Oat peptide ameliorates cognitive impairment via mediating gut-brain axis in mice: A multi-omics approach

Oat protein-derived bioactive peptide (RW-9) has been reported to exert beneficial effects in memory deficits. However, the mechanisms underline the neuroprotective effects of RW-9 peptide against Alzheimer disease (AD) like symptoms remain unclear. In this study, we found that RW-9 intervention showed various improving effects in cognitive-behavioral tests and alleviated the oxidative stress and inflammation in scopolamine-induced mice model. The H&E staining results demonstrated the protective effects of RW-9 on hippocampal neurons. Proteomic analysis of hippocampus revealed the upregulation of memory related proteins, including Grin3a, Ppp2r1b, Stat6, Pik3cd, Slc5a7, Chrm2 mainly involved in cAMP signaling, PI3K-Akt signaling, and JAK-STAT signaling pathways. The administration of RW-9 significantly upregulated the neurotransmitters including Serotonin (5-HT), Dopamine (DA), and Arginine (Arg) in mice brain. In addition, it modulated the serum metabolic profile and increased the expression levels of ATP-binding cassette (ABC) transporters, biosynthesis of amino acids, and Amino acyl-tRNA biosynthesis among others. Furthermore, 16s-rRNA results illustrated that the RW-9 restored the abundance of Muribaculaceae, Lachnospiraceae , Lactobacillus, Clostridia and Bactericides . Consistently, RW-9 restored the levels of SCFAs. Taken together, our results suggest that the RW-9 may prevent the AD like symptoms via modulation of gut-serum-brain axis. • Oat peptide (RW-9) exhibit a positive effect on ameliorating learning and memory impairment in mice. • RW-9 neuroprotective mechanisms effectively included inhibiting scopolamine-induced oxidative stress and inflammation. • RW-9 is a potential therapeutic for preventing and mitigating AD-like symptoms, possibly via gut-brain axis modulation.