Yan Liu,Zhangtie Wang,Yansong Zhang,Tian Zhao,Qingjun Zhang,Weisu Huang,Baiyi Lu
Dietary cholesterol is often found in a high-fat diet (HFD) and excessive intake is harmful to cognitive function. The gut microbiome constitutes an environmental factor influenced by diet, which regulates cognitive function via the gut-brain axis. The present study explored the role of dietary cholesterol in HFD-induced cognitive impairment and the participation of the gut microbiota and metabolites. Here, we found that dietary cholesterol promoted cognitive impairment in HFD-fed mice, which was associated with an increase in gut microbiota containing 7α-dehydroxylase, including Lachnospiraceae bacterium, Dorea sp. Clostridium sp. and elevated levels of deoxycholic acid (DCA) in the hippocampus. Upon dietary cholesterol intake, the activity of gut microbiota in mice to produce DCA is increased. Fecal microbiota transplantation confirmed that the cognitive impairment-promoting process was driven by gut microbiota. Reducing circulating bile acid levels with cholestyramine improved cognitive decline in mice, whereas hippocampal administration of DCA worsened cognitive function. Pharmacological inhibition of hippocampal apical sodium bile acid transporter reduces neuronal DCA accumulation and improves neuronal apoptosis as well as cognitive impairments in mice. Overall, this study revealed that dietary cholesterol promotes HFD-induced cognitive impairment by inducing the production of DCA through gut microbiota metabolism.
Yongshuai Jing,Dongbo Liu,Yuwei Zhang,Shilin Zhang,Beibei Hu,Yinghua Xie,Zhiwei Li
A polysaccharide (PSMP2) was isolated from Salvia miltiorrhiza , and its sulfated derivative (PSMP2-S) was synthesized. The chemical structures of PSMP2 and PSMP2-S were analyzed by various chemical analysis methods and instrumental analysis methods. The ultrastructures and thermal stability were further investigated. In addition, PSMP2 and PSMP2-S had strong immunomodulatory activity and could regulate cytokines (interleukin-2, interleukin-6 and tumor necrosis factor-α), increased the content of short chain fatty acids and effectively reduced the relative abundance of Bacteroides and increased the relative abundance of Firmicutes , significantly increase Muribaculaceae and Lactobacillaceae , and inhibit Lachnospiraceae and Ruminococcaceae , improve the composition of gut microbiota. This study showed that PSMP2 and PSMP2-S might be used as potential natural immune regulators and gut microbiota regulators, and had great development value in the field of food and medicine.
Autophagy is pivotal for the management of intestinal homeostasis, modulation of intestinal immunity response and anti-microbial protection. Previous studies have documented the protective function of Polygonatum cyrtonema Saponin (PCS) against intestinal injury, but whether PCS modulated autophagy and its associated responses remained unknown. A model of dextran sodium sulfate (DSS)- elicited intestinal injury was employed to confirm this hypothesis. The results showed that PCS effectively relieved the typical symptoms of DSS-induced weight reduction, shortened colon length, and augmented disease activity index score, down-regulated organ indices, reduced hepatic oxidative stress, and inhibited excessive inflammatory mediators. Meanwhile, PCS intervention ameliorated the intestinal barrier dysfunction via promoting the differentiation of goblet cells and augmenting the expression of tight junction proteins (TJs). It also suppressed apoptosis in intestinal cells by altering the Bcl-2/Bax ratios and diminishing the expressions of Caspase-9 and Caspase-3. Additionally, PCS remarkably enhanced autophagy by modulating the PI3K/AKT/mTOR signal pathway. More importantly, the classical autophagy inducer rapamycin augmented the beneficial effects of PCS. In contrast, the autophagy inhibitor 3-methyladenine essentially eliminated the above effects, revealing a role for autophagy in the response. Further studies have demonstrated that PCS intervention improved the diversities of the intestinal flora, increased occupancy of beneficial bacteria in Lachnospiraceaeae and Akkermansia , which was closely associated with autophagy. Taken together, these findings demonstrated that PCS is a potential supplier of prebiotics by modulating immunity, repairing intestinal mucosal injury, regulating autophagy and intestinal flora, and autophagy is a key target for PCS-mediated intestinal barrier protection.
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