Gastrointestinal Microbiome and Stroke Outcomes Network (GEMSTONE)

胃肠道微生物组和中风结果网络 (GEMSTONE)

• 批准号: 9792290
• 负责人: BRADFORD B WORRALL
• 金额: $ 20.4万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9792290
• 关键词: 16S ribosomal RNA sequencing; Accounting; Acute; Adult; Affect; Age; Animals; Biological; Biological Markers; Blood Vessels; Caring; Cerebral Ischemia; Cerebrovascular Disorders; Cessation of life; Clinical; Clinical Research; Cognitive; Comorbidity; Coupled; DNA; Data; Development; Diabetes Mellitus; Disabled Persons; Disease; Epigenetic Process; Extramural Activities; Foundations; Functional disorder; Funding; Future; Gene Expression; Genetic; Genomics; Health; Health Care Costs; Health system; Hour; Human; Human Microbiome; Hypertension; Immune; Immune response; Immune system; Impaired cognition; Individual; Infarction; Inflammation; Injury; Integration Host Factors; International; Intestines; Investigation; Investments; Ischemic Stroke; Location; Long-Term Care; Measures; Metagenomics; Microbe; Modernization; Morbidity - disease rate; Mus; Neurocognitive; Neurocognitive Deficit; Outcome; Patients; Pilot Projects; Plasma; Process; Productivity; Proteomics; RNA; Recovery; Research; Research Personnel; Research Project Grants; Resistance; Resources; Risk Factors; Sales; Sampling; Scientist; Severities; Stroke; Surveys; Survivors; Susceptibility Gene; Talents; Testing; Therapeutic Intervention; Translating; Treatment outcome; Universities; Virginia; Work; aged; animal data; clinical phenotype; cognitive function; commercialization; cost; disability; epigenomics; fecal microbiome; follow-up; gastrointestinal; gut microbiome; gut microbiota; human disease; improved outcome; innovation; metabolomics; microbial; microbial community; microbiome; microbiome research; microbiota; mortality; mouse model; neuroinflammation; neurovascular; novel; novel strategies; novel therapeutics; outcome prediction; phenotypic data; post stroke; precision medicine; response; response to injury; sample collection; stroke model; stroke outcome; stroke patient; stroke recovery; stroke risk; stroke survivor; success; targeted treatment; transcriptomics; translational research program; translational scientist; treatment response

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.

中风仍然是导致成人长期严重残疾的主要原因，有数十万人