Research Progress on the Regulation of Microglial Polarization by Gut Microbiota in Inflammatory Ischemic Stroke

After ischemic stroke, the gut microbiota and its metabolic profile can be rapidly reshaped and influence central innate immune responses through multiple gut-immune-brain pathways. Among these processes, microglial polarization is a key step linking peripheral inflammatory cues to secondary brain injury. Available clinical and experimental evidence indicates that stroke-associated dysbiosis is commonly characterized by a decrease in SCFAs (short-chain fatty acids)-producing bacteria, such as Faecalibacterium, Roseburia, and Lachnospiraceae, together with an increase in opportunistic or inflammation-associated taxa, including Enterobacteriaceae and Porphyromonadaceae. These alterations are associated with stroke severity, poor functional outcome, and infectious complications. Mechanistically, gut microbiota dysbiosis can synergistically promote neuroinflammatory responses through multiple pathways, including microbial metabolites and endotoxin signaling (e.g., the SCFAs-GPR41/43-HDAC axis, the TMAO-related inflammatory signaling, and the LPS-TLR4 pathway), peripheral immune remodeling (e.g., Th17/Treg imbalance, monocyte/neutrophil recruitment, and cytokine release), and systemic inflammation triggered by intestinal barrier disruption. Under the combined influence of these factors, microglia shift from a relatively reparative state toward a pro- inflammatory phenotype, further activating the NF-κB signaling pathway and promoting the assembly and activation of the NLRP3 inflammasome, thereby exacerbating blood-brain barrier disruption and neuroinflammatory responses. In terms of intervention, peri-stroke nutritional support combined with probiotics or synbiotics has shown potential in some clinical studies to improve intestinal barrier function, alleviate inflammatory responses, and optimize nutritional parameters, thereby potentially reducing the risk of infection. In experimental studies, fecal microbiota transplantation, postbiotics or SCFAs supplementation, and targeted modulation of metabolic pathways such as the TMAO axis have also shown promise in alleviating brain injury and regulating microglial polarization. Overall, gut microbiota dysbiosis is an important upstream contributor to post-stroke neuroinflammation; however, the causal relationship among signature taxa, key metabolites, microglial phenotypes, and clinical outcomes still requires further confirmation by high-quality clinical studies before microbiota-targeted strategies can be translated into ischemic stroke management.

CSTR: 32200.14.cjcb.2026.04.0025