Scientists discover species of gut microbes that may increase motivation to exercise
If the gut-to-brain pathway found in mice also exists in humans, it could be used as an effective method of enhancing exercise and promoting 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 at the University of Pennsylvania, certain types of gut bacteria can activate nerves in the gut to increase the drive to exercise. The study in mice identified a gut-to-brain pathway that explains how these bacteria can improve exercise performance.
The study found that variations in running performance among a group of laboratory mice were mainly due to the presence of specific intestinal bacterial species in the best-performing mice. The researchers identified that this effect is related to the small molecules called metabolites that these bacteria produce. These metabolites activate sensory nerves in the gut which, in turn, increase activity in a region of the brain that controls motivation during exercise.
“If we can confirm the presence of a similar pathway in humans, it could offer an effective way to increase people’s exercise levels to improve overall public health,” said study lead author Christoph Thaiss, Ph.D. ., Assistant Professor of Microbiology. in Penn Medicine.
Thaiss and his colleagues organized the study to look broadly at the factors that determine exercise performance. They recorded the genome sequences, gut bacteria species, bloodstream metabolites, and other data for genetically diverse mice. They then measured the amount of daily voluntary wheeling the animals did, as well as their stamina.
The researchers analyzed this data using machine learning, looking for attributes of the mice that might best explain the animals’ significant inter-individual differences in running performance. They were surprised to find that genetics seemed to explain only a small part of these performance differences, while differences in gut bacteria populations seemed to be substantially more important. In fact, they found that giving mice broad-spectrum antibiotics to get rid of their gut bacteria cut the mice’s running performance in half.
Ultimately, in a process of years of scientific research involving more than a dozen separate laboratories at Penn and elsewhere, the researchers found that two bacterial species were closely related to better performance, Eubacterium rectale Y Coprococcus eutactusproduce metabolites known as fats[{” 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.