Correlation Between Gut Microbiota Shifts, Lipopolysaccharide Levels, and Neuroinflammatory Responses Following Ischemic Stroke

Abstract

Highlights What are the main findings? Ischemic stroke is accompanied by elevated LPS levels in the gut, circulation, and brain. Changes in gut Verrucomicrobiota abundance are spatially associated with increased LPS immunoreactivity in the ischemic brain. What are the implications of the main findings? These findings reveal a correlation between gut microbial shifts, circulating LPS, and cerebral LPS immunoreactivity, providing an observational foundation for future mechanistic studies. LPS may serve as a correlative marker linking gut microbiota changes to neuroinflammation after ischemic stroke. Abstract Background: The microbiota–gut–brain axis (MGBA) is increasingly recognized as a contributor to ischemic stroke pathophysiology, yet the relationship between gut microbial changes and neuroinflammation remains incompletely understood. This study aimed to investigate whether shifts in gut microbiota are associated with concurrent changes in lipopolysaccharide (LPS) levels and neuroinflammatory responses following ischemic stroke. Methods: Using a photothrombotic mouse model, we measured LPS in the gut, serum, and brain via ELISA and immunohistochemistry. Gentamycin was administered to deplete gut bacteria and assess its effects on LPS and stroke recovery. Upon TLR4 inhibition with TAK-242, microglial polarization and inflammatory cytokines were evaluated, and dose-dependent LPS supplementation was performed. Results: Ischemic stroke was accompanied by elevated LPS levels in the gut, circulation, and brain, paralleling Verrucomicrobiota expansion. Antibiotic treatment reduced Verrucomicrobiota and LPS in the gut and brain, and this was associated with worsened stroke outcomes. TLR4 inhibition was associated with altered microglial phenotypes and inflammatory markers. Exogenous LPS produced dose-dependent effects, whereas endogenous LPS levels remained low. Conclusions: These findings reveal a spatial correlation between gut microbial shifts, circulating LPS, and cerebral LPS immunoreactivity, suggesting LPS may serve as a correlative marker of gut–brain interactions following ischemic stroke.