Pew Scholars Study How the Gut Affects Our Motivation to Work Out

The human gut is home to trillions of bacteria that make up the intestinal microbiome, which is foundational to good digestion, a functional immune system, and a healthy brain. And now, according to recent research, this complex array of microbes might also play an important role in our motivation to exercise.

In a study published last year in the scientific journal Nature, Pew scholar Christoph Thaiss, Ph.D., looked to determine what biological mechanisms are behind why some people are more driven to exercise than others. In collaboration with fellow Pew scholars Maayan Levy, Ph.D., and Amber Alhadeff, Ph.D., Thaiss used cutting-edge technologies spanning the researchers’ shared expertise in microbiology, metabolism, and neuroscience.

Their findings pinpointed specific microbes that, when present in the gut, activated a mouse’s impulse to keep running. If these findings are applicable to the human microbiome, they could transform the way scientists (and the rest of us) understand and improve health through exercise.

This interview with the three scholars has been edited for length and clarity.

What motivated this study?

Courtesy of Christoph Thaiss, Ph.D.

Thaiss: Exercise is essentially the single most effective tool we humans have to protect us from many diseases. Yet several studies show that only a small minority of people worldwide achieve the World Health Organization’s recommendation of 150-300 minutes per week of moderate-intensity exercise. Busy schedules and rainy weather aside, we wondered: Why is that? What are the physiological mechanisms that regulate an individual’s capacity and motivation for exercise?

How did you conduct this study?

Thaiss: We assessed the exercise capacity of a large cohort of mice on treadmills and running wheels. And we observed that some mice were more driven to keep running than others. We then explored why this variability might exist, looking at genetics and metabolism, among other factors. To our surprise, intestinal microbes emerged as important regulators of exercise performance.

How so?

Thaiss: In a nutshell, we found that gut microbes drive the exercise-induced dopamine surge in the brain known as the “runner’s high” feeling. We confirmed this by administering antibiotics that killed these gut microbes, after which the mice ran for much shorter periods of time. 

How exactly does this relationship between gut microbes and the dopamine surge work?

Courtesy of Maayan Levy, Ph.D.

Levy: We observed that molecules released by bacteria in the gut—specifically, fatty acid amide metabolites—are associated with enhanced exercise performance. Metabolites are molecular byproducts that are produced during metabolism, a process through which we convert various substances, including food, into energy. We found that these fatty acid amide metabolites activate receptors that line the sensory nerves connecting the gut and the brain through the spinal cord. When these sensory nerves are activated during exercise, dopamine levels rise. This dopamine surge happens in the same brain region that influences motivated behavior and physical activity.

Can the findings from your research, which was conducted with mice, be applied to humans?

Thaiss: It’s too early to say for sure. However, the intestinal microbes that drive exercise performance in mice exist in the human gut as well, so it’s possible that exercise motivation in humans is driven in similar ways.

Levy: Metabolite-initiated pathways like this one are particularly attractive for turning into therapies because they are low cost, accessible, and minimally invasive. If human studies can confirm that this gut-brain pathway plays a role in regulating exercise motivation, it could open up a whole new branch of exercise physiology.

It’s great to see several Pew scholars work together on a study. How did your collaboration come together?

Thaiss: This was a really fun collaboration. My lab established a new platform to record mice with manipulated microbiomes. However, to understand how the microbiome influences exercise motivation, we needed experts who could manipulate neuronal gut-brain pathways and identify key metabolites. Amber Alhadeff and Maayan Levy’s labs were critical collaborators in this effort.

Dr. Alhadeff, what does your lab work on?

Courtesy of Amber Alhadeff, Ph.D.

Alhadeff: We’re interested in gut-brain signaling and its effects on food intake and weight control: We’re exploring how different foods impact neural activity in hunger centers within the brain and trying to understand the gut-brain pathways that mediate these effects. We’re also studying how to make obesity treatments more effective.

A good fit for a study on exercise!

Alhadeff: Exactly. My lab can manipulate gut-brain sensory nerve pathways. So, when the Thaiss lab discovered that the gut microbiome influences the motivation to exercise through altering dopamine signaling in the brain, they enlisted our help to understand how this happens. This collaboration was a fun opportunity for us to study something outside of the scope of my lab—the microbiome.

Dr. Levy, what is your lab exploring?

Levy: My lab’s mission is to identify metabolites as therapeutics for human disease. Metabolites play a powerful role in intercellular and inter-organ communication and have a profound impact on health and disease development. We specifically focus on metabolites that enter the human body from environmental sources, such as diet and the microbiome, to determine how they can be used for disease treatment.

So what did your lab bring to this study?

Levy: We were able to share the knowledge and technologies we use to study metabolites. We analyzed microbiomes and conducted in vitro experiments with microbiome-derived metabolites and performed metabolite supplementations in the exercising mice to try and pinpoint the effects of specific metabolites on motivation.

Any final thoughts?

Thaiss: This study exemplifies how the Pew scholars program helps us advance our science: We didn’t anticipate the many turns this project took and we didn’t have any traditional funding source to support the research, so the flexible support from Pew was instrumental in pursuing the study wherever the data led us. In addition, because the Pew network provides us with contacts and collaborators from many different fields of science, we were able to combine various technologies across disciplines to most effectively address our scientific questions.