Ameliorative Effects of Butyrylated Starch on Cognitive Dysfunction in d -Galactose-Induced Aging Mice: A Comparative Analysis with Exogenous Butyrate and Resistant Starch

Butyric acid improves cognitive dysfunction. Therefore, butyrylated starch acts as a butyrate carrier and resistant starch to produce butyric acid, potentially improving cognitive dysfunction. In the d -galactose-induced aging mice model, BNMS2 effectively improved cognitive dysfunction and outperformed sodium butyrate and high-amylose maize starch. BNMS2 ameliorated cognitive behavior and brain histopathology, decreased GFAP, IBA-1, Aβ, AChE, MDA, IL-6, IL-1β, and TNF-α levels, and increased BDNF, PSD-5, GSH-Px, and SOD levels to mitigate neuronal damage, oxidative stress, and inflammation. BNMS2 also produced abundant butyric acid, enhanced the abundance of beneficial bacteria ( Alistipes, Parasutterella, Parabacteroides, Lachnospiraceae_UCG-006, Muribaculum ) and molecular transport and signaling functions, suppressed d -galactose-induced harmful bacteria proliferation and galactose metabolism, and increased dopamine, glutamic acid, γ-aminobutyric acid, glutamine, tryptophan, N -acetylneuraminic acid, and nicotinamide levels. Overall, BNMS2 mitigated neural damage, oxidative stress, and inflammation by enhancing butyric acid production, modulating gut microbiota, and synergistically increasing cognitive-related metabolites, thereby mitigating cognitive dysfunction.