Quinic Acid Suppresses on High-fat diet-induced Brain Oxidative Stress and Neuroinflammation via Regulating Gut Microbes Lactobacillus and Akkermansia

• Quinic acid inhibited HFD-induced brain oxidative stress and neuroinflammation • Lactobacillus and Akkermansia in HFD mice intestinal were regulated by quinic acid • Ablation of gut microbiota vanished the effects of quinic acid • Lactobacillus and Akkermansia transplantation restored the function of quinic acid Consumption of high-calorie diets is positively related to elevated risks of neurodegenerative diseases, and polyphenols-enriched diets showed opposite effects. Quinic acid is phenolic acid originating from plant-based foods, which possesses anti-oxidant, anti-inflammatory, and microbial regulation effects. In this study, we investigated the roles of gut microbiota in the regulation of quinic acid on high-fat diet (HFD)-induced brain oxidative stress and neuroinflammation. Results demonstrated that quinic acid intervention significantly alleviated brain oxidative stress and suppress neuroinflammation in the brains of HFD-induced mice. Analysis of gut microbiota revealed that Lactobacillus and Akkermansia were specifically altered during quinic acid intervention in HFD-fed mice and these alterations were negatively correlated with indicators of oxidative stress and inflammatory factors. Notably, when most gut microbiota were depleted via antibiotics treatment, quinic acid administration no longer alleviated brain oxidative stress and neuroinflammation. Conversely, transplantation of gut microbiota - or specifically Lactobacillus rhamnosus and Akkermansia muciniphila - into HFD-induced pseudo-germ-free mice reduced the brain oxidative stress and neuroinflammation of HFD mice. These foundings suggest that quinic acid suppresses HFD-induced brain oxidative stress and neuroinflammation by regulating Lactobacillus and Akkermansia . This study provides new insights into the development of microbiota-targeted functional foods with food bioactive ingredients.