Q&A: Unifying the microbiome sciences for global health and sustainability
Even if we can’t see them, microorganisms are everywhere, inextricably linked to life on Earth at every level. They range from pathogenic bacteria and viruses that can make us sick to the microbes that live in the digestive tracts of every animal, helping break down food for important nutrients, to soil microbes vital to our ability to grow crops and feed the world, and many, many more.
The community of microorganisms that inhabit a particular environment — which can include plants, animals, soils, oceans, the home and the gut — is known as a microbiome. Interest in the microbiome sciences has grown exponentially over the past few decades, tracing its recent roots to studies of microbial ecology just 20 years ago.
The Penn State One Health Microbiome Center, housed within the Huck Institutes for the Life Sciences, is today one of the largest and most active interdisciplinary collections of microbiome researchers, including over 550 members made up of Penn State faculty, postdocs, students and staff representing 42 departments in 10 colleges across Penn State and external partners. The center aims to foster long-term working relationships while simultaneously providing infrastructure and resources to support transformative, interdisciplinary microbiome research. Six months ago, the center received a prestigious international award for its global impact in microbiology and was visited by President Bendapudi, described in her “Note from Neeli: Penn State at the Forefront of Microbiome Research.”
Recently, members of the center from seven departments published an article in the American Society for Microbiology’s flagship journal, mBio, explaining how a “One Health framework” could unlock the full potential of microbiomes to enhance global health and sustainably manage ecosystems. In this Q&A, a few of the paper’s authors discussed how the center is leading the charge to breakdown traditional disciplinary silos and expand the One Health focus to include more than just pathogenic microbial threats.
Q: What is the One Health framework and how does it inform work at the center?
Seth Bordenstein, Dorothy Foehr Huck and J. Lloyd Huck Endowed Chair in Microbiome Sciences, director of the One Health Microbiome Center and professor of biology and entomology: The term “One Health” is fairly new, but the concept has been around for some time. It describes an approach to human health that incorporates our connections to agriculture and the environment. We wanted to use One Health as part of the name of our center to distinguish ourselves from the many other microbiome centers that have been established over the last 15 years, and as an indicator of our aspiration to unify and un-silo the microbiome sciences. The field has grown up very fragmented, with plant biologists trained in plant microbiomes, human scientists trained in human microbiomes, and so on. With the One Health Microbiome Center at Penn State, we make the argument that we study the microbiomes of everything and that there should be general rules, workforce development and education pipelines that extend across all these ecosystems, from agriculture to the environment to humans.
Q: Why does the One Health framework need to be expanded?
Bordenstein: Historically, One Health developed as its own distinct field, separate from the microbiome sciences. Importantly, it promotes a cross-disciplinary approach, but its focus has been on pathogens, such as the emergence of HIV from primates, or SARS-CoV-2 from bats. The time has come to upgrade that approach to include all microorganisms, and, most importantly, acknowledge the beneficial roles that microorganisms play in many aspects of our lives.
Nichole Ginnan, research project manager for the One Health Microbiome Center: I really hope that this expansion of the One Health framework can help us understand global health from a wellness and resilience perspective. Beyond looking at spillovers where pathogens move between different systems, like with COVID, we are interested in how other microbes, including potentially beneficial ones, move among “siloed” systems. If we can understand that we might be able to prevent disease and focus on wellness. We can use the framework to promote comparative and integrative studies across systems.
Erika Ganda, assistant professor of food animal microbiomes: As a veterinarian — especially when it comes to food production systems — we are focused on keeping our animals healthy so we can have a healthy food supply. Expanding One Health can help us to optimize animal health, production and the sustainability of our food supply.
Q: Why is it important to study microbiomes?
Ginnan: Originally, the microbiome was thought of more as a tool than as a discipline of its own. A plant scientist may have measured the microbiome to learn something about the particular plant they were interested in, but as the field has grown, we have realized the crucial role that microbes play in health across systems. We want to mature the microbiome sciences as its own discipline by developing foundational principles and theories. To do that, we must compare across systems so we can start to uncover the common rules and processes.
Bordenstein: Looking at the roots of microbiology and the germ theory of disease, microbes were originally thought of only as disease agents. In the last couple of decades, the microbiome sciences shined a light on the fact that maybe only 1% of human microbes are harmful to us and other animals, the other 99% are helpful or harmless. So, if we are going to solve long term problems in health and sustainability in any ecosystem — our bodies, agricultural output or the environment — we can’t just focus on pathogens, we need to broaden the view to include all microbes. Penn State is defining this future in the perspective piece and center operations.
Q: What are some examples of microbiomes, beyond our gut?
Bordenstein: Every environment that you can think of — our gut, plant roots, built environments, soil, amphibian skin — universally will have a microbiome defined by a community of microscopic organisms. The microbiome revolution has been defined by profiling the diversity of microorganisms in these communities. The call to action around One Health microbiome sciences is that we are only going to understand the health of the system by knowing not only what is there in that environment, but also how microbes flow through those environments to shape the risk of health and disease.
Ganda: Think about all the leaves that fall on the ground every autumn. If it wasn’t for the ecosystem services provided by the microorganisms that live on the leaves and in the soil, we would be swimming in leaves. Microbes are the ultimate recyclers.
