Hammond Tyler C, Messmer Sarah, Frank Jacqueline A, Lukins Doug, Colwell Rita, Lin Ai-Ling, Pennypacker Keith R
Lin Brain Lab, Department of Neuroscience, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States.
Department of Neurology, The Center for Advanced Translational Stroke Science, University of Kentucky, Lexington, KY, United States.
Front Stroke. 2022;1. doi: 10.3389/fstro.2022.1026066. Epub 2022 Dec 21.
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.
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.
Dysbiosis was demonstrated by an increase in pathogenic bacteria such as (15.52 fold change, < 0.0001), (7.36 fold change, < 0.0001), and (47.67 fold change, < 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 (0.14 fold change, < 0.0001), (0.78 fold change, < 0.0001), and (0.40 fold change, < 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.
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 should be developed to target the deficit following stroke to measure the impact on stroke severity.
中风后肠道微生物群落失衡，即生态失调，已被证实会发生。这种生态失调可能会对中风恢复和康复产生负面影响。需要对中风后的肠道微生物群进行物种水平分辨率测量，以开发和测试针对肠道微生物群的精准干预措施，如益生菌或粪便微生物群移植疗法。先前的研究在年轻雄性小鼠中使用16S rRNA扩增子测序，以在中风后获得属水平的肠道微生物群广泛概况，但还需要对老年雌雄大鼠进行全基因组鸟枪法测序，以便在一个能更好地转化为人类中风患者人口统计学特征的模型中获得物种水平分辨率。
39只老年雌雄大鼠接受大脑中动脉闭塞手术。在中风前和中风后3天收集粪便样本以测量肠道微生物群。使用机器学习来识别中风后变化最显著的细菌。使用MRI成像来获取梗死灶和水肿大小以及脑血流量（CBF）。使用ELISA来获取炎症标志物。
生态失调表现为病原菌增加，如（变化15.52倍，<0.0001）、（变化7.36倍，<0.0001）和（变化47.67倍，<0.0001）。这些细菌与梗死灶和水肿大小以及炎症标志物Ccl19、Ccl24、IL17a、IL3和补体C5呈正相关；它们与脑血流量呈负相关。相反，有益菌如（变化0.14倍，<0.0001）、（变化0.78倍，<0.0001）和（变化0.40倍，<0.0001）在中风后减少，并且与所有先前参数的相关性与病原菌相反。两性之间的微生物群没有显著差异。
此处发现的物种水平分辨率测量结果可作为开发和测试中风后针对肠道微生物群的精准干预措施的基础。应开发包含的益生菌，以针对中风后的缺陷来测量对中风严重程度的影响。
