Li_2025_J.Alzheimers.Dis__13872877251339762

BackgroundNo effective drug treatment is currently available for Alzheimer's disease (AD), highlighting the urgent need to develop efficient therapeutic options. We have developed a formula based on medicine and food homology (MFH) consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN), and demonstrated that it can treat AD by alleviating neuroinflammation and oxidative stress. However, whether EPRCN can improve AD by regulating gut microbiota remains unknown.ObjectiveThe current study aimed to evaluate the effect of EPRCN on regulating gut microbiota and neuroprotection.Methods16S rRNA sequencing was used to assess the structure of gut microbiota. Hematoxylin-eosin (HE) staining, qRT-PCR, and ELISA were used to evaluate gut inflammation. Detected indexes associated with cholinergic dysfunction and neuronal damage to investigate the neuroprotective effects of EPRCN.Results16S rRNA gene analysis revealed that EPRCN remodeled the gut microbiota, inhibited gut metabolic disorders, and promoted CoA biosynthesis in scopolamine-induced mice. EPRCN can ameliorates gut inflammation by activating the cholinergic anti-inflammatory pathway. The results further indicated that EPRCN improved cholinergic dysfunction by inhibiting the activity of acetylcholinesterase and restoring cholinergic receptors. Additionally, EPRCN administration suppressed the neuronal loss and elevated brain derived neurotrophic factor expression in hippocampus. Correlation analysis found that alteration of several gut microbes was associated with indexes improved by EPRCN.ConclusionsThese findings suggest that EPRCN may serve as a promising dietary intervention for treating AD by regulating the microbiota-gut-brain axis and exerting neuroprotective function.