Source-aware microbial–host signaling after ischemic stroke: evidence, competing origins, and causal roles
4 affiliations
- 1Tianjin University of Traditional Chinese Medicine
- 2Shanxi University of Traditional Chinese Medicine, Jinzhong
- 3Shandong University of Traditional Chinese Medicine, Jinan
- 4Encephalopathy Acupuncture Center 2, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
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.
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BibTeX
@article{zhao2026sourceaware,
title = {{Source-aware microbial–host signaling after ischemic stroke: evidence, competing origins, and causal roles}},
author = {Xinwei Zhao and Wanyi Zhang and Zeyu Yang and Zhengyuan Liu and Linlin Zhang and Zelin Chen},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1986786},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1986786/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Source-aware microbial–host signaling after ischemic stroke: evidence, competing origins, and causal roles
AU - Xinwei Zhao
AU - Wanyi Zhang
AU - Zeyu Yang
AU - Zhengyuan Liu
AU - Linlin Zhang
AU - Zelin Chen
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1986786
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1986786/full
AB - 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.
SN - 1664-3224
ER -