Abstract：
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.
摘要：
缺血性脑卒中与肠道菌群失调和肠道屏障功能紊乱密切相关。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系统疾病的实用策略。葛根抗性淀粉（PLR-RS）是一种潜在的新型益生元；然而，其在缺血性卒中中的作用尚不清楚.本研究旨在阐明PLR-RS在缺血性卒中中的作用及其机制。采用大脑中动脉闭塞手术建立大鼠缺血性脑卒中模型。灌胃14天后，PLR-RS减轻缺血性卒中诱导的脑损害和肠屏障功能障碍。此外，PLR-RS拯救了肠道菌群失调，并丰富了Akkermansia和双歧杆菌。我们将PLR-RS处理的大鼠的粪便菌群移植到缺血性中风的大鼠中，发现脑和结肠损伤也得到了改善。值得注意的是,我们发现PLR-RS促进肠道菌群产生更高水平的褪黑激素.有趣的是，外源性灌胃褪黑素可减轻缺血性卒中损伤。特别是,褪黑激素通过肠道微生态中的阳性共生模式减轻了脑损伤。特定的有益细菌是促进肠道稳态的领导者或基石物种，如肠杆菌，拟杆菌_S24-7_组，Prevotella_9，Ruminococaceae和Lachnospirosaceae。因此，这种新的潜在机制可以解释PLR-RS治疗缺血性卒中的疗效至少部分归因于肠道微生物来源的褪黑激素.总之,通过益生元干预和肠道补充褪黑素改善肠道微生态被发现是缺血性卒中的有效治疗方法.
