Standardized Acupuncture Combined with Modified Xiaoxuming Decoction Modulates Brain–Gut Axis-Related Mechanisms in Acute Ischemic Stroke: A Randomized Controlled Trial

Acute ischemic stroke is frequently accompanied by systemic inflammation, gut microbiota dysbiosis, impaired intestinal barrier function, and altered microbial metabolites. These changes may contribute to early neurological recovery through the brain–gut axis. Standardized acupuncture and Xiaoxuming Decoction have both been used as adjunctive approaches in stroke care, but their combined effect on brain–gut axis-related mechanisms remains insufficiently defined. This randomized controlled trial evaluated whether standardized acupuncture combined with modified Xiaoxuming Decoction improved early neurological recovery and modulated brain–gut axis-related biomarkers in patients with acute ischemic stroke. In this single-center, assessor-blinded, parallel-group randomized controlled trial, 128 patients with imaging-confirmed acute ischemic stroke were randomly assigned to receive either standard acute stroke care alone or standard care plus standardized acupuncture and modified Xiaoxuming Decoction. The intervention lasted 28 days, and clinical follow-up was completed at day 90. The primary outcome was the change in National Institutes of Health Stroke Scale (NIHSS) score from baseline to day 28. Secondary outcomes included Barthel Index, modified Rankin Scale, recurrent stroke, and safety events. Exploratory mechanistic outcomes included inflammatory markers, gut barrier-related markers, fecal microbiota diversity, selected bacterial genera, short-chain fatty acids, and mediation analysis. The intervention group showed greater NIHSS improvement from baseline to day 28 than the control group, with an adjusted between-group difference of −1.18 points (95% CI, −2.05 to −0.31; P = 0.008). Barthel Index was also higher in the intervention group at day 28, while day 90 functional outcomes showed favorable but non-significant trends. The intervention group showed lower IL-6 and LPS levels, higher Shannon diversity, increased fecal butyrate, and greater abundance of selected short-chain fatty acid-producing genera at day 28. Exploratory mediation analysis suggested that fecal butyrate and IL-6 changes partly accounted for the treatment-related NIHSS improvement. No intervention-related serious adverse events were observed. Standardized acupuncture combined with modified Xiaoxuming Decoction improved early neurological recovery in patients with acute ischemic stroke and was associated with favorable changes in selected brain–gut axis-related biomarkers. These findings support a potential microbiota–metabolite–inflammation pathway, although the mechanistic results remain exploratory and require confirmation in larger multicenter trials.