It’s In Your Gut

America is an increasingly overweight country and the problem seems to be getting worse. Already over one-half of Americans are considered overweight and each year more and more people tip the scales into the overweight category. Many factors likely contribute to this trend, but ultimately if we consume more calories than we burn each day we slowly add pounds. Resolving to lose weight is a pretty typical New Years’ resolution although this good intention is often difficult to achieve. Trying to reduce calories and increase exercise sounds simple but finding the motivation and time to do either or both can be daunting. One factor in maintaining an exercise regimen is that physical activity can induce pleasurable neurochemical changes in the brain that motivate us to continue the activity, likely through compounds called endocannabinoids. Exercise increases the levels of endocannabinoids in the bloodstream and these molecules easily pass into the brain to reduce anxiety and produce a calming effect. However, how the production and regulation of endocannabinoids vary from individual to individual remains poorly understood. A new study in the journal Nature found that exercise motivation in mice can be linked to the production of endocannabinoids by their gut microbiome. It is not known if there are similar effects in humans, but this animal research is an intriguing finding that reveals new nuances in the gut-brain connection that might someday help humans exercise more.

The mouse study began with the observation that some mice were extremely active on their exercise wheels while other mice were the equivalent of human couch potatoes who rarely used the exercise wheel in their cages. Extensive testing revealed no significant differences in the genetics or biochemistry of the active mice versus the sedentary mice. A clue came with the observation that antibiotic treatment (which would disrupt the gut microbiome) reduced the exercise levels of the active mice. Examination of their brains revealed that levels of dopamine, a neurochemical that makes you feel good, also declined after antibiotic treatment. In the converse experiment, germ-free mice that have no gut bacteria were given the gut microbes from active mice. The introduction of these microbes caused the germ-free mice to exercise more and have higher dopamine levels, suggesting that the microbes were influencing this important neurochemical. In extensive additional studies, the authors were able to attribute the effect to two bacterial species known as Eubacterium rectale and Coprococcus eutactus. Both of these species in the gut produce chemicals called fatty acid amides (FAAs). FAAs released by these bacteria bind to the cannabinoid receptors on sensory nerves in the gut, essentially mimicking the action of endocannabinoids. FAA binding to these receptors ultimately causes dopamine levels in the brain to be increased during exercise. Removal of these bacteria eliminates the exercise-induced dopamine increase, and the exercise effect can be restored by simply exposing the gut sensory nerves to purified FAAs. These results establish a clear gut-brain connection where specific bacteria produce substances that contribute to a positive neurochemical response to exercise, an effect that likely promotes increased exercise by the mice harboring these bacteria.

At this time it is unknown whether or not a similar process exists in humans where specific gut bacteria would promote a greater feeling of well-being in response to exercise. Studies are in progress to examine this gut-brain connection in humans, and maybe soon we will see simple and effective new products to help with weight loss. It would be great if dietary supplements (like FAAs) or probiotics with specific bacteria could increase our activity levels and help us all be more inclined to seek out exercise with all its attendant benefits. In the meantime, I wish everyone happy holidays, a wonderful 2023, and a healthy microbiome.

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