The impact of the gut microbiota on human health: an integrative view

Abstract

The human gut harbors diverse microbes that play a fundamental role in the well-being of their host. The constituents of the microbiota--bacteria, viruses, and eukaryotes--have been shown to interact with one another and with the host immune system in ways that influence the development of disease. We review these interactions and suggest that a holistic approach to studying the microbiota that goes beyond characterization of community composition and encompasses dynamic interactions between all components of the microbiota and host tissue over time will be crucial for building predictive models for diagnosis and treatment of diseases linked to imbalances in our microbiota.

Figure 1. Development of the Microbiota

The gastrointestinal tract of the fetus is sterile until birth, after which the newborn is initially colonized. Depending on delivery mode, the initial communities tend toward a skin-like (caesarean section) or a vaginal-like (vaginal delivery) configuration. During the first weeks of life, there is a reduced activity of TLRs, potentially allowing the necessary formation of a stable bacterial community in the gut. As the infant grows, and with the introduction of solid foods, the microbiota diversity increases, and the community converges toward an adult-like state. At the same time, the immune system “learns” to differentiate between commensal and pathogenic bacteria. By adulthood, a relatively stable community composition (but varying between different individuals) is achieved, dominated mostly by Bacteroidetes and Firmicutes. Different diseases are characterized by significant changes in the microbiota and associated changes in the production of cytokines.

Figure 2. Effect of Interactions of Bacteria, Viruses, and Eukaryotes in Health and Disease

Diseases have been traditionally studied under a paradigm of “one microbe, one disease.” However, a new understanding is emerging on how disease phenotypes are actually a result of complex interactions between bacteria, viruses, and eukaryotes, as well as their interactions with the host or with certain drugs. Virulence of some eukaryotes is, for instance, linked to the presence of certain bacteria, such as in the case of E. histolytica and E. coli or S. dysenteriae. The susceptibility of the host to viral infections is conditioned by the particular configuration of the microbiota, whereas herpesvirus infection can confer resistance to certain bacterial infections. Antibiotics can significantly reshape the composition of the microbiota. As a clear correlation has been observed between many diseases and dysbiosis, the widespread use of antibiotics may be linked to the dramatic increase observed in autoimmune diseases over the last years. Conversely, helminthes confer resistance to autoimmune diseases.