Stroke remains the leading cause of serious, long-term adult disability, with hundreds of thousandsrendered 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 apriority. Age, known co-morbidities such as diabetes, and the size and location of the infarct strongly influencestroke outcome. Even after accounting for these recognized factors, much of the variability in recovery afterstroke remains unexplained. Inflammation contributes to pathophysiology of both acute ischemic injury andmore delayed injury that affects the outcomes in cerebral ischemia. One major effort in characterizing immunemechanisms in disease and immune response to injury focuses on the human microbiome. Recent data inmouse models of stroke have established a relationship between gut microbiota, neuroinflammatory responseto ischemic infarct, and outcomes. These animal studies, if recapitulated in human disease, could open anentirely novel and dramatic avenue of treatment in ischemic stroke. To date, the limited microbiome studies inhuman cerebrovascular disease have not focused on stroke outcome. We hypothesize that recovery afterischemic stroke is influenced by gut microbial composition.A secondary hypothesis is that gut microbialcomposition influences neurocognitive function after stroke.To test these hypotheses we propose usingmicrobial surveys of gastrointestinal microbiota from individuals presenting with ischemic stroke. Aim 1 willinvestigate the relationship of baseline intestinal microbial community composition with ischemicstroke outcomes at 3 months, comparing the composition and diversity of gut microbiota in those with a)excellent (NIHSS<1) versus non-excellent outcomes andb) devastating (NIHSS>20) versus non-devastatingoutcomes.Aim 2 will investigate the relationship of baseline intestinal microbial communitycomposition in those with specific neurocognitive deficits after ischemic stroke,to determine whethermicrobiota composition and diversity influence neurocognitive function after stroke.Upon successfulcompletion of this project, in addition to testing our hypotheses, we will have collected the necessaryclinical/phenotypic data and biological samples to extend our investigations to subsequent metagenomic andmechanistic studies, as well as examine the interplay between host factors and the gut microbiome on strokeoutcomeand cognitive function, thus paving the way for future novel strategies to reduce stroke morbidity.
GASTROINTESTINAL MICROBIOME AND STROKE OUTCOMES NETWORK (GEMSTONE)
Worrall, Bradford B; Sale, Michele M
University of Virginia