“If we can confirm the existence of a similar pathway in humans, it may offer an effective way to increase people’s exercise levels to improve public health in general,” said study lead author Christoph Thaiss, Ph.D., professor of microbiology. at Penn Medicine.
Thais and colleagues set out to look broadly for factors that determine exercise performance. They recorded the genome sequence, gut bacterial species, bloodstream metabolites and other information for the genetically diverse mice. They then measured the amount of wheel the animals voluntarily ran on a daily basis, as well as their endurance.
The researchers analyzed this data using machine learning to look for attributes of the mice that could best explain large inter-individual differences in the animals’ running performance. They were surprised that genetics accounted for only a small part of these performance differences, while differences in gut bacterial populations appeared to be significantly more important. In fact, they observed that giving mice broad-spectrum antibiotics to rid them of gut bacteria nearly halved the mice’s ability to function.
Gut bacteria can improve exercise performance
Ultimately, in years of scientific detective work involving more than a dozen separate labs at Penn and elsewhere, the researchers found that two types of bacteria were closely associated with better performance. Eubacterium rectal and Coprococcus eutactus, producing metabolites known as fatty acid amides (FAAs). The latter stimulates receptors called CB1 endocannabinoid receptors on sensory nerves located in the gut that connect to the brain via the spinal cord. Stimulation of these CB1 receptor-coated nerves causes increased levels of the neurotransmitter dopamine in a region of the brain called the ventral striatum during exercise.
The striatum is a critical node in the brain’s reward and motivation network. The researchers concluded that extra dopamine in this region during exercise enhances performance by increasing the desire to exercise.
“This gut-to-brain motivational pathway may have evolved to prime the availability of food and the state of the gut bacterial population to engage in prolonged physical activity,” said study co-author J. Nicholas Betley, Ph.D. , Associate Professor of Biology, School of Arts and Sciences, University of Pennsylvania. “This line of research could lead to a whole new field of exercise physiology.”
The findings open up many new avenues of scientific inquiry. For example, there was evidence from experiments that better-performing mice experienced a more intense “runner’s high”—as measured by reduced pain sensitivity—suggesting that this well-known phenomenon is also at least partially controlled by the gut. bacteria. The team is now planning further studies to confirm the existence of this gut-to-brain pathway in humans.
In addition to offering inexpensive, safe, diet-based ways to get regular people into running and optimize the performance of elite athletes, he added, researching this pathway could also provide easier ways to change motivation and mood in conditions like addiction and depression.