Exercise has wide-ranging health benefits across the lifespan. Physical activity is a complex process that involves the musculoskeletal system as well as cardiovascular and respiratory factors. In addition to cardiovascular and respiratory fitness, another important factor required for competitive and recreational exercise is a strong motivational state. The sedentary lifestyle of humans enhances the risk of disease and there is great interindividual variability in exercise motivation and performance. However, the mechanisms that regulate the motivation for physical exercise of an individual are not well understood. Thaiss and colleagues report a gut–brain connection in mice that regulates the motivation for exercise, linking the intestinal microbiome to midbrain dopamine signalling.
But how does the microbiome influence exercise performance? The striatum is a brain region that is involved in motivated behaviour and the initiation of physical activity. The authors studied the potential role of the microbiome in the striatal response to exercise, and found that the level of striatal dopamine, which is a driver of physical activity, was increased after exercise, whereas this increase in exercise-induced dopamine levels was impaired following microbiome depletion. The data suggest that intestinal microbial colonization is required for the efficient release of dopamine following exercise. In agreement with this, activation of dopamine signalling restored exercise performance of antibiotic-treated mice. The authors went on to show that expression of the dopamine-degrading enzyme monoamine oxidase was decreased in exercising mice but not in microbiome-depleted mice, which suggests that the blunted dopamine response in the latter animals is due to monoamine oxidase-driven dopamine turnover. The effect of the microbiome on dopamine signalling required TRPV1-expressing gut-innervating sensory neurons. Importantly, the authors showed that microbiome-derived fatty acid amides (FAAs) promote exercise-induced neuronal activation. Germ-free mice colonized with an engineered Escherichia coli strain that contains genes of the biosynthetic gene cluster responsible for FAA biosynthesis exhibited enhanced running on both wheels and treadmills compared with control animals. Finally, stimulation of the endocannabinoid receptor CB1, which is expressed in TRPV1-expressing neurons, by FAAs drives sensory neuron activity, striatal dopamine release and enhances exercise performance.
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