Caffeic acid prevents non-alcoholic fatty liver disease induced by a high-fat diet through gut microbiota modulation in mice

[Display omitted] •Caffeic acid reduces lipid accumulation in HFD-fed mice.•Caffeic acid supplementation affects biochemical markers of HFD-fed mice.•Caffeic acid regulates lipogenesis-related protein expression in HFD-fed mice.•Caffeic acid alleviates endotoxemia and the proinflammatory response in HFD-fed mice.•Caffeic acid attenuates gut microbiota dysbiosis in HFD-fed mice. Caffeic acid (CA) is derived from many plants and may have the ability to reduce hepatic lipid accumulation. The gut microbiota produces lipopolysaccharides and further influences hepatic lipid metabolism, and thus plays an important role in the development of nonalcoholic fatty liver disease (NAFLD). However, whether the beneficial effects of CA are associated with the gut microbiota remains unclear. The present study aimed to investigate the benefits of experimental treatment with CA on the gut microbiota and metabolic functions in a mouse model of NAFLD. In this study, C57BL/6J mice received a high-fat diet (HFD) for 8 weeks and were then fed a HFD supplemented with or without CA for another 8 weeks. HFD induced obesity and increased accumulation of intrahepatic lipids, serum biochemical parameters and gene expression related to lipid metabolism. Microbiota composition was determined via 16S rRNA sequencing, and analysis revealed that HFD led to dysbiosis, accompanied by endotoxemia and low-grade inflammation. CA reverted the imbalance in the gut microbiota and related lipopolysaccharide-mediated inflammation, thus inhibiting deregulation of lipid metabolism-related gene expression. Our results support the possibility that CA can be used as a therapeutic approach for obesity-associated NAFLD via its anti-inflammatory and prebiotic integrative response.