New Year’s Resolutions are just around the corner. One of the most common resolutions is to exercise more and get in shape. However, this is also the one that many people tend to fail at. It can be hard to stay motivated to exercise enough to make it a habit, and until recently, we thought that the motivation to exercise came from a person’s genetics, learned experience, or pure discipline. I’m sure we all know someone in our lives who exercises religiously, and their motivation to engage in strenuous activity can sometimes be confounding. But what if they were getting some help from the bacteria in their gut?

Last week, a very interesting paper was published in the journal, Nature¹ (Figure 1). In this paper, they investigate the origins of the motivation to exercise. The motivation to exercise is important because we know that a sedentary lifestyle is associated with many serious and negative health consequences, from cardiometabolic disease to cognitive dysfunction and cancer². By understanding the science of motivation, we could improve people’s motivation to exercise, prevent the development of many diseases, and improve the outcomes of others.

Figure 1. New paper on exercise motivation

 

The authors of this paper set out to try and understand the motivation to exercise by trying to figure out why some mice exercised more than others. They looked at the genome, serum metabolome (compounds present in the blood), stool metagenome (bacteria and their genes present in the gut), and an assessment of metabolism and energy usage in mice at the same time as they measured the endurance capacity of the mice by forcing them to run on treadmills as well their voluntary running capacity, which they measured using the time that the mice spent on the wheels inside their cages every day (Figure 2). In fact, they collected more than 10,000 data points per mouse, and they used these data to build a model that could predict with good accuracy how far a mouse could run.

Figure 2. Experimental design

When they looked carefully at what factors were driving how well the model worked, they found that the microbiome composition was the biggest factor driving the mice’s ability to exercise! To confirm this, they treated mice with antibiotics, which wipe out the gut microbiome, and those mice performed worse in both the run to exhaustion and voluntary running tests. Furthermore, when they took the microbiome from one mouse and transplanted it into the other, the recipient mouse adopted the exercise patterns of the donor mouse (Figure 3).

Figure 3. Evidence for microbiome driving exercise motivation

 

These results confirm that the microbiome is intrinsically involved in how much we exercise, but how does this work? First, they identified a few species from a couple families of bacteria that were found in the mice that exercised more – Erysipelotrichaceae and Lachnospiraceae. These bacteria could improve the ability of the mice to run alone, without any other bacteria around. At first, they thought that these bacteria might be working in the mice by improving muscle function, but this was not the case. So, they started investigating the motivational state of the mice. During this line of research, they found that there is enhanced production of dopamine in the striatum (the region of the brain involved in motivated behavior and initiation of physical activity) in response to exercise in mice with a microbiome compared to those where the microbiome had been wiped out with antibiotics (Figure 4). This is important because dopamine is a neurotransmitter that is part of the brain’s reward system. It is one of the molecules in your body that make you feel good when you get a reward for something, so it makes sense that having more dopamine around when you exercise would make you want to exercise more.

Figure 4. The more dopamine is in the brain, the more the mice exercise

 

These are already important discoveries, but the authors didn’t stop here. They wanted to understand exactly how the bacteria could be increasing the concentration of dopamine in the brain during exercise. So, they investigated some known gut-brain connections, and they found that sensory neurons in the gut were being activated by a kind of molecule called an endocannabinoid. Endocannabinoids are molecules that interact with specific types of receptors in the nervous system, some of which are produced by gut bacteria. In fact, the two families that were identified as being important for exercise motivation actually contain the gene cluster for synthesizing fatty acid amides like N- oleoyl ethanolamide, one particularly effective type of endocannabinoid (Figure 5). When they put this gene cluster into a bacterial strain that did not have the ability to improve exercise performance, they observed the mice running more again. In this way, they were able to make the full connection between the gut bacteria, their metabolites, the sensors in the gut that interact with those molecules, changes in neurotransmitters in the brain, and a change in behavior - exercise!

Figure 5. The more N-oleoyl ethanolamide is in the gut, the more the mice exercise

 

So, what does this paper mean for you? This is the first paper that has really shown the close and vital relationship between the gut and the motivation to exercise. While previous papers like FitBiomics’ 2019 Nature Medicine Paper³ showed that the gut microbes can improve exercise performance through improving exercise physiology, this is the first-time exercise is considered a behavior that the gut microbes can control. While there are always a lot of caveats to studies in mice, thinking about exercise as a behavior we can change is more like how we as humans think about physical activity in real life.

Finally, while these results are exciting, it will probably be quite a few years until you will be able to buy a probiotic that will motivate them to exercise more. In the meantime, these families associated with exercise motivation in mice have also been associated with a healthy and diverse microbiome in general. By eating a varied diet rich in fiber, fruits, and veggies alongside taking a probiotic or eating fermented foods, this could be the year that you stay motivated to stick to an exercise related New Year’s Resolution!

Sources

1. Dohnalová, L., Lundgren, P., Carty, J.R.E. et al. A microbiome-dependent gut–brain pathway regulates motivation for exercise. Nature (2022). https://doi.org/10.1038/s41586-022-05525-z
2. Neufer, P.D., Bamman, M.M., Muoio, D.M. et al. Understanding the cellular and molecular mechanisms of physical activity=induced health genefits. Cell Metabolism (2015). https://doi.org/10.1016/j.cmet.2015.05.011
3. Scheiman, J., Luber, J.M., Chavkin, T.A. et al. Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nat Med 25, 1104–1109 (2019). https://doi.org/10.1038/s41591-019-0485-4

WRITTEN BY:  Marina Santiago, PhD

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