Certain probiotics have beneficial effects on the function of the central nervous system through modulation of the gut-brain axis. Here, we describe a dynamic landscape of the peptidome across multiple brain regions, modulated by oral administration of different probiotic species over various times. The spatiotemporal and strain-specific changes of the brain peptidome correlated with the composition of the gut microbiome. The hippocampus exhibited the most sensitive response to probiotic treatment. The administration of heat-killed probiotics altered the hippocampus peptidome but did not substantially change the gut microbiome. We developed a literature-mining algorithm to link the neuropeptides altered by probiotics with potential functional roles. We validated the probiotic-regulated role of corticotropin-releasing hormone by monitoring the hypothalamic-pituitary-adrenal axis, the prenatal stress–induced hyperactivity of which was attenuated by probiotics treatment. Our findings provide evidence for modulation of the brain peptidome by probiotics and provide a resource for further studies of the gut-brain axis and probiotic therapies.

某些益生菌通过调节肠脑轴对中枢神经系统的功能产生有益影响。在这里，我们描述了跨多个大脑区域的肽组的动态景观，通过不同时间口服不同益生菌物种进行调节。脑肽组的时空和菌株特异性变化与肠道微生物组的组成相关。海马体对益生菌治疗表现出最敏感的反应。热灭活益生菌的给药改变了海马肽组，但并未显着改变肠道微生物组。我们开发了一种文献挖掘算法，将益生菌改变的神经肽与潜在的功能作用联系起来。我们通过监测下丘脑 - 垂体 - 肾上腺轴验证了促肾上腺皮质激素释放激素的益生菌调节作用，益生菌治疗可以减轻产前压力引起的多动症。我们的研究结果为益生菌对脑肽组的调节提供了证据，并为进一步研究肠-脑轴和益生菌疗法提供了资源。