Lian Zhuoshi, Xu Ying, Wang Chan, Chen Ye, Yuan Li, Liu Zhongyu, Liu Yarui, He Peishi, Cai Zheng, Zhao Jie
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Department of Gastroenterology, Integrative Clinical Microecology Center, Shenzhen Hospital, Southern Medical University, Shenzhen 518100, China.
Pharmacol Res. 2023 Apr;190:106714. doi: 10.1016/j.phrs.2023.106714. Epub 2023 Feb 28.
Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the intestinal microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) is a potential novel prebiotic; however, its role in ischemic stroke remains unknown. This study aimed to clarify the effects and underlying mechanisms of PLR-RS in ischemic stroke. Middle cerebral artery occlusion surgery was performed to establish a model of ischemic stroke in rats. After gavage for 14 days, PLR-RS attenuated ischemic stroke-induced brain impairment and gut barrier dysfunction. Moreover, PLR-RS rescued gut microbiota dysbiosis and enriched Akkermansia and Bifidobacterium. We transplanted the fecal microbiota from PLR-RS-treated rats into rats with ischemic stroke and found that the brain and colon damage were also ameliorated. Notably, we found that PLR-RS promoted the gut microbiota to produce a higher level of melatonin. Intriguingly, exogenous gavage of melatonin attenuated ischemic stroke injury. In particular, melatonin attenuated brain impairment via a positive co-occurrence pattern in the intestinal microecology. Specific beneficial bacteria served as leaders or keystone species to promoted gut homeostasis, such as Enterobacter, Bacteroidales_S24-7_group, Prevotella_9, Ruminococcaceae and Lachnospiraceae. Thus, this new underlying mechanism could explain that the therapeutic efficacy of PLR-RS on ischemic stroke at least partly attributed to gut microbiota-derived melatonin. In summary, improving intestinal microecology by prebiotic intervention and melatonin supplementation in the gut were found to be effective therapies for ischemic stroke.
缺血性中风与肠道微生物群失调和肠道屏障功能障碍密切相关。益生元干预可以调节肠道微生物群，因此被认为是治疗神经疾病的一种切实可行的策略。葛根抗性淀粉（PLR-RS）是一种潜在的新型益生元；然而，其在缺血性中风中的作用尚不清楚。本研究旨在阐明PLR-RS在缺血性中风中的作用及其潜在机制。通过大脑中动脉闭塞手术建立大鼠缺血性中风模型。灌胃14天后，PLR-RS减轻了缺血性中风诱导的脑损伤和肠道屏障功能障碍。此外，PLR-RS改善了肠道微生物群失调，增加了阿克曼氏菌属和双歧杆菌属。我们将PLR-RS处理的大鼠的粪便微生物群移植到缺血性中风大鼠中，发现脑损伤和结肠损伤也得到了改善。值得注意的是，我们发现PLR-RS促进肠道微生物群产生更高水平的褪黑素。有趣的是，外源性灌胃褪黑素减轻了缺血性中风损伤。特别是，褪黑素通过肠道微生态中的正共现模式减轻了脑损伤。特定的有益细菌作为主导或关键物种促进肠道稳态，如肠杆菌属、拟杆菌S24-7组、普雷沃氏菌属9、瘤胃球菌科和毛螺菌科。因此，这种新的潜在机制可以解释PLR-RS对缺血性中风的治疗效果至少部分归因于肠道微生物群衍生的褪黑素。总之，通过益生元干预改善肠道微生态和在肠道中补充褪黑素被发现是治疗缺血性中风的有效疗法。
