一条依赖于微生物的肠道大脑途径调节运动的动机

美国宾夕法尼亚大学Christoph A. Thaiss研究团队发现，一条依赖于微生物的肠道-大脑途径调节运动的动机。相关论文于2022年12月14日在线发表在《自然》杂志上。

研究人员报告了在小鼠中发现了一种肠道与大脑的联系，它通过在体育活动中增强多巴胺信号来提高运动表现。研究人员发现，肠道内依赖微生物产生的内源性大麻素代谢物刺激了表达TRPV1的感觉神经元的活动，从而提高了运动期间腹侧纹状体的多巴胺水平。对这一途径的刺激可以提高跑步成绩，而微生物组的耗竭、外周内源性大麻素受体的抑制、脊髓传入神经元的去除或多巴胺的阻断则会削弱运动能力。

这些发现表明，运动的奖赏特性受肠道派生的互感回路的影响，并为运动表现的个体间差异性提供了一个依赖于微生物群的解释。这项研究还表明，刺激肠道信号向大脑传输的仿生分子可能会增强运动的动机。

据悉，运动对健康的生理学产生了广泛的有益影响。然而，人们对调节个人参与体育活动动机的机制仍不完全了解。刺激参与竞争性和娱乐性运动的一个重要因素是长时间的体育活动所带来的激励性快乐，这种快乐是由运动引起的大脑神经化学变化所触发的。

附：英文原文

Title: A microbiome-dependent gut–brain pathway regulates motivation for exercise

Author: Dohnalov, Lenka, Lundgren, Patrick, Carty, Jamie R. E., Goldstein, Nitsan, Wenski, Sebastian L., Nanudorn, Pakjira, Thiengmag, Sirinthra, Huang, Kuei-Pin, Litichevskiy, Lev, Descamps, Hlne C., Chellappa, Karthikeyani, Glassman, Ana, Kessler, Susanne, Kim, Jihee, Cox, Timothy O., Dmitrieva-Posocco, Oxana, Wong, Andrea C., Allman, Erik L., Ghosh, Soumita, Sharma, Nitika, Sengupta, Kasturi, Cornes, Belinda, Dean, Nitai, Churchill, Gary A., Khurana, Tejvir S., Sellmyer, Mark A., FitzGerald, Garret A., Patterson, Andrew D., Baur, Joseph A., Alhadeff, Amber L., Helfrich, Eric J. N., Levy, Maayan, Betley, J. Nicholas, Thaiss, Christoph A.

Issue&Volume: 2022-12-14

Abstract: Exercise exerts a wide range of beneficial effects for healthy physiology1. 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: 10.1038/s41586-022-05525-z

Source: https://www.nature.com/articles/s41586-022-05525-z