Potential anti-Alzheimer’s disease effect of defatted walnut powder through remodeling gut microbiota and modulating amino acid metabolite levels

Alzheimer’s disease (AD) is a major health challenge due to its high morbidity. This study aimed to investigate the potential effects of defatted walnut powder (DWP), which is the residue obtained after extracting oil from walnut kernels, on memory improvement. HPLC was used to establish the fingerprints of 14 batches of DWP extract (DWPE) obtained from various origins. Behavioral experiments and functional indicators were conducted to evaluate the efficacy of DWPE on AD. The results indicated that DWPE regulated the cholinergic system disorder in brain tissue. Additionally, DWPE reduced oxidative stress levels, neuroinflammation, and the damage of pyramidal cells in both the cortex and the hippocampal CA3 region. Subsequently, targeted amino acid metabolomics, gut microbiota sequencing and fecal microbiota transplantation confirmed that DWPE played a regulatory role in amino acid metabolism regulated by gut microbiota, effectively decreasing the levels of fat-soluble neurotoxic factor ammonia