Abstract：
Although the gut microbiota and kynurenine (KYN) metabolism have significant protective effects against ischaemic stroke (IS), the exact mechanism has yet to be fully elucidated. Combined serum metabolomics and 16S rRNA gene sequencing were used to reveal the differences between the gut microbiota and metabolites in rats treated with or without blueberry extract. Faecal microbiota transplantation (FMT) was employed to validate the protective role of the gut microbiota in IS. Furthermore, the interaction between Prevotella and IS was also confirmed in patients. Rats with IS experienced neurological impairments accompanied by an impaired intestinal barrier and disturbed intestinal flora, which further contributed to heightened inflammatory responses. Furthermore, Prevotella played a critical role in IS pathophysiology, and a positive correlation between Prevotella and KYN was detected. The role of KYN metabolism in IS was further demonstrated by the finding that IDO was significantly upregulated and that the use of the IDO inhibitor, attenuated KYN metabolic pathway activity and ameliorated neurological damage in rats with IS. Prevotella intervention also significantly improved stroke symptoms and decreasing KYN levels in rats with IS. FMT showed that the beneficial effects of blueberry extract on IS involve gut bacteria, especially Prevotella, which were confirmed by microbiological analyses conducted on IS patients. Moreover, blueberry extract led to significant changes in kynurenic acid levels and tryptophan and IDO levels through interactions with Prevotella. Our study demonstrates for the first time that blueberry extract could modulate \"intestinal microecology-KYN metabolism\" to improve IS.
摘要：
尽管肠道菌群和犬尿氨酸（KYN）代谢对缺血性卒中（IS）有显著的保护作用，确切的机制尚未完全阐明。联合血清代谢组学和16SrRNA基因测序用于揭示用或不用蓝莓提取物处理的大鼠的肠道微生物群和代谢物之间的差异。采用粪便微生物群移植（FMT）来验证肠道微生物群在IS中的保护作用。此外，患者中也证实了Prevotella和IS之间的相互作用.患有IS的大鼠经历了神经损伤，伴有肠屏障受损和肠道菌群紊乱，这进一步加剧了炎症反应。此外，普雷沃氏菌在IS病理生理学中起着关键作用，检测到普雷沃氏菌和KYN之间呈正相关。通过发现IDO显著上调和使用IDO抑制剂进一步证明了KYN代谢在IS中的作用,减轻IS大鼠的KYN代谢途径活性并改善神经损伤。普雷沃氏菌干预还显着改善了IS大鼠的中风症状并降低了KYN水平。FMT表明，蓝莓提取物对IS的有益作用涉及肠道细菌，尤其是普雷沃氏菌,通过对IS患者进行的微生物学分析证实了这一点。此外，蓝莓提取物通过与Prevotella的相互作用导致犬尿氨酸水平以及色氨酸和IDO水平的显着变化。我们的研究首次证明蓝莓提取物可以调节“肠道微生态-KYN代谢”以改善IS。
