Gastrointestinal Microbiome and Stroke Outcomes Network (GEMSTONE)

中风仍然是成人长期严重残疾的主要原因，有数十万人 在美国每年都会导致残疾。这种残疾转化为数十亿美元的医疗费用， 失去生产力和长期护理。因此，找到降低中风发病率和改善预后的方法是一种 优先考虑。年龄、已知的糖尿病等并存疾病以及梗死灶的大小和位置对预后有很大影响。 中风结局。即使在考虑了这些公认的因素后，经济复苏的大部分变异性 中风仍未得到解释。炎症在急性缺血性损伤的病理生理学中起作用 更多影响脑缺血预后的迟发性损伤。一项主要的研究工作是确定免疫 疾病和对损伤的免疫反应的机制主要集中在人类微生物组上。最近的数据在 中风小鼠模型已经建立了肠道微生物区系与神经炎性反应之间的关系 到缺血性脑梗塞，以及结果。这些动物研究，如果在人类疾病中重述，可能会打开一个 治疗缺血性中风的全新而戏剧性的途径。到目前为止，有限的微生物组研究在 人类脑血管疾病并没有关注中风的结果。我们假设经济复苏之后 缺血性中风受肠道微生物组成的影响。 第二个假设是肠道微生物 成分会影响中风后的神经认知功能。 为了检验这些假设，我们建议使用 缺血性卒中患者胃肠道微生物区系的微生物调查。目标1将 探讨基础肠道微生物群落组成与缺血的关系 3个月后的卒中预后，比较患有A)的患者肠道微生物区系的组成和多样性 优秀(NIHSS&lt；1)与不优秀的结果和 B)破坏性(NIHSS&>20)与非破坏性 结果。 目的2将调查基线肠道微生物群落之间的关系 缺血性中风后有特定神经认知缺陷的人的成分， 以确定是否 微生物群的组成和多样性影响中风后的神经认知功能。 成功后 完成这个项目后，除了检验我们的假设外，我们还将收集必要的 临床/表型数据和生物样本，将我们的研究扩展到后续的元基因组和 机制研究，以及检验宿主因素和肠道微生物群在中风中的相互作用 结果 和认知功能 从而为未来减少中风发病率的新策略铺平了道路。

Stroke remains the leading cause of serious, long-term adult disability, with hundreds of thousands rendered disabled in the U.S. each year. This disability translates into billions of dollars in health care costs, lost productivity, and long-term care. Thus, finding ways to reduce stroke morbidity and improve outcomes is a priority. Age, known co-morbidities such as diabetes, and the size and location of the infarct strongly influence stroke outcome. Even after accounting for these recognized factors, much of the variability in recovery after stroke remains unexplained. Inflammation contributes to pathophysiology of both acute ischemic injury and more delayed injury that affects the outcomes in cerebral ischemia. One major effort in characterizing immune mechanisms in disease and immune response to injury focuses on the human microbiome. Recent data in mouse models of stroke have established a relationship between gut microbiota, neuroinflammatory response to ischemic infarct, and outcomes. These animal studies, if recapitulated in human disease, could open an entirely novel and dramatic avenue of treatment in ischemic stroke. To date, the limited microbiome studies in human cerebrovascular disease have not focused on stroke outcome. We hypothesize that recovery after ischemic stroke is influenced by gut microbial composition. A secondary hypothesis is that gut microbial composition influences neurocognitive function after stroke. To test these hypotheses we propose using microbial surveys of gastrointestinal microbiota from individuals presenting with ischemic stroke. Aim 1 will investigate the relationship of baseline intestinal microbial community composition with ischemic stroke outcomes at 3 months, comparing the composition and diversity of gut microbiota in those with a) excellent (NIHSS<1) versus non-excellent outcomes and b) devastating (NIHSS>20) versus non-devastating outcomes. Aim 2 will investigate the relationship of baseline intestinal microbial community composition in those with specific neurocognitive deficits after ischemic stroke, to determine whether microbiota composition and diversity influence neurocognitive function after stroke. Upon successful completion of this project, in addition to testing our hypotheses, we will have collected the necessary clinical/phenotypic data and biological samples to extend our investigations to subsequent metagenomic and mechanistic studies, as well as examine the interplay between host factors and the gut microbiome on stroke outcome and cognitive function , thus paving the way for future novel strategies to reduce stroke morbidity.