Dietary plant polysaccharides as modulators of brain aging: mechanistic links to inflammaging, the gut brain axis and amyloid tau pathology.

Abstract

<b>Objectives:</b> This review critically evaluates chemically characterized plant-derived polysaccharides (PS) as dietary modulators of brain aging, focusing on their structural features, gut-brain mechanisms and effects on neuroinflammation, amyloid pathology and tau-related pathways.<b>Methods:</b> Molecular, in vitro, preclinical and early human studies were critically examined. Evidence was assessed in relation to PS molecular weight, branching, charge, monosaccharide composition, purity, fermentability, dosage and associated non-carbohydrate constituents. Particular attention was given to gut microbiota modulation, short-chain fatty acid (SCFA) production, barrier integrity, immune signaling, microglial activation and neurodegenerative biomarkers.<b>Results:</b> Fermentable plant PS altered gut microbial composition and increased acetate, propionate and butyrate production in experimental models. These SCFAs may influence brain aging through FFAR2/FFAR3 signaling and histone deacetylase inhibition, thereby improving intestinal barrier function, regulating peripheral inflammation and modifying microglial responses. Direct anti-amyloid effects were supported mainly by in vitro studies, whereas evidence for tau modulation remained indirect and predominantly preclinical. Animal studies provided the strongest causal support, particularly through microbiota-transfer, antibiotic-depletion and receptor-pathway experiments. Human evidence was limited to associative studies and small fiber or prebiotic trials. Reported PS molecular masses ranged from about 10 kDa to more than 1,000 kDa, with preclinical doses of 50-500 mg/kg and human intakes of 5-15 g/day.<b>Discussion:</b> Plant PS are promising dietary modulators of brain aging but not established neurotherapeutics. Translation requires standardized fractions, control of co-extracted phenolics and proteins, dose-response studies and biomarker-rich clinical trials incorporating stool and plasma SCFAs, inflammatory markers, neurofilament light, phosphorylated tau, cognitive outcomes and neuroimaging measures.