Efficacy of Probiotic Supplements on Brain-Derived Neurotrophic Factor, Inflammatory Biomarkers, Oxidative Stress and Cognitive Function in Patients with Alzheimer's Dementia: A 12-Week Randomized, Double-Blind Active-Controlled Study

Abstract

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 Bifidobacterium longum subsp. infantis BLI-02, B. breve Bv-889, B. animalis subsp. lactis CP-9, B. bifidum VDD088, and Lactobacillus plantarum PL-02 as the intervention. Participants were divided into an active control group (received probiotic supplements containing 5 × 10⁷ colony-forming units per day, CFU/day) and a treatment group (1 × 10¹⁰ CFU/day). Student's t 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) (* p = 0.005), a reduction in IL-1β (* p = 0.041), and an increase in antioxidant superoxide dismutase (SOD) (* p = 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.

Keywords: Alzheimer’s disease; anti-inflammation; brain-derived neurotrophic factor (BDNF); clinical trial; cognitive function; oxidative stress; probiotics.

Figure 1

Clinical flowchart of AD patient enrollment.

Figure 2

Serum BDNF levels were analyzed at baseline and after 12 weeks of probiotic intervention in active control and treatment groups of AD patients. BDNF = brain-derived neurotrophic factor; * p < 0.05, ** p < 0.01, indicating a significant difference either within or between groups.

Figure 3

Probiotic supplements modulated inflammation, cortisol, and oxidative stress in AD patients. Serum levels of (A) IL-1β, (B) IL-10, (C) cortisol, (D) MDA, (E) PCC, and (F) SOD activity were analyzed at baseline and after 12 weeks of probiotic intervention in active control- and treatment-group AD patients. The values before and after the intervention were plotted on the left Y-axis, while the fold change was plotted on the right Y-axis. IL-1β = interleukin-1 beta; IL-10 = interleukin-10; SOD = superoxide dismutase; MDA = malondialdehyde; PCC = protein carbonyl content. * p < 0.05 indicates a significant difference either within or between groups.

Figure 4

The ORs with 95% confidence intervals (95% CI) for the active control or treatment group in a 12-week intervention with probiotic supplements on AD assessment scales have been determined. These ORs with 95% CIs were used as dichotomous variables to assess whether there was a deterioration when comparing scores between before and after the intervention. ORs = odds ratios; ADAS-Cog = Alzheimer’s Disease Assessment Scale-Cognitive Subscale; MMSE = Mini-Mental State Examination; ADL = Activities of Daily Living; CDR = Clinical Dementia Rating.

Figure 5

Gut microbiota diversity, the top 7 phyla, and altered genera after a 12-week probiotic intervention in AD patients were analyzed. (A) Alpha diversity, (B) beta diversity, (C) the composition of the top 7 most abundant phyla, and (D) the changed genera in the treatment group were examined.