Effects of acupuncture on mild cognitive impairment via the microbiota-gut-brain axis: a systematic review

Mild Cognitive Impairment (MCI) is a critical window for intervention in neurodegenerative diseases. As emerging evidence suggests the role of microbiota-gut-brain (MGB) axis on cognitive health, this systematic review aims to evaluate the efficacy and underlying mechanisms of acupuncture in modulating the MGB axis to alleviate cognitive decline.

A systematic search was conducted across PubMed/MEDLINE, Web of Science, Scopus, and Cochrane CENTRAL from inception to April 2026. Following PRISMA 2020 guidelines, we included both clinical randomized controlled trials (RCTs) and preclinical animal studies investigating acupuncture's effects on MCI via gut microbiota.

Five studies (2 clinical randomized controlled trials, n = 102 participants; 3 animal studies, n = 165 animals) met the inclusion criteria. In clinical studies, manual acupuncture significantly improved cognitive outcomes, including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). In one randomized trial, acupuncture produced a mean reduction of 3.94 points in ADAS-Cog from baseline compared with a 1.72-point increase in the waitlist group, yielding a between-group mean difference of -5.66 points (95% CI: -6.98 to -4.35) after 12 weeks. In another trial, the total clinical effective rate was significantly higher in the acupuncture group than in the control group (82.8% vs. 61.3%, p < 0.05). These cognitive improvements were accompanied by favorable alterations in gut microbiota composition, including increased abundance of butyrate-producing taxa such as Faecalibacterium, Ruminococcaceae, and Ruminococcus, and were associated with enhanced functional connectivity within the brain's default mode network on functional MRI. In animal models, electroacupuncture significantly improved spatial learning, memory performance, and exploratory behavior while reducing hippocampal neuronal damage. Mechanistically, these effects were associated with enrichment of beneficial microbial taxa, reduction of pro-inflammatory bacteria such as Proteobacteria and Escherichia-Shigella, upregulation of intestinal tight junction proteins (ZO-1 and Occludin), restoration of intestinal barrier integrity, increased serotonin (5-HT) levels, and suppression of neuroinflammatory and oxidative stress markers, including TNF-α, IL-1β, IL-6, and reactive oxygen species.

Acupuncture alleviates MCI by modulating the MGB axis, enriching beneficial microbiota to restore intestinal integrity and suppress neuroinflammation. These microbial shifts correlate with improved functional connectivity, establishing acupuncture as a potent gut-centric neuroprotective strategy for cognitive health.