Abstract: In this study, three common seed coat gums, namely flaxseed gum (FG), Artemisia sphaerocephala Krasch. gum (ASKG), and chia seed gum (CSG), were selected to enzymatically prepare oligosaccharides. The potential mechanism by which seed coat gum oligosaccharides alleviate Alzheimer’s disease (AD) in a Drosophila model of AD was explored through molecular structure characterization combined with gut microbiota analysis and untargeted metabolomics. The results showed that all three seed coat gums and their oligosaccharides improved the climbing ability, extended the lifespan of AD Drosophila, and significantly reduced the levels of amyloid β42 (Aβ42), cyclic adenosine monophosphate (cAMP), and acetylcholinesterase (AchE) in the Drosophila brain, with CSG and CSG oligosaccharides (CSGOS) being the most effective. 16S rDNA sequencing showed that CSGOS had a significant proliferative effect on beneficial bacteria such as Lactobacillus and Leuconostoc, while inhibiting the proliferation of harmful bacteria such as Serratia and Enterococcus. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of metabolites showed that the CSG and CSGOS affected the progression of AD mainly through metabolic pathways such as purine metabolism, pyrimidine metabolism, and amino acid biosynthesis. In conclusion, FG, ASKG, CSG, and their oligosaccharides can significantly alleviate AD in Drosophila, the most effective being CSG and its oligosaccharides.

Key words: seed coat gum; oligosaccharide; Alzheimer’s disease; Drosophila melanogaster; gut microbiota; metabolomics