低浓度微囊藻毒素-LR影响小鼠糖脂代谢的肠道微生物生态学机制研究

Previous studies have indicated that microcystins may cause metabolism disorder and induce a series of metabolic diseases including metabolic syndrome, obesity, diabetes mellitus, but the underlying mechanism remains unclear. The genetic diversity of gut microbiota and function provides a variety of key enzymes and biochemical metabolism pathways for the host metabolic process. In this research, from the point of view of gut microbial ecology, the impact of low concentration microcystins-LR on the carbohydrate and lipid metabolisms in mice will be systemically studied to explore their mechanisms through metabonomic and metagenomic analyses. The results of this research will explore the effects of low concentration microcystins exposure on carbohydrate and lipid metabolism and reveal the underlying molecular mechanisms which are helpful to assess the health risk of microcystins.

已有研究表明微囊藻毒素摄入可造成机体代谢过程紊乱，进而诱发代谢综合征、肥胖、糖尿病等代谢性疾病，但其中的致毒机理尚有待研究明确。肠道内微生物种群与功能基因的多样性，为宿主代谢过程提供了各种关键性酶和生化代谢通路。本项目拟通过小鼠暴露模型，从肠道微生物生态学角度出发，将高通量测序技术与代谢指标检测相结合，研究低浓度微囊藻毒素-LR暴露对小鼠肠道微生物群落结构和功能组成的影响，阐述藻毒素通过改变肠道微生物群落结构功能特征进而影响机体糖脂代谢的微生物生态学机制，为评估低浓度微囊藻毒素暴露的健康风险提供参考依据。

本项目通过构建小鼠暴露模型，建立小鼠肠道微生物群高通量检测方法，从生理生化与肠道微生物菌群变化等角度分析了低浓度藻类毒素对糖脂代谢过程的影响，完成了低浓度MC-LR暴露下小鼠肠道菌群介导糖脂代谢紊乱的毒理学机理的初步探究。主要结论如下：（1）染毒组小鼠出现肝脏肿大，出现炎症和脂肪堆积现象，空腹血糖升高，糖耐量降低，TG、TC、HDL-C与LDL-C含量在血清与肝脏中含量变化显著，表明MC-LR暴露扰乱了小鼠机体糖脂代谢的平衡状态；（2）肠道微生物的多样性随着MC-LR染毒剂量上升而明显下降，菌群中厚壁菌门与拟杆菌门的比例失衡，肠道微生物功能基因分析结果显示多条能量代谢通路以及细菌内毒素的生物合成通路受到了MC-LR暴露影响；（3）机理研究推测低浓度MC-LR暴露对小鼠代谢的影响机制表现为激活PPAR信号转导通路。本项目研究为评估低浓度微囊藻毒素暴露的健康风险提供参考依据。