Gut Microbiota and Ischemic Stroke: From Pre-Stroke Dysbiosis and Acute-Phase Changes to Therapeutic Applications

Ischemic stroke poses a major global health burden, and growing evidence points to the microbiota-gut-brain axis as an important contributor to stroke pathophysiology and recovery. The purpose of this review is to summarize current knowledge on bidirectional gut-brain communication in stroke, establishing gut dysbiosis as an upstream risk factor for stroke onset and examining microbiota dynamics across acute and chronic phases.

A comprehensive review of the current literature was conducted to synthesize existing evidence on the mechanisms of gut-brain communication, the influence of host factors, post-stroke complications, and candidate therapeutic interventions targeting the MGBA in ischemic stroke.

Gut dysbiosis acts as a risk factor for stroke through TMAO-mediated atherothrombosis, systemic inflammatory priming, and comorbidity-associated dysbiotic pre-conditioning. Following a stroke, dysbiosis is characterized by a depletion of short-chain fatty acid (SCFA)-producing taxa and an expansion of pro-inflammatory bacteria, particularly Proteobacteria and Enterobacteriaceae. Host factors (age, sex, genetics, and comorbidities) shape microbiota signatures and influence outcomes. Furthermore, post-stroke complications-including cognitive impairment, depression, stroke-associated pneumonia, and gastrointestinal dysfunction-are intimately linked to persistent dysbiosis. Mechanistically, the gut microbiota modulates stroke outcomes through immune regulation, metabolite signaling, blood-brain barrier integrity, and vagal pathways. Candidate therapeutic interventions (probiotics/prebiotics, fecal microbiota transplantation, SCFA supplementation, traditional Chinese medicine, and neuromodulation) demonstrate promising neuroprotective and recovery-enhancing effects, predominantly in preclinical models.

While targeted interventions like probiotics and dietary fiber supplementation have shown modest benefits in small clinical trials, human clinical evidence remains largely preliminary. The translation of FMT, SCFA supplementation, and neuromodulatory approaches to clinical practice requires validation through rigorous, adequately powered randomized controlled trials. Future precision microbiome medicine demands individualized profiling and phenotype-specific interventions to establish microbiota-targeted strategies as viable adjunctive stroke therapies.