Ginnan: Right, the soil is full of microbes. It’s estimated that 50% of the total biodiversity on Earth lives in the soil. So as a plant and soil microbiome researcher, I want people to think more broadly about microbiomes. They are all around us and impact our lives as the microbes move among environments, from soil to plants and animals and back.
Q: What does the shift in focus from pathogens to a broader idea of wellness mean for the microbiome sciences?
Bordenstein: We can think about fighting a pathogen with an antibiotic or an antiviral, we think about disease surveillance and trying to get at those problems early, but the idea that we could structure a microbiome in an environment or our bodies to prevent the disease is now front and center for the microbiome sciences and its part of this framework of what the field will do differently. We have many researchers here at Penn State who are thinking about these crucial issues for diverse systems. The idea is that we can understand a microbial community and how it is susceptible or resistant to a pathogen or chronic disease, then we can boil down that community to the essential ingredients that prevent the infection or illness. Engineering a synthetic microbiome to put back into the environment will prevent disease and also show us how microbiomes can enhance health and well-being naturally.
Ginnan: Engineering microbiomes is one approach, but in the agricultural sciences a lot of what we focus on is managing microbiomes. We think about microbiomes as a way to enhance resilience. Modern farming tends to rely heavily on synthetic fertilizers, which can disrupt natural plant-microbe interactions by reducing the plant’s dependence on microbial partners that cycle nutrients in the soil. Over time, this can lead to a decline in key microbial populations that play critical roles in supporting plant health, resilience to environmental stress, and nutrient acquisition. If synthetic fertilizers become too expensive, or during periods of environmental stress like drought, plants may be left without access to these beneficial microbes. In addition to or instead of inoculating engineered microbiomes, we aim to develop and implement management practices, like cover cropping, or adding specific soil amendments to enhance soil microbial diversity and promote microbial functions critical for plant health and resilience.
Ganda: For cows and other ruminants, for example, animal nutrition is dependent on stewarding the microbes that live in their guts. You might ask how cows can gain weight while just eating grass, while humans are told to eat leaves when we want to lose weight. This is because the microbes in the cows allow them to harvest energy from grass, and we don’t have most of those microbes. This “superpower” allows ruminants to harvest energy unavailable to humans and transform it into nutritious meat and milk which are important components of most human diets. So, there is a direct relationship between cow’s microbiomes and human nutrition.
Q: How can the connections between microbiomes at various scales — individual, population, environmental — be leveraged to increase global well-being?
Ginnan: No system on Earth is isolated, but we have historically studied them as if they were. We want to identify broad principles to understand how different microbiomes may act the same. One way to address that is to see how different microbiomes respond to stress. Do we see patterns of the same microbes, or genes that they express, becoming more abundant as a response to stress? This can lead us to uncover whether there are basic rules that microbial communities share. We’ve developed a whole range of basic theories of ecology and evolution for macroorganisms, do those same principles hold for microbes? In some cases, they will, and in some, they won’t, but if we can understand those patterns, we can move to managing microbial communities to support global health.
Q: Are there challenges to applying the One Health framework for microbiome sciences?
Bordenstein: One of the big challenges is that funding agencies are structured in a way that makes them not well poised to capitalize on the convergence theme crucial for interdisciplinary research. Of the three big agencies, the U.S. National Science Foundation is focused on basic science, the National Institutes of Health (NIH) on human science and the U.S. Department of Agriculture (USDA) on agricultural science. One Health microbiome science is trying to bring all of that together. So, the call to action in our paper is how do we restructure our research enterprise to address these broader questions that require a wider lens.
Q: How is Penn State and the One Health Microbiome Center facilitating the kinds of changes you are talking about?
Ginnan: Penn State is very supportive of interdisciplinary research and at the center we are working to do this through team science. We want interdisciplinary groups working together from the beginning, when they are just developing questions to guide their research.
Bordenstein: We are the only One Health Microbiome Center in the world and we’ve gotten recognition because of that. Penn State made a decision about 10 or 15 years ago to invest in the microbiome sciences by hiring exceptional early career researchers and that investment is paying off in the creative interdisciplinary research that we do today and for many decades to come.
One specific example of this is our collaboration with the Center for Reproductive Biology and Health, also housed within the Huck Institutes, to develop the first USDA graduate student training grant in animal reproductive microbiomes. We have another NIH training grant in review that sets up a universal curriculum for graduate students to learn the microbiome sciences, whether they study plants, animals or soil. We also have a dual title degree program, the first of its kind in the microbiome sciences, where we have a selection of 40 courses that students can take so that they could get, for example, a doctoral degree in biology and the microbiome sciences.
Ganda: The dual-title degree program came about at a faculty retreat, when faculty from different areas realized that we teach our students many of the same basic courses separately. Instead of each of us reinventing the wheel in our own silos, we could pool resources to ensure that students learned these foundational concepts. In addition, Penn State has the resources and facilities needed to do this type of research and the people are willing to collaborate and share information, which sadly, is not always the case.
In addition to Bordenstein, Ginnan and Ganda, the paper’s authors include Sharifa G. Crandall, assistant professor of soilborne disease dynamics and management; Madangchanok Imchen, postdoctoral researcher in biology; Francisco Dini-Andreote, assistant professor of phytobiomes; Tim I. Miyashiro, associate professor of biochemistry and molecular biology; and Vishal Singh, assistant professor of nutritional physiology and microbiome. The work was in part supported by resources of the One Health Microbiome Center.