The Human Microbiome: Implications of the Microcosm Within Us

Claire M. Fraser presenting at 2015 AAAS Annual Meeting Symposium, The Human Microbiome: Implications of theMicrocosm Within US. | AAAS/Christine A. Scheller

A thriving ecosystem exists in and on us, and it is made up of micro-organisms whose genetic material outnumbers human genes. What are the ethical and social implications of this ecosystem? How do we think about ourselves in light of it? How do the research techniques for studying these micro-organisms shape our perceptions of both the science and its meaning? These are a few of the questions addressed at a DoSER symposium, “The Human Microbiome: Implications of the Microcosm Within Us,” that was held at the AAAS Annual Meeting in February 2015.

Claire M. Fraser, Director of the Institute for Genome Sciences at the Maryland School of Medicine and a member of the AAAS Board of Directors, opened the discussion with an introduction to microbiome research.

We and our microbes have coevolved and this coevolution has created an ecosystem that mutually benefits both organism and host, said Fraser. “Our microbiome, particularly in the gut, contributes to the digestion of our food, provides energy for our metabolism, and makes a number of essential vitamins and other bioactive compounds,” she said.

“Every surface and cavity of the human body is colonized by these complex communities of organisms,” said Fraser. “We’re hosts to probably more than 100 trillion microbial cells, ten times the number of human cells. Calculating genome size and gene density, there are at least 100 times more genes than in the human genome.” And, she said, each of us seems to carry a unique microbial fingerprint. The microbiota across individuals is far more diverse than the diversity in the human genome across individuals.

Fraser studies the human gastrointestinal tract. As conditions along the GI track change, so do the numbers and types of microorganisms present there. Scientists are beginning to understand that this is a carefully orchestrated homeostasis.

Much of the initial research funded by the National Institutes of Health (NIH) Human Microbiome Project (HMP) has been focused on trying to understand what happens to these communities over the course of a human lifetime, Fraser said.

Early in life, the development of microbiome diversity is critically important for the maturation of the immune system, which learns to distinguish our microbial partners as “self” and not invaders. While the mature microbiome is relatively stable throughout adulthood, its diversity is susceptible to fluctuations and decreases as individuals get older, Fraser said.

One study compared the composition of gut microflora in young children in U.S. with those in less developed settings, she said. It found that there tends to be far less microbiota diversity in developed countries than in rural ones.

“Because high biodiversity can stabilize an ecosystem—allowing for resiliency and flexibility in responding to environmental changes—this issue raises the question: are we doing something in the developed world to influence the evolution of our microbiota in such a way as to drive it toward less diversity?” Processed foods, less interaction with nature, and overuse of both antibacterial products and antibiotics may contribute to low diversity, she said.

Both the HMP and the European MetaHIT projects have focused on potential changes in the microbiome associated with diseases like allergies and asthma, immune disease, obesity and other metabolic disorders, cognitive dysfunction and mental illness. The first five years of HMP looked for these associations, Fraser said. Comparing healthy and disrupted communities, dysbiosis (altered microbiota) emerges as a potential contributor to all of them. However, she cautioned that correlation with changes in microbiota is not the same as causation of disease, and said follow-up studies need to be done.

There are four possibilities for manipulating microbial populations to reverse dysbiosis: diet, prebiotics, probiotics, and fecal microbial transplants.

One of the most important factors in modulating composition and possibly function of microbiota, especially early in life is breast-feeding rather than formula feeding. A number of studies suggest that differences persist for the first few years of life, with the key factor being that some complexes in breast-milk feed specific microbes that live in human GI tracts. In adults, diet can rapidly and reproducibly alter the gut microbiome, with plant-based diets offering key beneficial organisms, but only while the diet is followed.

Probiotics “reseed” microbiota with beneficial microbes, whereas prebiotics are indigestible carbohydrates that as food for probiotics in the human body. Studies show the benefits of both, but there is still a lot of science to be done, Fraser said.

