Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou 215123, China.
Institute of Nutrition & Health, School of Public Health, Qingdao University, 38 Dengzhou Road, 266021 Qingdao, China.
Oxid Med Cell Longev. 2023 Jan 20;2023:2766250. doi: 10.1155/2023/2766250. eCollection 2023.
Gut microbes may be the critical mediators for the cognitive enhancing effects of exercise. Via fecal microbiota transplantation (FMT), this study is aimed at determining the mechanism of how voluntary exercise improved learning and memory ability impairment post a high-fat, high-cholesterol (HFHC) diet. The learning and memory abilities assessed via the Morris water maze in the FMT recipient group of voluntary exercising mice were improved compared to sedentary group. 16S rRNA gene sequencing results indicated that exercise-induced changes in gut microbiota distribution were transmissible, mainly in terms of elevated , , and , as well as decreased and after FMT. The neuroprotective effects of FMT were mainly related to the improved insulin signaling pathway (IRS2/PI3K/AKT) and mitochondrial function; inhibition of AQP4; decreased p-Tau at serine 396 and 404; increased BDNF, PSD95, and synaptophysin in the hippocampus; and also decreased HDAC2 and HDAC3 protein expressions in the nuclear and cytoplasmic fractions of the hippocampus. The findings of qRT-PCR suggested that exercise-induced gut microbes, on the one hand, elevated GPR109A and decreased GPR43 and TNF- in the hippocampus. On the other hand, it increased GPR109A and GPR41 expressions in the proximal colon tissue. In addition, total short-chain fatty acid (SCFA), acetic acid, propionic acid, isobutyric acid, valeric acid, and isovaleric acid contents were also elevated in the cecum. In conclusion, exercise-induced alterations in gut microbiota play a decisive role in ameliorating HFHC diet-induced cognitive deficits. FMT treatment may be a new considerable direction in ameliorating cognitive impairment induced by exposure to HFHC diet.
肠道微生物可能是运动增强认知的关键介质。通过粪便微生物群移植（FMT），本研究旨在确定运动如何改善高脂肪、高胆固醇（HFHC）饮食后学习和记忆能力受损的机制。与久坐组相比，通过 Morris 水迷宫评估的 FMT 接受组自愿运动小鼠的学习和记忆能力得到改善。16S rRNA 基因测序结果表明，运动引起的肠道微生物分布变化是可传递的，主要表现在 、 、 和 水平升高， 、 水平降低。FMT 的神经保护作用主要与改善的胰岛素信号通路（IRS2/PI3K/AKT）和线粒体功能有关；抑制 AQP4；减少磷酸化 Tau 丝氨酸 396 和 404 位点；增加海马脑源性神经营养因子（BDNF）、突触后密度蛋白 95（PSD95）和突触小体蛋白（synaptophysin）；以及降低海马核和细胞质部分的组蛋白去乙酰化酶 2（HDAC2）和组蛋白去乙酰化酶 3（HDAC3）蛋白表达。qRT-PCR 的结果表明，一方面，运动诱导的肠道微生物在海马中升高 GPR109A，降低 GPR43 和 TNF-α；另一方面，它增加了近端结肠组织中 GPR109A 和 GPR41 的表达。此外，盲肠中总短链脂肪酸（SCFA）、乙酸、丙酸、异丁酸、戊酸和异戊酸含量也升高。总之，运动引起的肠道微生物变化在改善 HFHC 饮食引起的认知缺陷中起决定性作用。FMT 治疗可能是改善 HFHC 饮食诱导的认知障碍的一个新的重要方向。
