Abstract
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a growing health concern worldwide. Administration of probiotics and prebiotics has been proposed as a convenient and effective treatment. Our study aims to evaluate the therapeutic benefits of Lactobacillus paracasei N1115 (N1115) and fructooligosaccharides (FOS) by examining the histopathogenesis and underlying molecular events of NAFLD. MATERIAL AND METHODS: An NAFLD mouse model was established by feeding C57BL/6 mice with a high-fat diet (HFD). N1115, FOS and synbiotics were administered for 16 weeks. RESULTS: N1115, FOS and synbiotics alleviated HFD-induced hepatic steato-sis and release of tumor necrosis factor-α, and slowed the progression of cirrhosis. Compared to the HFD group, these dietary supplements reduced serum total triglyceride and cholesterol, and appeared to decrease the fasting blood glucose and insulin. Intraperitoneal glucose tolerance tests, homeostatic model assessment of insulin resistance and real-time PCR showed that the regimens could overcome insulin resistance. These findings were associated with the transcriptional repression of inflammatory factors such as lipopolysaccharides, Toll-like receptor 4 and nuclear factor-κB. Lastly, N1115, FOS, and synbiotics improved the intestinal barrier functions and histologic integrity. This was accompanied by the restoration of the p38 MAPK pathway and in-creased expression of the tight junction components occludin-1 and claudin-1. CONCLUSIONS: N1115, FOS and synbiotics are effective in the prevention and treatment of NAFLD. Our data support the translation of these agents into clinical evaluation in human subjects with NAFLD and/or associated risk factors.