-increasing body of evidence implicates the GI microbiota in defining states of health and disease. Here, we review the literature in adult and pediatric GI microbiome studies, the emerging links between microbial community structure, function, infection and disease, and the approaches to manipulate this crucial ecosystem to improve host health.

Figure 1. Factors that influence the infant gut microbiome and early immune development

Exposure to farm animals and pets, vaginal birth and breast milk, all of which have a potential microbial link, are putatively associated with a beneficial effect on the developing gut microbiome and host immune response. Factors such as urbanization (lack of microbial exposures), formula-only diet and antibiotic administration during the neonatal stage are associated with the development of subsequent chronic diseases such as asthma and atopy, putatively through the development of aberrant gut microbiomes.

Figure 2. Consequences of immune system imbalances

Immune system homeostasis involves a regulated balance of inflammatory and anti-inflammatory cells; however, skewed responses putatively through lack of microbial exposure or outgrowth of pathogenic species may contribute to imbalances associated with the development of chronic inflammatory disorders.

Figure 3. Factors critical for successful probiotic, prebiotic and synbiotic trials

Consideration of interpersonal genetic and microbiome variations, standardized trials with defined outcomes and characterized strains coupled with high-resolution microbial phylogeny, microbiome functional profiles and host responses, are necessary to fully understand the potential impact of microbiome manipulation through probiotic, prebiotic or symbiotic supplementation.