Gut microbiota-derived acetate promotes long-term recovery through angiogenesis guided by lymphatic ingrowth in older adults with stroke

作者：Yujia Yuan, Linlin Li, Jingjing Wang, Bat-Otgon Myagmar, Yuxiao Gao, Huan Wang, Zhao Wang, Cong Zhang, Xiangjian Zhang · 发表于：Frontiers in Neuroscience · 年份：2024 · DOI：10.3389/fnins.2024.1398913 · 被引用次数：13 · 研究领域：Gut microbiota and health、Cerebrospinal fluid and hydrocephalus、Neuroinflammation and Neurodegeneration Mechanisms

Introduction: Ischemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults. Objective: To determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis. Methods: Part I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16-18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2-3 months) or aged donors (16-18 months). Results: In older stroke patients, gut microbiota diversity was significantly reduc...