Prospective Cohort Control Study on Changes in Gut Microbiota in Ischemic Stroke

1. Stroke stands as one of the leading causes of death and long-term disability worldwide, imposing a substantial socioeconomic burden. Annual new stroke cases are estimated between 9.5 million and 10.6 million. Stroke survivors commonly face challenges of poor long-term functional outcomes and compromised immunity, which not only drive quality-of-life deterioration but also fuel the persistent escalation of socioeconomic burdens. However, current clinical treatments for stroke prognosis improvement remain limited. In recent years, with the emergence of the "microbiota-gut-brain axis" concept and advancing research, the role of gut microbiota in stroke onset, progression, and prognosis regulation has garnered increasing attention. The gut-brain axis is a complex bidirectional communication network connecting the central nervous system with the gut and its microbiota, centered on the integration of the microbiota-gut-brain axis concept. Its signaling mechanisms primarily involve multiple pathways including neural (e.g., vagus nerve), endocrine (e.g., HPA axis and gut hormones), immune (e.g., cytokines), and microbial metabolic pathways (e.g., short-chain fatty acids (SCFAs) and neuroactive substances). Dysregulation of the gut-brain axis has been proven closely associated with various diseases, including irritable bowel syndrome (IBS) characterized by visceral hypersensitivity and motility abnormalities, inflammatory bowel disease (IBD) often accompanied by emotional comorbidities, autism spectrum disorder (ASD) with gastrointestinal symptoms and behavioral core symptoms, depression and anxiety related to microbiota dysbiosis and inflammation, as well as Parkinson's disease (PD) with pathological origins potentially originating in the gut. Recent studies support that gut microbiota interact with ischemic stroke through the gut-brain axis, thereby modulating stroke pathogenesis. Gut microbiota can regulate innate and adaptive immune responses and their derived metabolites through neural pathways, influencing host brain function and behavior. Gut microbiota metabolites-short-chain fatty acids (SCFAs) such as butyrate-reduce neuroinflammation and brain injury by promoting regulatory T cell differentiation and secretion of anti-inflammatory factors IL-10 and TGF-β, suppressing pro-inflammatory Th1/Th17 responses, and enhancing expression of blood-brain barrier tight junction proteins Occludin and ZO-1. Compared to traditional stroke treatments, gut microbiota therapy breaks the time window limitation. Even days after stroke, restoring a youthful gut microbiome can reduce neuroinflammation and promote recovery in stroke patients. This effect is largely mediated by metabolites produced by bacteria, particularly short-chain fatty acids. Although existing studies have demonstrated the crucial role of gut microbiota in stroke treatment, the mechanisms underlying its effects on improving physiological and behavioral functions in stroke patients, as well as the underlying mechanisms, remain insufficiently explored. 2. Purpose of this study To investigate the mechanisms by which gut microbiota and their metabolites improve the physiological and neurological functions of stroke patients, and to provide new therapeutic approaches for improving the prognosis of stroke patients. 3. Research Design 3.1 Research Methodology This is a single-center, non-interventional, cohort-controlled clinical study that randomly enrolled 100 stroke patients and 100 healthy individuals. The participants were divided into a stroke group (case group, CS group) and a healthy control group (CON group), with 100 cases in each group. The primary objectives were to investigate the gut microbiota composition, intestinal barrier function, and inflammatory cytokine levels in stroke patients versus healthy controls, while exploring the mechanisms of beneficial gut microbiota in stroke recovery. This research may provide new therapeutic approaches to address current treatment limitations.