In the first episode of our series, we looked at the cholera epidemic and how public health emerged as a corollary to the germ theory of disease. In this final episode, we arrive at what may be the next frontier in public health research, and once again we are chasing microbes.
Public health and medical research occasionally take unexpected turns that allow us to glimpse new wonders into the world we inhabit. After the scientific community had accepted Pasteur’s germ theory of disease, discoveries in microbiology increased exponentially, including Robert Koch’s use of agar in 1876 as a culture medium to isolate specific micro-organisms. This technique made possible an entirely new and exciting era of public health and medicine—vaccines, the adoption of aseptic techniques, and discovery of antibiotics have since saved millions of lives. Fast forward another century or so to the development of ‘omics technology, and we find ourselves yet again stunned and humbled by the complexity and vastness of the natural world, and handed a new direction for research in both new therapies and in public health—the microbiome
Beyond Traditional Microbiology
The microbiome—the complex community of commensal, symbiotic and even pathogenic microorganisms that inhabit all of us—is an entirely new frontier for the prevention and control of illness. Although public health and infectious disease research must continue to focus on immunity/ infection at the individual level, and the transmission of organisms at the population level—as Ebola recently illustrated—research into the microbiome is quickly moving us beyond traditional microbiology. Just as in the 1800s, when the discovery and use of vaccines prevented illness and death from diseases thought to be caused by miasma, the investigation of the “microverse” may ultimately result in prevention of illnesses that are not currently associated with microbes. For instance, cardiovascular disease is still the leading cause of morbidity and mortality in the US, and research has already implicated the gut microbiome in obesity, diabetes, cholesterol accumulation in the blood vessels, and other processes leading to arteriosclerosis5.
Thanks to the National Institutes of Health (NIH) Human Microbiome Project (HMP)1, we now have a handle on what the normal, healthy, microbiome looks like, and can begin to study how changes and variations in the microbiome are associated with illness in both individuals and populations.
Launched in 2008, the HMP consists of a community of researchers who purified and then analyzed 5,000 biological samples of human and microbial DNA using next-gen sequencing technology. They then sorted through 3.5 terabases of data to identify the genetic signals unique to bacteria, specifically ribosomal RNA 16S rRNA which identifies different microbial species. In 2012, the Director of the NIH, Francis Collins, announced that HMP researchers had identified between 81 and 99 percent of the genera that comprise the human microbiome, and also calculated that more than 10,000 species of microbes are represented.
The Alien Within / Without
The microbiome is possibly more in control of our physical state than we (i.e., our immune systems) are in control of them. We are all under the influence of alien life forms to a greater extent than we think. Some noteworthy observations regarding the microbiome:
- The typical human body hosts 10 times more microbial cells than its own cells, although an individual’s entire microbiome accounts for, at most, one to three percent of the body’s weight.1
- The human genome consists of some 22,000 protein-coding genes, while researchers at the Human Microbiome Project estimate that the microbiome has about eight million—360 times more—protein-coding genes! It is estimated that less than 10 percent of the DNA in the human body is actually human DNA.2
- Researchers at the European Molecular Biology Laboratory in Heidelberg, Germany, analyzed the meta-genomes of individuals from four countries, and found three distinct types of communities3 that transcend our nationality, ethnic origin, age, gender, and environment.
- A study by Lax, et al4 showed that we swap and share our microbiome with our environment and those we live with.
What are these organisms? We know quite a few of the species that are present, but the vast majority can be identified only by genera, and “only” at a community level. Even so, identifying the microbiome at the Genera level was a remarkable feat.
Biobanking Solutions for Microbiome-Related Research
This brings us back to the world of biobanking. We are only beginning to address the challenge of collecting, processing, and storing the samples needed to support research related to the microbiome. At the present time, we are limited by our lack of skills or media to culture these communities. Of those we can culture, the more adaptable organisms crowd out the less-adaptable or slower-growing ones so that an accurate picture of the community as a whole continues to elude us.
Those of us who support biomedical research by providing biological sample management have work to do. Best practices, standard operating procedures, clinical supplies, and other processes must be defined. The data appended to the samples must also be carefully considered. For example, the composition of the skin microbiome varies not only with location on the body, but between the surface of the skin and the depth of the dermis, so the collection of biospecimens using swabs vs. biopsies yields very different populations; the collection instrument, location of the body and tissue, and many other factors must be documented and annotated to microbiome-related samples.
It is time for prospective studies that will allow researchers to investigate the variations in microbial communities, both between individuals and over time within individuals, and the association of these variations with illness. From such studies can come preventive measures—perhaps a new category of vaccine corresponding to a new understanding of host-microbe interactions.
We wrap up this blog series with the realization that we are standing on the shore of a relatively unexplored new ocean of public health. We have an exciting future ahead of us.
We recently published an eBook on Controlling Preanalytical Variability in Biospecimen Collections. This is an issue that must be thoroughly addressed in public health research – the possibility that the handling of specimens prior to lab testing has skewed results. To read more, download our eBook below.
 The NIH Human Microbiome Project Website: http://hmpdacc.org/
 Human Microbiome Project Consortium. (2014). Structure, function diversity of the healthy human microbiome. Nature, 486, pp. 207–214.
 Arumugam, M.; & Raes, J.; Pelletier, E.; Le Paslier, D. & Yamada, T. et al. (2010). Enterotypes of the human gut microbiome. Nature, 473, pp. 174–180.
 Lax, S.; Smith, D. P.; Hampton-Marcell, J.; Owens, S. M. & Handley, K. M., et al. (2014). Longitudinal analysis of microbial interaction between humans and the indoor environment. Science, 345, pp. 1048–1052. doi:10.1126/science.1254529
 Tang, W.H & Hazen, S.L. (2014). The contributory role of gut microbiota in cardiovascular disease. Journal of Clinical Investigation, 124, pp. 4204–4211.