Multistrain probiotics modulate tau pathology and preserve visuospatial cognition in early cognitive impairment: A double-blind, randomized, placebo-controlled trial

Abstract

Background The gut-brain axis is increasingly implicated in Alzheimer's disease (AD) pathogenesis. Objective To investigate whether a multistrain probiotic supplement is associated with changes in AD-related plasma biomarkers and cognitive function in older adults with early cognitive impairment. Methods In this randomized, double-blind, placebo-controlled trial, eighty-seven participants from the Gwangju Alzheimer's Disease and Related Dementias cohort were randomized to receive a multistrain probiotic (n = 40) or placebo (n = 47) for 24 weeks. Plasma phosphorylated tau 181 (pTau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were evaluated at baseline and 24 weeks. Cognitive assessments included the Clinical Dementia Rating Sum of Boxes (CDR-SB), CERAD battery, Stroop test, and Rey-Osterrieth Complex Figure (ROCF). Analyses utilized linear mixed models and ANCOVA. Results Compared to placebo, the probiotic group exhibited a significant reduction in plasma pTau181 (p < 0.001). While GFAP and NfL remained stable with probiotics, the placebo group showed significant within-group increases (p = 0.014, p = 0.041). Clinically, the probiotic group demonstrated improved CDR-SB scores (p = 0.010), primarily driven by the memory domain. Probiotics were associated with improved performance in visuospatial construction tasks (Constructional Praxis, p = 0.036; ROCF copy, p = 0.027) and preserved constructional recall, whereas the placebo group exhibited significant decline (p = 0.025). No significant between-group differences were observed in Mini-Mental State Examination, verbal memory, or executive scores. Conclusions Multistrain probiotics modulated plasma tau and neuroinflammatory biomarkers, and selectively preserved visuospatial cognition in this study. These findings suggest the potential role of microbiota-targeted interventions as a non-pharmacological adjunct for early cognitive impairment, although further studies are required to confirm underlying mechanisms.