Gut Microbiota and Exercise: When Performance Begins in the Gut….

In the last 10 years, exerkines have been explored as exercise mimetics for the treatment of different metabolic and cardiovascular diseases. We identified exerkines released from skeletal muscle, heart, liver, adipose tissue, brain, and gut, such as FGF21, IL-6, and adiponectin whose potential in the therapeutic field has been well consolidated. Is that all? Apparently not…

Recent advances in metagenomics led to a new class of bioactive molecule from the gut microbiota, determining the success of exercise in diabetes prevention, cardiac protection, and final performance. 

Professional athletes exhibit much higher gut microbial diversity than sedentary subjects, characterized by increased nutrient metabolism, and SCFA release. These microbes also utilize a lot of endogenous compounds such as bile acids, amino acids, and lactate.

They act as “hidden” molecular transducers of exercise, opening new scenarios in the development of edible exercise mimetics for improving performance and cardiometabolic health (as prebiotics and/or probiotics), as evidenced in several clinical studies [1]

Exercise elicits structural and functional changes in gut microbiota, with altered abundance of Proteobacteria, Firmicutes, Bacteroidetes, B. uniformis and Veillonella and higher microbial fermentation of carbohydrates with increased SCFAs and reduced BCAA. All, in turn, improves insulin sensitivity and glycemic homeostasis. In particular:

1.  Veillonella atypica contributes to elevated production of SCFAs by metabolizing skeletal muscle-derived lactate into propionate, leading to increased energy supply from gluconeogenesis and enhanced aerobic exercise capacity [2]

2. Eubacterium rectale and Coprococcus eutactus promote the production of fatty acid amides (OEA or oleoylethanolamide) under exercise stimulus. OEA, in turn, stimulates sensory neuron activity leading to improved motivation, dopamine-mediated, and exercise performance [3].

3. Allobaculum increases the production of 3-HPA (3- hydroxyphenylacetic acid), and 4-HBA (4-hydroxybenzoic acid) mediated by exercise, eliciting protection against myocardial infarction-induced heart failure [4].

Gut microbiota not only influences exercise performance but also controls individual responses, directing the cardiometabolic effects of exercise. 

Should exercise be tailored as much as nutrition? May individual responsiveness to exercise intervention be predicted by a machine-learning algorithm integrating gut microbiome with circulating exerkines profile and host physiology? How far are we from that? 🚀 ⏱ 

Link to the paper: https://doi.org/10.1038/s44321-024-00027-z

References

[1] Wang, K., Mehta, R. S., Ma, W., Nguyen, L. H., Wang, D. D., Ghazi, A. R., Yan, Y., Al-Shaar, L., Wang, Y., Hang, D., Fu, B. C., Ogino, S., Rimm, E. B., Hu, F. B., Carmody, R. N., Garrett, W. S., Sun, Q., Chan, A. T., Huttenhower, C., & Song, M. (2023). The gut microbiome modifies the associations of short- and long-term physical activity with body weight changes. Microbiome, 11(1), 121. https://doi.org/10.1186/s40168-023-01542-w

[2] Scheiman, J., Luber, J. M., Chavkin, T. A., MacDonald, T., Tung, A., Pham, L. D., Lee, A. J., Kostic, A. D., & Wolan, D. W. (2019). Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nat Med, 25, 1104–1109. https://doi.org/10.1038/s41591-019-0485-4

[3] Dohnalová, L., Lundgren, P., Carty, J. R. E., Estaki, M., Clarke, D. J. B., Cumming, R. C., & Knight, R. (2022). A microbiome-dependent gut–brain pathway regulates motivation for exercise. Nature, 612, 739–747. https://doi.org/10.1038/s41586-022-05525-z

[4] Zhou, Q., Deng, J., Pan, X., Tang, L., Chen, J., Xu, S., Zhang, Y., & Wang, Y. (2022). Gut microbiome mediates the protective effects of exercise after myocardial infarction. Microbiome, 10, 82. https://doi.org/10.1186/s40168-022-01271-6

[5] Jin, L., Diaz-Canestro, C., Wang, Y., Tse, M. A., & Xu, A. (2024). Exerkines and cardiometabolic benefits of exercise: from bench to clinic. EMBO Molecular Medicine, 1-13. https://doi.org/10.1038/s44321-024-00027-z