| Summary: | The role of neurotrophic factors, oxidative stress, and inflammation in the pathogenesis of Alzheimer’s disease (AD) has been explored. Animal studies have reported the positive effects of probiotics on these factors. Some clinical studies also support the potential role of probiotics in improving cognitive function via the gut–brain axis in older adults. However, clinical experimental studies evaluating the efficacy of probiotics targeting the neurotrophic factors and inflammatory biomarkers, particularly among AD patients, remain very limited. In this randomized, double-blinded, active-controlled trial, we used multi-strain probiotic supplements, including <i>Bifidobacterium longum</i> subsp. <i>infantis</i> BLI-02, <i>B. breve</i> Bv-889, <i>B. animalis</i> subsp. <i>lactis</i> CP-9, <i>B. bifidum</i> VDD088, and <i>Lactobacillus plantarum</i> PL-02 as the intervention. Participants were divided into an active control group (received probiotic supplements containing 5 × 10<sup>7</sup> colony-forming units per day, CFU/day) and a treatment group (1 × 10<sup>10</sup> CFU/day). Student’s <i>t</i> test was applied as the main method of statistical analysis. After 12 weeks of intervention, the treatment group demonstrated a 36% increase in serum brain-derived neurotrophic factor (BDNF) (* <i>p</i> = 0.005), a reduction in IL-1β (* <i>p</i> = 0.041), and an increase in antioxidant superoxide dismutase (SOD) (* <i>p</i> = 0.012). No significant change was found in the active control group. A trend toward less cognitive deterioration was observed, but not statistically significant. In conclusion, this study presents evidence supporting the benefits of multi-strain probiotics in enhancing BDNF, ameliorating inflammation and oxidative stress in AD patients.
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