Gut microbial dysbiosis correlates with stroke severity markers in aged rats.
Gut microbial dysbiosis correlates with stroke severity markers in aged rats.
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DOI：
10.3389/fstro.2022.1026066
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发表时间：
2022-01-01
期刊：
影响因子：
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通讯作者：
Pennypacker, Keith R
中科院分区：
文献类型：
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作者：
Hammond, Tyler C;Messmer, Sarah;Pennypacker, Keith R
背景：中风后肠道微生物群落失衡，或生态失调。这种生态失调可能会对中风恢复和康复产生负面影响。中风后肠道微生物组的物种水平分辨率测量需要开发和测试精确的干预措施，如针对肠道微生物组的益生菌或粪便微生物群移植疗法。先前的研究已经在年轻雄性小鼠中使用16 S rRNA扩增子测序来获得中风后属水平上的肠道微生物组的广泛概况，但需要在两种性别的老年大鼠中使用全基因组鸟枪测序进行进一步研究，以获得模型中的物种水平分辨率，这将更好地转化为人类中风患者的人口统计学。方法：对39只老年雄性和雌性大鼠进行了大脑中动脉闭塞。在中风前和中风后3天收集粪便样品以测量肠道微生物组。机器学习用于识别在中风后发生变化的排名最高的细菌。MRI检查脑梗死、水肿范围及脑血流量。结果：病原菌如病毒丁酸单胞菌（15.52倍变化，p < 0.0001）、普通拟杆菌（7.36倍变化，p <0.0001）和大肠杆菌（47.67倍变化，p < 0.0001）的增加证明了生态失调。这些细菌与梗死和水肿大小以及炎症标志物Ccl 19、Ccl 24、IL 17 a、IL 3和补体C5正相关;它们与CBF负相关。相反，有益细菌如产黄瘤胃球菌（0.14倍变化，p < 0.0001）、嗜粘蛋白阿克曼氏菌（0.78倍变化，p < 0.0001）和鼠乳杆菌（0.40倍变化，p < 0.0001）在中风后减少，并且与致病物种相反方向的所有先前参数相关。有没有显着的微生物组之间的差异sexual.Conclusion：这里发现的物种水平的分辨率测量可以作为一个基础，开发和测试精确的干预措施，针对肠道微生物组中风后。应开发包括产黄瘤胃球菌、嗜粘蛋白阿克曼氏菌和鼠乳杆菌在内的益生菌，以靶向中风后的缺陷，从而测量对中风严重程度的影响。
Background: An imbalanced gut microbial community, or dysbiosis, has been shown to occur following stroke. It is possible that this dysbiosis negatively impacts stroke recovery and rehabilitation. Species level resolution measurements of the gut microbiome following stroke are needed to develop and test precision interventions such as probiotic or fecal microbiota transplant therapies that target the gut microbiome. Previous studies have used 16S rRNA amplicon sequencing in young male mice to obtain broad profiling of the gut microbiome at the genus level following stroke, but further investigations will be needed with whole genome shotgun sequencing in aged rats of both sexes to obtain species level resolution in a model which will better translate to the demographics of human stroke patients.Methods: Thirty-nine aged male and female rats underwent middle cerebral artery occlusion. Fecal samples were collected before stroke and 3 days post stroke to measure gut microbiome. Machine learning was used to identify the top ranked bacteria which were changed following stroke. MRI imaging was used to obtain infarct and edema size and cerebral blood flow (CBF). ELISA was used to obtain inflammatory markers.Results: Dysbiosis was demonstrated by an increase in pathogenic bacteria such as Butyricimonas virosa (15.52 fold change, p < 0.0001), Bacteroides vulgatus (7.36 fold change, p < 0.0001), and Escherichia coli (47.67 fold change, p < 0.0001). These bacteria were positively associated with infarct and edema size and with the inflammatory markers Ccl19, Ccl24, IL17a, IL3, and complement C5; they were negatively correlated with CBF. Conversely, beneficial bacteria such as Ruminococcus flavefaciens (0.14 fold change, p < 0.0001), Akkermansia muciniphila (0.78 fold change, p < 0.0001), and Lactobacillus murinus (0.40 fold change, p < 0.0001) were decreased following stroke and associated with all the previous parameters in the opposite direction of the pathogenic species. There were not significant microbiome differences between the sexes.Conclusion: The species level resolution measurements found here can be used as a foundation to develop and test precision interventions targeting the gut microbiome following stroke. Probiotics that include Ruminococcus flavefaciens, Akkermansia muciniphila, and Lactobacillus murinus should be developed to target the deficit following stroke to measure the impact on stroke severity.