In 2007, the Human Microbiome Project — an international effort to characterize the microbial communities found in the human body and to identify each microorganism’s role in health and disease — was launched. As a result of this effort, our understanding of the human microbiome expanded appreciably and, in the past few years, we’ve come to fully appreciate how beneficial our microbiome is to us. Made up of dynamic communities of trillion microbes, the microbiome consists of eukaryotes, archaea (primitive single-celled organisms), bacteria and viruses that reside on and in our bodies. These microbes complement each other and the human host, and play important roles in a variety of biological processes. Indeed, 0ur microbial partners carry out a number of metabolic reactions that, although not encoded in the human genome, are necessary for human health. Thus, the microbiome may represent a newly recognized organ, capable of a great variety of metabolic activities.
The microbes that make up the microbiome inhabit not just the gut and areas directly exposed to the outside world, but also parts of the body that were long assumed to be microbe-free, such as the placenta, which turns out to harbor bacteria most closely akin to those in the mouth. The mouth microbiome is also suspected of influencing bacterial communities in the lungs, the penis, the vagina, and the skin.
It is not surprising, then, that our current perception of human health is influenced by the increasing appreciation of the microbiome, resulting in the development of novel approaches for the prevention and treatment of different diseases. A recent study highlights the importance of the gut microbiome in promoting immunity to vaccination and provides an outstanding example of how understanding the microbiome can help in the prevention of infectious diseases.
The study (TLR5-Mediated Sensing of Gut Microbiota Is Necessary for Antibody Responses to Seasonal Influenza Vaccination) shows that antibiotic treatment given before or during vaccination may impair immune responses to vaccines by depleting the intestinal microbiome . Bali Pulendran, lead author of the study, said in a press release: “Our results suggest that the gut microbiome may be exerting a powerful effect on immunity to vaccination in humans, even immunity induced by a vaccine that is given at a distant site.”
In previous studies, Pulendran and his collaborators observed a strong correlation between high expression levels of the gene encoding Toll-like Receptor 5 (TLR5) and a strong antibody response to the influenza virus in vaccinated individuals. TLR5 encodes a protein that enables immune cells to sense flagellin, the main structural protein for the whips (flagella) many bacteria use to propel themselves. By interacting with TLR5, flagellin triggers the immune system to generate effective responses to infectious microbes.
The new study shows that the sensing of flagellin by cells of the immune system is a critical component affecting vaccine responses in mice. Mice treated with antibiotics and germ-free mice mount reduced immune responses to the flu vaccine when compared to mice with an intact microbiome. Mice still colonized with bacteria but lacking TLR5 exhibit reduced immune responses, similar to those observed in antibiotic-treated and germ-free mice. Oral reconstitution of antibiotic treated mice with bacteria containing flagellin, but not with mutant bacteria lacking flagellin, could restore the decreased antibody response.
Pulendran added: “These results demonstrate an important role for gut bacteria in shaping immunity to vaccination, and raise the possibility that the microbiome could be harnessed to modulate vaccine efficacy. The key question is the extent to which this impacts protective immunity in humans.”
Below is a fun overview of our microbiome (The invisible universe of the human microbiome) from National Public Radio!