PAYCS Alleviates Scopolamine-Induced Memory Deficits in Mice by Reducing Oxidative and Inflammatory Stress and Modulation of Gut Microbiota-Fecal Metabolites-Brain Neurotransmitter Axis

The bioactive peptide PAYCS (Pro-Ala-Tyr-Cys-Ser) identified from anchovy hydrolysates has been reported to be positive in memory alleviation. The gut microbiota-brain axis plays a vital role in brain functions, which could be affected by nutritional supplementation. Herein, we found that PAYCS at different concentrations (PAYCS-L and PAYCS-H) showed various improving effects in behavioral tests and alleviation effects on oxidative as well as inflammatory stress in the scopolamine-induced AD mouse model. The 16S rRNA results illustrated that PAYCS-L altered the ratio of Bacteroidetes/Firmicutes and PAYCS treatment elevated the relative abundance of Cacteroidaceae and Prevotellaceae. Notably, administration of PAYCS significantly upregulated memory-related metabolites and neurotransmitters. Overall, PAYCS-L reversed memory deficits of amnesiac mice partially via the modulation of gut microbiota-metabolites-brain neurotransmitter axis. For PAYCS-H, functions might be involved in the reversal of oxidative and inflammatory impairments in the liver and serum, which was also associated with the changed intestinal microbiota and fecal metabolites.