Nature—脑肠轴研究重磅突破：肠道微生物代谢物通过刺激肠道TRPV1神经元进而诱导腹侧纹状体多巴胺的释放并激发运动欲望

中文摘要

运动对健康的生理机能有着广泛的有益影响。然而，调节个人参与体育锻炼动机的机制仍不完全清楚。刺激参与竞技性和娱乐性运动的一个重要因素是来自长期体育活动的刺激性快感，这是由运动引起的大脑神经化学变化引发的。在这里，科学家报告其在小鼠体内发现的一种肠-脑连接通路，它通过增强身体活动期间的多巴胺信号来增强运动欲望。他们发现，肠道微生物组依赖性产生内源性大麻素代谢产物，这些代谢物会刺激表达TRPV1的感觉神经元的活动，从而在运动期间提高腹侧纹状体中的多巴胺水平。这一途径的刺激改善了跑步成绩，而微生物组耗竭、外周内源性大麻素受体抑制、脊髓传入神经元的删除或多巴胺阻断则削弱了运动能力。这些发现表明，运动的奖赏特性受到肠道衍生的感觉环路的影响，并为运动表现的个体间差异提供了微生物组依赖性解释。他们的研究还表明，刺激肠源信号传递到大脑的电纳间分子可能会增强运动的动机。

英文摘要

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.

参考文献：A microbiome-dependent gut-brain pathway regulates motivation for exercise. Nature. 2022 Dec 14. doi: 10.1038/s41586-022-05525-z. Online ahead of print.

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