Blazing a microbiome path

Friday, November 1, 2019

Initiative puts OSU in the forefront of a complex emerging field

Over the last 20 years, microbiome research has been gaining more attention in the scientific community. Over the next 10 years, Oklahoma State University expects to become a national leader in the discipline, thanks to the Microbiome Initiative.

“Microbiome” refers to the community of bacteria, fungi, protozoa and viruses that inhabit a particular environment. They exist in places you might expect, such as your gut, and places you might not, such as clouds. The global microbiome includes millions of species, covering all animals, plants and physical environments on the planet. It can impact every aspect of Earth’s ecosystem, including human, animal and plant health.

Microbiome science is complex because of the interactions of interconnected communities of organisms and their hosts or other microbial communities in food, water or the created environment. Though still in its infancy, microbiome science already dominates thinking in the life sciences.

That is why OSU has designated the Microbiome Initiative as one of the university’s four Tier 1 Research Initiatives.

The Microbiome Initiative aims to provide researchers across the university with tools to produce innovative, consistent and reproducible research that determines cause and effect. Those tools include access to experts about each area of the process, from securing samples to producing computer models that predict the effect of adjusting variables. Together, the expertise and appropriate facilities will create a pipeline to take an experiment from hypothesis to reliable results.

“OSU is positioned really well to become a leader in microbiome research,” said Dr. Tyrrell Conway, one of the project’s four leaders and head of the Department of Microbiology and Molecular Genetics in OSU’s College of Arts and Sciences. “If you are a life science researcher of any kind, you are thinking about the microbiome. If you don’t have the capacity in your laboratory to test some of these things, you wish you did. That’s what the toolkit is for.”

Joining Conway as the project’s leaders are three other researchers, each from different colleges:

• Dr. Gerwald Koehler is a microbiology professor in the Department of Biochemistry and Microbiology at the Center for Health Sciences in Tulsa.
• Dr. Jerry Malayer is the College of Veterinary Medicine’s associate dean for research and graduate education and professor in the Physiological Sciences Department.
• Dr. Brenda Smith is a Regents Professor in the Department of Nutritional Sciences in the College of Human Sciences, as well as an associate dean of the Graduate College.

With them so far are 29 collaborators across OSU, including representatives from the College of Agricultural Sciences and Natural Resources; the College of Engineering, Architecture and Technology; and the College of Education, Health and Aviation.

“This is a great opportunity to have collaborative research across OSU,” Koehler said. “It’s going to lead to more interdisciplinary research. My vision is toward engaging more clinicians and social scientists in microbiome research.”

Conway is excited about microbiology receiving increased attention from the public. Early in his career, he would tell people he was a biologist because most people didn’t understand what a microbiologist was. Now he proudly says he is a microbiologist because most people know the term, and many either know about microbiomes, or at least have some idea about the concept.

For example, they know antibiotics can lead to complications such as digestive issues or yeast infections.

“The interest in microbiomes is a movement,” Conway said. “Microbiologists have known for many decades that microbes live in communities. But now lots of people who aren’t microbiologists are doing things like taking prebiotics to feed bacteria, stimulating growth. They are taking probiotics to introduce microbes that are beneficial. They are beginning to get that we are a cloud of our microbiomes.”

Over the past decade, Koehler has increasingly focused his research on microbiomes, especially on their interactions with host physiology and the gut-brain axis. For example, is there a connection between the composition of someone’s microbiome and whether they have severe depression or anxiety?

“We see changes that correlate in humans and our model systems,” Koehler said. “We see changes that correlate with depressive-like behavior in animals and major depression in humans. The question is, how do we get from correlations to mechanisms? We need to find out if depression causes changes in the microbiome, or do the microbiome changes cause depression?”

He is also excited about research into how the microbiome relates to neurodegenerative diseases such as Parkinson’s disease and gastroenterological issues such as inflammatory bowel disease. It may even play a part in causing cancer.

“Microbiome science is a great opportunity to learn things that we didn’t even know that we didn’t know,” Koehler said. “There are so many areas where people haven’t even considered the trillions of microorganisms within us and on us. When you get a physical now, they check your blood. In a couple of years, we might also get our microbiome checked to see if there is anything wrong with that.”

While Koehler studies the gut-brain axis, Smith’s expertise is the gut-bone axis. She notes that bones are greatly affected by a body’s immune response, and at any given time about 70 percent of a body’s immune cells reside within the gut. The saying “you are what you eat” makes a lot of sense as it relates to the microbiome.

“What we consume affects the microbiome, and in turn the immune cells, which can then travel into the bone and other tissues,” Smith said. “What we’ve learned in even the last decade about the microbiome is going to change the way we do nutrition.”

Today, nutritional recommendations are typically based on an individual’s age or gender, and whether a woman is pregnant or lactating. With an increased understanding of the microbiome, a much more individualized approach to these nutrition recommendations may soon be the norm.

“This is a paradigm shift,” Smith said. “It’s changing the way we think in nutrition and its effects on health.”

For example, there are some compounds in foods, such as resveratrol in red wine and catechins in green tea, that are known to have health benefits. Yet studies have shown they are poorly absorbed or have very short stays in the body.

“If we consider that the microbiome may be the target of their action, it may not be that I drink green tea and the beneficial compounds end up in some peripheral tissue,” Smith said. “We are beginning to think that the effect is primarily taking place in the gut, and as the microbes metabolize these compounds they influence the immune system.”

For Malayer, the idea of the global microbiome is “almost perfect.”

“We talk about one health — the concept that the health of animals, humans and the environment are linked,” Malayer says. “In research, the things we find in one environment can apply to another. At a basic level, processes of tissues, cells and organs are similar across species.”

The goal of microbiome science is to understand the microbiome. That includes which microbes are present, what they are doing and how they are interacting. That leads to research questions about the effects of eliminating certain classes of organisms, allowing other classes to expand.

“We’re talking about millions of bacteria, millions and millions of genes they are expressing, and millions and millions and millions of metabolites,” Malayer said. “That’s a very complex system. With the new technologies of artificial intelligence machine learning and supercomputers, we think we can program a computer to model that at some scale. That will let us do predictive analysis. ‘What would happen if you eliminate an organism? What would happen if you introduced a probiotic or prebiotic?’”

OSU has tremendous resources for multidisciplinary microbiome research. It is a comprehensive, land-grant university that includes both a medical school and a veterinary medical school, as well as extension offices that can share findings throughout the state.

Through the Microbiome Initiative, Malayer says OSU is empowering researchers to “plug into a pipeline” of expertise and specialized equipment that will allow them to “build your model without having to reinvent the wheel.” They will even train students, “who will become the next generation of scientists, and they will be doing a lot more of this kind of work.”

He added, “There is all kinds of potential to discover new processes and organisms in these various environments that could have commercial potential. The sky is the limit if we get everything in place. There are institutions that do things like this now, but I don’t think any other institution has the breadth of potential application that OSU does.”