Immuno-Metabolic Interactions Along the Microbiota-Gut-Brain Axis in Ischemic Stroke: A Narrative Review.

Authors

Zhengyuan Liu, Xinwei Zhao, Zeyu Yang, Linlin Zhang

Published in

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. Pages 108731. Aug 19, 2026. Epub Aug 19, 2026.

Abstract

Ischemic stroke (IS) remains a leading global cause of mortality and disability. Although current reperfusion strategies have advanced, the complex pathological mechanisms underlying IS continue to significantly limit clinical prognosis. Recently, the pivotal role of the microbiota-gut-brain axis (MGBA) in the pathological evolution of IS has garnered widespread attention. This review systematically delineates the multidimensional regulatory roles of the gut microbiota and its metabolites in IS pathogenesis, with a specific focus on immuno-metabolic crosstalk, cellular senescence, and programmed cell death.
Emerging evidence indicates that IS-induced central stress is accompanied by intestinal mucosal barrier dysfunction and gut microbial dysbiosis. Increased intestinal permeability may facilitate the systemic translocation of microbial products and inflammatory mediators, thereby promoting peripheral immune activation and the recruitment of immune cells to the ischemic brain. Aging-associated microbial disturbances and chronic inflammation may further modify these responses and contribute to heterogeneous stroke outcomes. Microbiota-derived metabolites, particularly short-chain fatty acids, participate in immune and metabolic regulation through receptor-mediated and epigenetic mechanisms. However, direct evidence demonstrating the migration of gut-derived immune cells into the human ischemic brain or microbiota-mediated regulation of neuronal ferroptosis remains limited.
Current evidence supports an association between MGBA dysfunction and the immunometabolic responses involved in IS. Further longitudinal human studies and mechanistically informed clinical trials are required to determine whether microbiota-targeted strategies can improve prevention, prognostic assessment, or treatment.

PMID:
42617992
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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