Gut microbiota-associated metabolites and microbial components in acute ischemic stroke - Neuroimmune inflammation, biomarkers, and therapeutic targets: A narrative review.

Acute ischemic stroke (AIS) induces gut microbiota dysbiosis and intestinal barrier disruption, potentially influencing neuroimmune inflammation via altered microbial metabolites and components. This narrative review synthesizes current evidence on the mechanisms, biomarker potential, and therapeutic implications of gut microbiota-associated molecules in AIS. We searched PubMed, Web of Science, and Scopus for peer-reviewed studies published between May 1999 and May 2026. From 283 identified records, 87 animal and clinical studies met eligibility and were included. Evidence indicates that trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS), and the tryptophan (TRP)-derived metabolite quinolinic acid predominantly promote neuroinflammation. They achieve this by disrupting blood-brain barrier integrity, activating pro-inflammatory signaling, inducing excitotoxicity, or enhancing thrombosis. Conversely, short-chain fatty acids (SCFAs), kynurenic acid, indole-3-propionic acid, and secondary bile acids exert anti-inflammatory and neuroprotective effects through immune modulation and microglial polarization. Clinical studies suggest TMAO may aid first-stroke risk stratification, while fecal SCFAs, TRP-related metabolites, and circulating bile acids show potential for assessing stroke severity or functional prognosis. However, findings vary based on specimen type, disease stage, and sampling time. Therapeutic approaches targeting these molecules-including metabolite supplementation, modulation of endogenous metabolite production, and nanodelivery systems-have shown encouraging effects, primarily in preclinical models. In conclusion, gut microbiota-associated metabolites and microbial components represent promising AIS biomarkers and therapeutic targets. However, substantial methodological heterogeneity and limited clinical validation currently restrict their translation into routine practice for ischemic stroke management.