Multi-omics integration reveals the impact of mediterranean diet on hepatic metabolism and gut microbiota in mice with metabolic dysfunction-associated steatotic liver disease

作者：Zixuan Wang, Ge Chen, Xutong Sun, Jia Xiao, Lingling Kong, Shunshun Jiang, Tingting Xu, Meijiao Wang, Hong Zhao · 发表于：Frontiers in Nutrition · 年份：2025 · DOI：10.3389/fnut.2025.1644014 · 被引用次数：5 · 研究领域：Liver Disease Diagnosis and Treatment、Gut microbiota and health、Liver Diseases and Immunity

Objective To investigate the effects of the Mediterranean diet (MD) on hepatic metabolism and gut microbiota in mice with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods C57BL/6 mice were fed a high-fat diet for 12 weeks to induce MASLD, with normal chow (NC)-fed mice as controls. Post-modeling, MASLD mice were randomized into three groups: HF (continued high-fat diet), HF-NC (switched to normal chow), and HF-MD (switched to MD). After 18-week interventions, body/liver weights, serum liver enzymes (ALT, AST), hepatic glycolipid markers (glucose, TC, TG, IBIL, DBIL), inflammatory cytokines (IL-6, TNF-α; ELISA), and histopathology (H&E and Oil Red O staining) were analyzed. Gut microbiota (metagenomic sequencing) and short-chain fatty acids (SCFAs; targeted metabolomics) were profiled. Results High-fat diet induced MASLD features including obesity, increased abdominal fat mass, hepatic steatosis with lipid droplets, and inflammation. Both HF-NC and HF-MD groups exhibited reduced body weight, liver index, hepatic cytokines, serum enzymes, and improved glucolipid profiles vs. HF group ( p < 0.05), with histopathology confirming attenuated steatosis. HF-MD outperformed HF-NC in lowering ALT, AST, IL-6, and TNF-α ( p < 0.05). MASLD mice showed gut dysbiosis characterized by decreased diversity, elevated Alistipes, Helicobacter, Mucispirillum , and Chlamydia , reduced SCFAs, and increased branched-chain fatty acids (BCFAs) ( p <...