Scientists at the University of Pennsylvania’s Perelman School of Medicine conducted a study in mice showing that some species of gut-dwelling bacteria trigger nerves in the stomach to boost the urge to exercise.

The study, which was just published in Nature, explains the gut-to-brain mechanism by which particular bacteria improve exercise ability.

The study concluded that the presence of certain gut bacterial species accounted for most of the variation in running ability across a large sample of lab mice.

Metabolites, tiny compounds produced by the bacteria, were shown to be responsible for this impact. These metabolites activate sensory neurons in the stomach, which in turn increases activity in a brain area that regulates motivation when exercising.

“If we can confirm the presence of a similar pathway in humans, it could offer an effective way to boost people’s levels of exercise to improve public health generally,” adds study senior author Christoph Thaiss.

Thaiss and coworkers designed the research to investigate a wide range of potential variables influencing physical performance. They collected information on genetically varied mice’s genomic sequences, gut bacterial species, bloodstream metabolites, and other factors.

Then, they measured how much the animals ran their wheels on their own every day and how strong they were.

Using machine learning, the researchers combed through these numbers in search of mouse characteristics that may account for the large variations in the mice’s running speeds.

The researchers were surprised to find that genetic factors accounted for only a small portion of the performance differences observed in the study, and that differences in gut bacterial populations were significantly more important.

In fact, scientists found that cutting mice’s gut flora out by administering broad-spectrum antibiotics cut the mice’s running capacity in half.

In the end, after years of scientific detective work in more than a dozen Penn and other labs, the researchers found that two bacterial species, Eubacterium rectale and Coprococcus eutactus, that are closely linked to better performance make metabolites called fatty acid amides (FAAs).

CB1 endocannabinoid receptors, which are located on gut-embedded sensory nerves, are stimulated by the latter. These receptors then connect to the brain via the spine

During physical activity, dopamine levels in the ventral striatum of the brain rise as a result of stimulation of these CB1 receptor-rich neurons.

In the reward and motivation network of the brain, the striatum plays a crucial role. The researchers came to the conclusion that the increased dopamine during exercise reinforces the desire to exercise, which improves performance.

“This gut-to-brain motivation pathway might have evolved to connect nutrient availability and the state of the gut bacterial population to the readiness to engage in prolonged physical activity,” adds study co-author, J. Nicholas Betley. “This line of research could develop into a whole new branch of exercise physiology.”

These findings have opened up many new avenues of scientific investigation.

Experiments revealed, for instance, that mice with superior performance had a more intense “runner’s high” as evaluated by a decrease in pain sensitivity, suggesting that this well-known phenomenon is also at least partially regulated by gut flora.

The team will now do more research to see if this gut-to-brain pathway is also present in humans.

He also said that studying this pathway could lead to cheaper, safer ways to get regular people to run and improve the performance of elite athletes. It could also make it easier to change motivation and mood in situations like addiction and depression.

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