The Improvement Effects of Sika Deer Antler Protein in an Alzheimer's Disease Mouse Model via the Microbe–Gut–Brain Axis

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. The interplay between the intestinal microbiota and metabolites is believed to influence brain function and the pathogenesis of neurodegenerative conditions through the microbe–gut–brain axis. Sika deer antler protein possesses neuroprotective properties; however, the precise mechanism by which it improves AD remains unclear. Sika deer antler protein ameliorated AD in vivo by activating the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathway. The metabolome of brain and intestinal tissues and the microbiota of intestinal contents were tested and analyzed according to the microbe‐gut‐brain theory. Sika deer antler protein increased beneficial bacterial levels and decreased harmful bacterial levels. Correlation analyses using the gut flora–metabolomics pathway ultimately revealed that sika deer antler protein modulated the brain and intestinal tract bi‐directionally via the tyrosine metabolism pathway, thereby establishing a connection within the microbe–gut–brain axis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the differential metabolite targets of the DAP4 group showed that the enriched pathways mainly included PI3K/AKT, which was consistent with the findings of the pharmacodynamic mechanisms observed in in vivo experiments. This suggests that antler protein may be involved in microbe‐gut‐brain interactions through tyrosine metabolism and may improve AD by activating the PI3K/AKT/Nrf2 signaling pathway. These findings add to our understanding of the microbe–gut–brain axis facilitated by sika deer antler protein and offer novel insights for further research on sika deer antler protein in alleviating AD.