Wang Zixuan, Chen Ge, Sun Xutong, Xiao Jia, Kong Lingling, Jiang Shunshun, Xu Tingting, Wang Meijiao, Zhao Hong
Qingdao Medical College of Qingdao University, Qingdao, China.
Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
Front Nutr. 2025 Aug 12;12:1644014. doi: 10.3389/fnut.2025.1644014. eCollection 2025.
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).
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.
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 ( < 0.05), with histopathology confirming attenuated steatosis. HF-MD outperformed HF-NC in lowering ALT, AST, IL-6, and TNF-α ( < 0.05). MASLD mice showed gut dysbiosis characterized by decreased diversity, elevated , and , reduced SCFAs, and increased branched-chain fatty acids (BCFAs) ( < 0.05). Both dietary interventions partially ameliorated gut dysbiosis in MASLD mice, with the HF-MD group uniquely enriching beneficial taxa including , and .
MD alleviates MASLD progression by synergistically improving hepatic metabolic homeostasis and gut microbiota composition, demonstrating superior efficacy over NC in mitigating inflammation, enriching beneficial microbes, and regulating microbial metabolism. These findings highlight MD's potential as a targeted dietary intervention for MASLD.
研究地中海饮食（MD）对代谢功能障碍相关脂肪性肝病（MASLD）小鼠肝脏代谢和肠道微生物群的影响。
将C57BL/6小鼠喂食高脂饮食12周以诱导MASLD，以正常饮食（NC）喂养的小鼠作为对照。建模后，将MASLD小鼠随机分为三组：HF（继续高脂饮食）、HF-NC（改为正常饮食）和HF-MD（改为MD）。经过18周的干预后，分析体重/肝脏重量、血清肝酶（ALT、AST）、肝脏糖脂标志物（葡萄糖、TC、TG、IBIL、DBIL）、炎性细胞因子（IL-6、TNF-α；酶联免疫吸附测定）和组织病理学（苏木精-伊红染色和油红O染色）。对肠道微生物群（宏基因组测序）和短链脂肪酸（SCFAs；靶向代谢组学）进行分析。
高脂饮食诱导了MASLD特征，包括肥胖、腹部脂肪量增加、伴有脂滴的肝脏脂肪变性和炎症。与HF组相比，HF-NC组和HF-MD组的体重、肝脏指数、肝脏细胞因子、血清酶均降低，糖脂谱改善（P<0.05），组织病理学证实脂肪变性减轻。HF-MD组在降低ALT、AST、IL-6和TNF-α方面优于HF-NC组（P<0.05）。MASLD小鼠表现出肠道生态失调，其特征为多样性降低、厚壁菌门和变形菌门升高、SCFAs减少以及支链脂肪酸（BCFAs）增加（P<0.05）。两种饮食干预均部分改善了MASLD小鼠的肠道生态失调，HF-MD组独特地富集了有益分类群，包括双歧杆菌属、阿克曼氏菌属和嗜黏蛋白阿克曼氏菌。
MD通过协同改善肝脏代谢稳态和肠道微生物群组成来减轻MASLD进展，在减轻炎症、富集有益微生物和调节微生物代谢方面显示出优于NC的疗效。这些发现突出了MD作为MASLD靶向饮食干预的潜力。
