Abstract / Summary
Acute ischemic stroke is accompanied by systemic inflammation and intestinal microbial disturbance. This single-center, assessor-blinded randomized controlled trial tested whether standardized acupuncture plus modified Xiaoxuming Decoction, added to standard care, improved early neurological recovery and was associated with predefined gut and inflammatory biomarkers. Adults with imaging-confirmed acute ischemic stroke within 72 h and a National Institutes of Health Stroke Scale (NIHSS) score of 4-15 were randomized 1:1 to standard care or the combined intervention for 28 days, with 64 participants per group. The primary endpoint was day-28 NIHSS adjusted for baseline NIHSS, age, sex, reperfusion therapy, and onset-to-randomization time, with missing outcomes handled by 30-fold multiple imputation. Secondary and exploratory outcomes included the Barthel Index, day-90 modified Rankin Scale (mRS), adverse events, inflammatory markers, lipopolysaccharide (LPS), fecal microbial diversity, selected genera, and short-chain fatty acids. Multiple imputation analysis estimated a lower day-28 NIHSS score in the intervention group (adjusted difference: -1.30 points; 95% confidence interval: -2.36 to -0.24; P = 0.017). Day-28 Barthel Index was higher, whereas day-90 NIHSS, Barthel Index, and observed mRS 0-2 did not differ significantly. At day 28, the intervention group had higher Shannon diversity and fecal butyrate and lower interleukin-6 and LPS. Participant-level changes in butyrate, interleukin-6, LPS, and Shannon diversity were not significantly associated with NIHSS change; therefore, mediation analysis was not performed. No intervention-related serious adverse event was identified. The combined intervention was associated with modest early neurological improvement and selected biomarker differences, but the biological findings are exploratory and do not establish a causal brain-gut pathway.