Scientists have discovered types of gut microbes that can boost motivation to exercise

Young man practicing stretching

If the gut-to-brain pathway found in mice also exists in humans, it could be used as an effective way to enhance exercise and promote better overall health.

Researchers have discovered a gut-to-brain pathway in mice that increases exercise performance.

According to a study published in natureLed by researchers at the Perelman School of Medicine University of PennsylvaniaCertain types of gut bacteria can activate nerves in the gut to increase motivation to exercise. The study in mice identified a pathway from the gut to the brain that explains how these bacteria can enhance exercise performance.

The study found that the differences in running performance among a group of lab mice resulted mainly from the presence of certain bacteria species in the gut of the better-performing mice. The researchers determined that this effect is related to small molecules called metabolites that these bacteria produce. These metabolites activate sensory nerves in the gut which in turn increase activity in the area of ​​the brain that controls motivation during exercise.

“If we can confirm that a similar pathway exists in humans, it could provide an effective way to boost people’s exercise levels to improve overall health,” said study senior author Christoph Theiss, PhD, assistant professor of microbiology. In Penn Medicine.

Theis and colleagues set up the study to look broadly at the factors that determine exercise performance. They sequenced the genomes, types of gut bacteria, bloodstream metabolites, and other data of genetically diverse mice. They then measured the amount of daily voluntary wheeling the animals ran, as well as their endurance.

The researchers analyzed this data using machine learning, looking for traits of the mice that could best explain the significant differences between the animals in running performance. They were surprised to find that genes seemed to account for only a small part of these differences in performance — while differences in gut bacteria populations seemed to be significantly more important. In fact, they observed that giving mice a broad-spectrum antibiotic to get rid of their gut bacteria reduced the mice’s running performance by nearly half.

Ultimately, in a years-long process of scientific investigative work involving more than a dozen separate laboratories in Pennsylvania and elsewhere, the researchers found that two types of bacteria were closely associated with better performance, Rectum Eubacterium And Coprococcus eutactusproduces metabolites known as liposomes[{” attribute=””>acid amides (FAAs). The latter stimulates receptors called CB1 endocannabinoid receptors on gut-embedded sensory nerves, which connect to the brain via the spine. The stimulation of these CB1 receptor-studded nerves causes an increase in levels of the neurotransmitter dopamine during exercise, in a brain region called the ventral striatum.

The striatum is a critical node in the brain’s reward and motivation network. The researchers concluded that the extra dopamine in this region during exercise boosts performance by reinforcing the desire to exercise.

“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,” said study co-author, J. Nicholas Betley, Ph.D., an associate professor of Biology at the University of Pennsylvania’s School of Arts and Sciences. “This line of research could develop into a whole new branch of exercise physiology.”

The findings open up many new avenues of scientific investigation. For example, there was evidence from the experiments that the better-performing mice experienced a more intense “runner’s high”—measured in this case by a reduction in pain sensitivity—hinting that this well-known phenomenon is also at least partly controlled by gut bacteria. The team now plans further studies to confirm the existence of this gut-to-brain pathway in humans.

Apart from possibly offering cheap, safe, diet-based ways of getting ordinary people running and optimizing elite athletes’ performance, he added, the exploration of this pathway might also yield easier methods for modifying motivation and mood in settings such as addiction and depression.

Reference: “A microbiome-dependent gut–brain pathway regulates motivation for exercise” by Lenka Dohnalová, Patrick Lundgren, Jamie R. E. Carty, Nitsan Goldstein, Sebastian L. Wenski, Pakjira Nanudorn, Sirinthra Thiengmag, Kuei-Pin Huang, Lev Litichevskiy, Hélène C. Descamps, Karthikeyani Chellappa, Ana Glassman, Susanne Kessler, Jihee Kim, Timothy O. Cox, Oxana Dmitrieva-Posocco, Andrea C. Wong, Erik L. Allman, Soumita Ghosh, Nitika Sharma, Kasturi Sengupta, Belinda Cornes, Nitai Dean, Gary A. Churchill, Tejvir S. Khurana, Mark A. Sellmyer, Garret A. FitzGerald, Andrew D. Patterson, Joseph A. Baur, Amber L. Alhadeff, Eric J. N. Helfrich, Maayan Levy, J. Nicholas Betley and Christoph A. Thaiss, 14 December 2022, Nature.
DOI: 10.1038/s41586-022-05525-z

The study was funded by the National Institutes of Health, the Pew Charitable Trust, the Edward Mallinckrodt, Jr. Foundation, the Agilent Early Career Professor Award, the Global Probiotics Council, the IDSA Foundation, the Thyssen Foundation, the Human Frontier Science Program, and Penn Medicine, including the Dean’s Innovation Fund.

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