Abstract A023: Endovascular Therapy Rapidly Restores Gut Microbiota Homeostasis and Suppresses Systemic Inflammation in Acute Ischemic Stroke

Background: Disruption of gut microbiota is increasingly recognized as a driver of poor outcomes after acute ischemic stroke (AIS). However, whether revascularization therapy, particularly endovascular thrombectomy (EVT), can restore gut microbiota and modulate the systemic inflammatory response in the acute phase remains to be determined. Methods: 32 patients with AIS due to anterior circulation large vessel occlusion were grouped by whether they received EVT (reperfusion group)(n=17) or standard care without reperfusion (no-reperfusion group)(n=15). Gut microbiota composition, serum bacterial metabolites (trimethylamine N-oxide [TMAO], short-chain fatty acids [SCFAs]), and inflammatory cytokines were assessed at baseline and up to 7 days post-stroke. Neurological outcomes were measured by NIHSS and mRS. Brain infarct volume was determined by MRI. Results: By day 3 after admission, EVT-treated patients exhibited significantly greater gut microbial diversity (ACE index: 132.6 ± 21.1 vs. 103.9 ± 18.6, p=0.05) and higher abundance of Bacteroidota abundance (27.6% vs. 15.3%, p=0.023), as compared to the no-reperfusion group, which had increased Proteobacteria (14.7% vs. 7.8%, p=0.046). TMAO levels remained stable after EVT but rose in the no-reperfusion group (from 1.02×10 3 ± 1.26×10 to 3.23×10 4 ± 4.39×10 4 ng/mL, p<0.05). SCFA concentrations (acetate, isobutyrate, isovalerate) increased in the EVT group by day 3 (p<0.01), with no change in the no-reperfusion group. Pro-inflammatory cytokines (IL-6: 17.4 ± 6.2 vs. 27.9 ± 10.1 pg/mL, p<0.05) decreased significantly after EVT. EVT patients had smaller infarct volumes (41.8 ± 19.5 vs. 76.5 ± 18.6 mL, p<0.01), greater improvement in NIHSS scores at day 7 (2.8 vs. 5.5, p<0.05), better functional independence at 90 days (mRS 0–2: 70.6% vs. 26.7%, p<0.01), and no 90-day mortality (vs. 1 death in no-reperfusion group). Conclusion: This is the first clinical study that EVT not only restore brain perfusion but also rapidly reestablishes gut microbiota homeostasis in acute stage of stroke. EVT as a dual-action therapy with both neurovascular and systemic immune-metabolic benefits highlights a fundamental shift of its therapeutic impact. Microbiota-targeted interventions may not be required post-EVT acute phase, though the role in chronic recovery period needs further investigation. This pioneering work establishes EVT as a cornerstone intervention bridging brain and gut, opening new avenues for integrated stroke care.