Aloe polysaccharides ameliorate obesity-associated cognitive dysfunction in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity.

Aloe polysaccharides (APs) display cognition-improving properties, but the underlying mechanisms remain unclear. Herein, AP supplementation for 24 weeks significantly improved cognitive behavioral disturbances caused by a high-fat diet. Moreover, APs notably reshaped the structure of the gut microbiota, which was manifested by increasing the relative abundance of Alloprevotella , Alistipes , Romboutsia , Turicibacter , Prevotellaceae_UCG-001 , and Akkermansia while reducing the abundance of Parasutterella , Staphylococcus , Helicobacter , Enterococcus , and Erysipelatoclostridium . Notably, the gut barrier damage and LPS leakage caused by HF were recovered by APs. Additionally, with the improvement of intestinal barrier integrity, oxidative stress and inflammation in the brain and jejunum were significantly ameliorated. Furthermore, the expression of genes associated with cognitive impairment and the intestinal tract barrier was up-regulated ( CREB, BDNF , TrkB , ZO-1 and occludin ), while the expression of genes associated with inflammatory factors was down-regulated ( IL-1β , IL-6 , and TNF-α ). Finally, we observed a significant correlation among cognition-related genes, gut microbiota, oxidative stress, and inflammation in the HF-AP group. Together, our findings suggest that altered gut microbiota composition and improved gut barrier integrity may be important targets for potentially improving high-fat diet-induced cognitive impairment.