Water extract of goji berries improves neuroinflammation induced by a high-fat and high-fructose diet based on the bile acid-mediated gut–brain axis pathway

The high-fat and high-fructose diet (HFFD) is a common diet in westernized societies, which worsens disturbances in gut microbiota and bile acid (BA) metabolism. Herein, the present study aimed to investigate the effects of the water extract of Lycium barbarum fruits (LBE) on gut microbiota and BA metabolism in mice with HFFD-induced neuroinflammation. The results showed that supplementation of LBE for 14 weeks remarkably ameliorated weight gain and insulin resistance and suppressed microglial activation and neural neuroinflammation induced by HFFD. The results of Morris water maze and Y-maze tests demonstrated that LBE attenuated HFFD-induced cognitive impairment. Moreover, LBE elevated hepatic BA biosynthesis and excretion of BAs and increased elimination of BAs via the feces. Notably, LBE supplementation resulted in the enrichment of tauroursodeoxycholic acid in the cortex and hippocampus. Furthermore, the 16S rDNA sequencing results showed that LBE could modulate the structure of gut microbiota, and in the meantime decrease the relative abundance of Clostridium_XlVa, which is associated with BA homeostasis. Additionally, LBE exerted neuroprotective effects involving the increment of Lactococcus, known as a potentially beneficial bacterium. These results demonstrated that LBE could ameliorate neuroinflammation and cognitive impairment in HFFD-induced mice through the gut-liver-brain axis, which might be due to the regulation of BA homeostasis and gut microbiota in mice.