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Source-aware microbial–host signaling after ischemic stroke: evidence, competing origins, and causal roles

Year: 2026
Type: review
Abstract: Ischemic stroke initiates a well-established sterile inflammatory response in injured brain tissue. Experimental studies report post-stroke intestinal barrier and mucosal changes, viable bacterial dissemination to peripheral compartments in selected animal models, and microbiota-associated material in ischemic brain tissue. Human cohorts associate gut community or metabolite profiles with infection and clinical outcomes, while microbiome-based models predict stroke-associated pneumonia or functional outcomes. These observations differ in signal identity, sampling time, source tracing, and measured destination. Gut-to-periphery dissemination in one model does not establish that brain-associated signals are viable or intestinal in origin; oral, airway, aspiration-related, infectious, and other peripheral sources remain plausible. This narrative Review synthesizes human and experimental evidence across five connected links: anatomical source, molecular identity, transport route, receptor or sensing cell, and tissue consequence. We distinguish transport from recognition and source attribution from causal-role assignment. Current evidence supports context-dependent intestinal participation and established brain-derived damage-associated molecular pattern (DAMP) signaling, but not a universal gut-to-brain causal cascade. We outline longitudinal source-to-target sampling, barrier and exposure measurements, signal-specific tracing, and timed perturbation to test each link.
Language: English
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222928574
FWCI:
Cites: 113
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Related to: 10