In some cases, when a pathogenic microorganism overtakes the normal gut flora, fecal microbiota transplants that use homogenized feces from a healthy fecal can be an effective treatment. For example, fecal transplants have been so successful in treating potentially fatal antibiotic resistant C-diff infections that clinical trials have been halted. With one fecal transplant, there is an 80% cure rate. A second transplant results in a 90% cure rate, she said.

“Thinking about health and or disease, we cannot ignore microbiota as an essential component,” Fraser concluded.

 

John Huss slide | AAAS/Christine A. Scheller

Nada Gligorov, Associate Professor of Medical Education and Associate Director of Bioethics Education at Icahn School of Medicine at Mount Sinai, spoke to the philosophical and ethical implications of HMP, focusing on how discoveries might influence how we think about ourselves and our identity.

HMP redefines our relationship with organisms that live in and on us from an adversarial to a more symbiotic conception. Instead of wanting to cleanse ourselves, we realize that in some cases these organisms can be beneficial and even essential to health, Gilgorov said. Each person’s unique microbiome can give a lot of information about that person regarding lifestyle (diet), personal habits (travel), past medical history (antibiotics), etc. In light of these facts, are microbes part of who we are?

Narrative identity captures a common sense notion of identity, and could be affected by HMP and its findings, she said. In answer to the question “Who are you?” or “Who am I?” this approach weaves together a story made up of memories, facts, and personal traits (preferences, morality).

We choose characteristics and values to highlight and others to ignore. So, although we might not think of our microbiome as an essential aspect of our being, if we broaden our conception of identity, we can begin to define ourselves by what we learn from scientific discoveries. This is similar to what has happened with neuroscience. The more we learn more about how our brain controls at least some of our psychological features, the more we integrate that information into our sense of self and others, she said.

We can also conceive of ourselves as the “biological we,” meaning we are at least in part the microbes that live within us. Philosophers Margaret P. Battin and Leslie P. Francis introduced the idea of the “way-station self” —we are both disease victims and carriers. “It’s not just that we carry them within us, but that microbes are passing through us, affecting other people. This could have impact on how we view our own autonomy,” said Gilgorov. 

Finally, Gilgorov noted that we tend to think of ourselves as having a barrier between us and our environments, but findings from HMP challenge this idea. If the environment lives on us and in us, and it affects us in tangible ways, this can affect how we think of our responsibilities to both environment and our own microbiome. For example, some people think of themselves as germaphobes. Learning that bacteria can be beneficial and even necessary could alter this self-perception.

University of Akron Philosopher of Science John Huss said the tools available for doing scientific research can end up influencing the terms we use to describe the world. For example, metagenomics is a set of tools used for analyzing the large quantities of genetic sequence in microbial communities. But there are linguistic consequences to this approach.

Huss sees two usage patterns of the word ‘microbiome” in the scientific literature. One refers to an ecosystem of microbes, which is an ecological conception; the other refers to the collective microbial genome, which is assimilated via systems biology. Although these conceptions are coalescing in scientific literature, people still conceive of the human microbiome differently.

Microbes on the human body are not easy to culture, so metagenomics is a way of taking samples directly from an environment to study them in bulk with high sensitivity, Huss said. Treating the metagenome itself as a genomic unit enables scientists to talk about it more easily. It also opens up ways of investigating whether it’s possible to sidestep individual species of microbes and view the metagenome from a holistic, systemic point of view. In this way, the language moves from technical capabilities to conceiving of the microbiome in a certain way.

Huss referenced the work of psychologist Gerd Gigerenzer in explaining that research tools may be driving the concepts we use to describe nature. He said this is important because it adds to the list of drivers of scientific research. “Before long we may think of operational units as natural units,” said Huss. “This reification can be helpful, but we need to step back and recognize the implications.”

Discussant Mildred Cho, Research Professor at Stanford Center for Biomedical Ethics, said scientists are often taught that science is a value-free, but “value-laden terms” like natural, normal, dysbiosis, and holistic that emerged in the discussion involve choices and judgments about values and culture. Microbiome scientists are involved in driving the implications of their research through the choices they make, said Cho.