MassIVE MSV000091494

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A microbiome-dependent gut brain pathway regulates motivation for exercise

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Description

Exercise exerts a wide range of beneficial effects for healthy physiology. However, the mechanisms regulating an individual's motivation to engage in physical activity remain incompletely understood. An important factor stimulating the engagement in both competitive and recreational exercise is the motivating pleasure derived from prolonged physical activity, which is triggered by exercise induced neurochemical changes in the brain. Here, we report on the discovery of a gut brain connection in mice that enhances exercise performance by augmenting dopamine signalling during physical activity. We find that microbiome dependent production of endocannabinoid metabolites in the gut stimulates the activity of TRPV1 expressing sensory neurons and thereby elevates dopamine levels in the ventral striatum during exercise. Stimulation of this pathway improves running performance, whereas microbiome depletion, peripheral endocannabinoid receptor inhibition, ablation of spinal afferent neurons or dopamine blockade abrogate exercise capacity. These findings indicate that the rewarding properties of exercise are influenced by gut derived interoceptive circuits and provide a microbiome dependent explanation for interindividual variability in exercise performance. Our study also suggests that interoceptomimetic molecules that stimulate the transmission of gut derived signals to the brain may enhance the motivation for exercise. [doi:10.25345/C5H12VH9P] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Metabolomics, Microbiome, gut, brain

Contact

Principal Investigators:
(in alphabetical order) 		ANDREW DAVID Patterson, Penn State, United States
Submitting User: haihaba

Publications

Dohnalová L, Lundgren P, Carty JRE, Goldstein N, Wenski SL, Nanudorn P, Thiengmag S, Huang KP, Litichevskiy L, Descamps HC, Chellappa K, Glassman A, Kessler S, Kim J, Cox TO, Dmitrieva-Posocco O, Wong AC, Allman EL, Ghosh S, Sharma N, Sengupta K, Cornes B, Dean N, Churchill GA, Khurana TS, Sellmyer MA, FitzGerald GA, Patterson AD, Baur JA, Alhadeff AL, Helfrich EJN, Levy M, Betley JN, Thaiss CA.
A microbiome-dependent gut-brain pathway regulates motivation for exercise.
Nature. 2022 Dec;612(7941):739-747. Epub 2022 Dec 14.

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