Postoperative cognitive dysfunction (POCD) affects the outcome of millions of patients each year. Aging is a risk factor for POCD. Here, we showed that surgery induced learning and memory dysfunction in adult mice. Transplantation of feces from surgery mice but not from control mice led to learning and memory impairment in non-surgery mice. Low intensity exercise improved learning and memory in surgery mice. Exercise attenuated surgery-induced neuroinflammation and decrease of gut microbiota diversity. These exercise effects were present in non-exercise mice receiving feces from exercise mice. Exercise reduced valeric acid, a gut microbiota product, in the blood. Valeric acid worsened neuroinflammation, learning and memory in exercise mice with surgery. The downstream effects of exercise included attenuating growth factor decrease, maintaining astrocytes in the A2 phenotypical form possibly via decreasing C3 signaling and improving neuroplasticity. Similar to these results from adult mice, exercise attenuated learning and memory impairment in old mice with surgery. Old mice receiving feces from old exercise mice had better learning and memory than those receiving control old mouse feces. Surgery increased blood valeric acid. Valeric acid blocked exercise effects on learning and memory in old surgery mice. Exercise stabilized gut microbiota, reduced neuroinflammation, attenuated growth factor decrease and preserved neuroplasticity in old mice with surgery. These results provide direct evidence that gut microbiota alteration contributes to POCD development. Valeric acid is a mediator for this effect and a potential target for brain health. Low intensity exercise stabilizes gut microbiota in the presence of insult, such as surgery.

术后认知功能障碍 (POCD) 每年影响数百万患者的预后。衰老是 POCD 的危险因素。在这里，我们发现手术会导致成年小鼠的学习和记忆功能障碍。移植手术小鼠而非对照小鼠的粪便会导致非手术小鼠的学习和记忆障碍。低强度运动改善了手术小鼠的学习和记忆力。运动减轻了手术引起的神经炎症和肠道微生物群多样性的减少。这些运动效果存在于接受运动小鼠粪便的非运动小鼠中。运动可以减少血液中的戊酸（一种肠道微生物群产物）。戊酸在手术后使运动小鼠的神经炎症、学习和记忆恶化。运动的下游影响包括减弱生长因子的减少，可能通过减少 C3 信号传导和改善神经可塑性来维持 A2 表型形式的星形胶质细胞。与成年小鼠的这些结果相似，运动减轻了接受手术的老年小鼠的学习和记忆障碍。接受老年运动小鼠粪便的老年小鼠比接受对照老年小鼠粪便的老年小鼠具有更好的学习和记忆力。手术增加血戊酸。戊酸阻断运动对老年手术小鼠学习和记忆的影响。运动稳定了肠道微生物群，减少了神经炎症，减弱了生长因子的减少，并在手术后的老年小鼠中保持了神经可塑性。这些结果提供了直接证据，表明肠道微生物群的改变有助于 POCD 的发展。戊酸是这种效应的介质，也是大脑健康的潜在目标。