A High‐Tryptophan Diet Alleviated Cognitive Impairment and Neuroinflammation in APP/PS1 Mice through Activating Aryl Hydrocarbon Receptor via the Regulation of Gut Microbiota

Scope Recent studies have highlighted the vital role of gut microbiota in the pathogenesis of Alzheimer's disease (AD). However, the effect of the regulation of gut microbiota by dietary components on AD remains unknown. Thus, the study explored that a high‐tryptophan (Trp) diet alleviates cognitive impairment by regulating microbiota. Methods and results Male APP/PS1 mice are fed 0.5% Trp diet for 4 weeks, and then cognitive function, amyloid‐β (Aβ) deposition, microglial activation, proinflammatory cytokines production, and gut microbiota are detected. Moreover, the level of aryl hydrocarbon receptor (AhR) and NF‐κB pathway related protein are determined. The results show that high‐Trp diet significantly alleviates cognitive impairment and Aβ deposits. Moreover, high‐Trp diet significantly inhibits activation of microglia, decreases the level of cluster of differentiation 11b (CD11b), and restrains the activation markers of microglia, such as cyclooxygenase‐2 (Cox‐2), interleukin (IL)‐1β, and IL‐6. Notably, high‐Trp diet significantly activates AhR, inhibits the phosphorylation of p65, and improves microbiota dysbiosis. Conclusions These findings demonstrated that high‐Trp diet exerts anti‐inflammatory effects via upregulating AhR and suppressing NF‐κB pathway, and its mechanisms may be mediated by regulating gut microbiota, suggesting that Trp diet may be a potential strategy for AD intervention.