Prebiotic-Based Nanoamorphous Atorvastatin Attenuates Nonalcoholic Fatty Liver Disease by Retrieving Gut and Liver Health

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial and composite, with the disorder of lipid metabolism-induced lipotoxicity being one of the main risk factors. Atorvastatin (AT), the most widely prescribed lipid-lowering drug, has pleiotropic actions benefiting NAFLD treatment. However, low absorption rate in the gut and potential disruption of AT on gut flora hindered its further applications. Notably, gut dysbiosis is involved in and is thus a promising management strategy for NAFLD. In this study, we constructed a prebiotic-based AT nanoamorphous (PANA) to improve the efficacy of AT against NAFLD by retrieving liver and gut health. After oral administration, PANA showed superior drug accumulation in the liver tissue compared with pure AT. Moreover, PANA intervention effectively restored gut healthiness, indicated by reconstructed gut flora, and improved intestinal immunity, barrier integrity, and inflammation. Consequently, compared with AT, PANA treatment caused profound inhibition of weight gain and fat deposition, decreased plasma lipid levels, and alleviated hepatic steatosis and liver inflammation. The transcriptome analysis in the gut and liver tissues identified improved immunity and inflammation as potential mechanisms. This study suggests a promising strategy to treat NAFLD, assisted with nanotechnology in synergy with functional biomaterials.