微塑料和高脂饮食暴露对小鼠非酒精性脂肪肝病的影响:肠道菌群与代谢组学研究
Impact of Microplastic and High-Fat Diet Exposure on Non-Alcoholic Fatty Liver Disease in Mice: A Study of Gut Microbiota and Metabolomics
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摘要: 非酒精性脂肪肝病(NAFLD)是全球最常见的慢性肝病之一,与环境因素相关。本研究探讨了聚苯乙烯微塑料(PS)与高脂饲料(HFD)联合作用对NAFLD进展的影响,旨在揭示PS在NAFLD发生中的作用,对理解NAFLD的环境诱因具有重要意义。48只雄性C57BL/6J小鼠随机分为4组:空白对照组、HFD组、PS暴露组、HFD+PS联合组,连续处理8周。通过监测小鼠体质量、血糖、口服糖耐量测试(OGTT)、胰岛素耐量测试(ITT),并检测血清生化指标,评估肝脏和肠道组织病理学变化;同时,采用16S rRNA高通量测序分析肠道微生物群结构变化,以及进行代谢组学分析。研究发现,HFD+PS组小鼠体质量增长最快,血糖波动显著,血脂异常加剧。病理学结果显示肠道黏膜损伤和肝脏脂质沉积增加。肠道微生物群结构分析表明,HFD和PS联合作用导致肠道菌群多样性降低,厚壁菌门与拟杆菌门比值升高,有益菌减少,有害菌增加。代谢组学分析显示,甘油磷脂代谢显著变化,磷脂酰胆碱(PC)水平上升且溶血磷脂酰胆碱(LysoPC)水平下降。研究表明,PS和HFD联合作用可显著加剧NAFLD的进展,其作用机制可能涉及肠道菌群紊乱和甘油磷脂代谢的紊乱。本研究为理解PS在NAFLD中的作用提供了新的见解,提示环境污染和不健康饮食可能对人类健康产生潜在的协同影响。Abstract: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases globally, associated with environmental factors. This study explored the impact of polystyrene microplastics (PS) exposure in combination with a high-fat diet (HFD) on the progression of NAFLD, aiming to elucidate the role of PS in the occurrence of NAFLD, which is of significant importance for understanding the environmental triggers of NAFLD. Forty-eight male C57BL/6J mice were randomly divided into four groups: a control group, a high-fat diet (HFD) group, a PS exposure group, and a combined HFD+PS exposure group, and were treated continuously for 8 weeks. Mouse weight, blood glucose, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were monitored, and serum biochemical indices were detected to assess pathological changes in liver and intestinal tissues. Additionally, the structure of the gut microbiota was analyzed using 16S rRNA high-throughput sequencing, and metabolomic analysis was conducted. The study found that mice in the HFD+PS group gained weight most rapidly, exhibited significant blood glucose fluctuations, and had exacerbated dyslipidemia. Pathological results showed increased intestinal mucosal damage and hepatic lipid deposition. Analysis of the gut microbiota structure revealed that the combined action of HFD and PS led to reduced gut microbial diversity, an increased ratio of Firmicutes to Bacteroidetes, a decrease in beneficial bacteria, and an increase in harmful bacteria. Metabolomic analysis showed significant changes in glycerophospholipid metabolism, with elevated levels of phosphatidylcholine (PC) and decreased levels of lysophosphatidylcholine (LysoPC). The study demonstrated that the co-action of PS and HFD can significantly exacerbate the progression of NAFLD, and the underlying mechanisms may involve disruptions in gut microbiota and perturbations in glycerophospholipid metabolism. This study provides new insights into the role of PS in NAFLD, suggesting that environmental pollution and unhealthy diets may have potential synergistic effects on human health.
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Key words:
- polystyrene microplastics /
- high-fat diet /
- mice /
- gut microbiota /
- glycerophospholipid metabolism
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