Unlocking the Secrets of the Gut Microbiome

By Kendall Morgan
Electron micrograph of Exiguobacterium

Electron micrograph of Exiguobacterium

When it comes to our health, many of us probably still think of bacteria primarily as agents of infection or disease. But it’s now clear that the vast majority of bacteria living in and on our bodies aren’t doing us any harm. In fact, these microscopic organisms or “microbes” are essential in moderating our digestive and immune systems—perhaps even our mental health.

Efforts to catalog all those microbes, collectively known as the microbiome, have found that we each harbor about as many microbial cells as human cells, representing thousands of microbial species.

The diversity and many benefits of our microbial inhabitants have become abundantly clear, and yet scientists still know little about the molecular-level details of the relationship between humans or other animals and the microbes that inhabit them.

That’s in part because many of those microbial species are hard to grow in the lab. In the vast majority of cases, the tools to manipulate and study them at the molecular level don’t exist. As a result, detailed molecular study of most gut microbes has been considered “intractable.” That’s a fancy way of saying “hard if not impossible to do.”

But a study led by Professor Raphael Valdivia and Associate Professor John Rawls, both in Duke’s Department of Molecular Genetics and Microbiology and the Center for the Genomics of Microbial Systems, shows that there’s already a way.

“There are all kinds of wonderful activities bacteria perform,” Valdivia said. “They can kill other drug-resistant bacteria, break down toxins, and affect the absorption of drugs, for example. But we know little about how they achieve these things.

In Proceedings of the National Academy of Sciences recently, Valdivia, Rawls and their colleagues reported that they’ve developed a new approach to grab a microbe that does these amazing things and quickly find the genes responsible for their talents. The approach first uses a chemical to damage the microbes’ DNA. Next, the researchers look for microbes that develop new and interesting disabilities as a result of the exposure. They then sequence the genomes of microbes of interest to find the broken genes responsible for the loss.

As a first demonstration, the researchers applied their approach to identifying the genes required for one gut microbe’s swimming ability.

Valdivia and Rawls say they now plan to apply this new approach to other interesting traits and other bacteria in the human microbiome. For example, they’ve already started work on a species that others have proposed as a potential probiotic, protecting people on a high-fat diet from gaining weight.

“Over the last decade, we have learned that these microbes that normally inhabit our body surfaces can influence health in ways we had not previously imagined,” Rawls said. “From how we absorb and utilize dietary nutrients, to how susceptible we are to infectious disease and autoimmune disorders, or even how we respond to medicines, these microbes are key contributors to our overall well-being.”

Now, Rawls, Valdivia and others are poised to learn a lot more about how those microbial partners in humans and other animals do what they do and what that might mean for our health. Stay tuned.

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