Unveiling the hidden culprit: How the brain-gut axis fuels neuroinflammation in ischemic stroke.

Background: The brain-gut axis represents a bidirectional communication network between the gut microbiome and the central nervous system that plays an important role in homeostasis. Compelling evidence now confirms that ischemic stroke disrupts this delicate balance by inducing gut dysbiosis. Methods: A comprehensive literature search was performed in PubMed, Web of Science, and Google Scholar for articles published between January 2000 and January 2023 using relevant keywords. Studies were limited to English and included original studies, literature, and systematic reviewers from peer-reviewed journals which discussed gut microbiota composition in models/subjects with ischemic stroke or assessed stroke impact on gut microbiota. Comments, meeting abstracts, and case reports were excluded. From the 80 relevant articles, we summarized key findings related to gut microbiota changes after stroke and their association with stroke outcomes. Results: Emerging preclinical evidence underscores the pivotal role of the gut microbiome in glial cell development and function. Germ-free models exhibit compromised microglial activation and impaired cellular debris clearance, exacerbating tissue damage following ischemic stroke. Targeted interventions, including prebiotics, probiotics, and fecal microbiota transplantation, have demonstrated efficacy in rescuing glial phenotypes in preclinical stroke models. Beyond its local effects, the gut microbiome significantly influences systemic immunity. Ischemic stroke polarizes pro-inflammatory phenotypes of neutrophils and T cells, amplifying neurovascular inflammation. Microbiota manipulation modulates leukocyte trafficking and metabolic signaling, offering potential avenues to mitigate infarct pathology. Conclusion: Our review demonstrates that in preclinical stroke models, modulating the lipopolysaccharide, short-chain fatty acid, and trimethylamine N-oxide pathways through the gut-brain axis reduces infarct sizes and edema and improves functional recovery after ischemic stroke. Further exploration of this important axis may unveil additional adjunctive stroke therapies by elucidating the complex interplay between the microbiome and the brain. Rigorously controlled clinical studies are now warranted to translate these promising preclinical findings and investigate whether manipulating the microbiome-brain relationship can help improve outcomes for stroke patients. Overall, continued research on the gut-brain axis holds exciting possibilities for developing novel treatment strategies that may enhance recovery after stroke.