Microbial metabolites: Bridging the gut-brain divide in ischemic stroke

The Microbiota-Gut-Brain Axis (MGBA) has recently crystallized into a focal frontier spanning neuroscience and microbiology, illuminating the intricate reciprocity between intestinal microbes and the central nervous system. Stroke, a devastating and life-threatening cerebrovascular disorder, is now recognized to have its onset, progression, and long-term outcome intimately entwined with MGBA dynamics. Accumulating empirical literature substantiates the existence of intimate bidirectional gut-brain signaling circuits, wherein the gut microbiome functions as a central modulator. This microbial consortium not only orchestrates neuroinflammatory cascades following cerebral insult, but also bio-transforms dietary and host-derived substrates into multifunctional metabolites that exert both local and systemic bioactivity. Emerging evidence suggests that individual microbial metabolites and their secondary derivatives may serve as candidate signaling intermediaries, mediating the transduction of microbial cues into neurovascular responses. Accordingly, the present review provides a forward synthesis of how the MGBA intersects with ischemic stroke pathobiology, focusing on elucidating the therapeutic potential and strategies of gut microbial metabolites in ischemic stroke. It provides theoretical insights and translational prospects for gut-derived metabolites as therapeutic targets.