桑椹醇提取物对高脂饮食小鼠肠道菌群结构与脂代谢异常的改善作用

Ameliorating Effects of Mulberry Fruit Ethanol Extract on the Gut Microbiota Composition and Abnormal Lipid Metabolism of High-Fat Diet-Induced Mice

桑椹是一种药用食品,广泛用于中药治疗高脂血症。为了探索桑椹的抗高脂血症作用,以及对肠道菌群的调节方式,将ICR小鼠随机分为4组,包括正常饮食组(NCD)、正常饮食+桑椹醇提取物组(NCD+MFE)、高脂饮食组(HFD)和高脂饮食+桑椹醇提取物组(HFD+MFE),分别灌胃给药28 d后,采用试剂盒或实时荧光定量PCR检测血清和肝脏的脂质、葡萄糖水平,以及抗氧化酶和肝脏损伤等指标,并采用16S rRNA基因测序法分析各组小鼠的肠道菌群变化。研究结果显示,口服MFE对NCD小鼠的体质量和血糖没有影响,但显著降低HFD诱导的高脂血症小鼠的体质量及脂肪质量。MFE显著降低了NCD和HFD喂养小鼠的血清总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-c)水平,并显著增强了多种抗氧化酶的表达和活性。MFE治疗还显著减轻HFD诱导的肝脏脂肪变性和损害。宏基因组分析显示,口服MFE显著改变了肠道微生物群的结构,特别是提高了产丁酸菌Clostridium_XIVb的相对丰度。相关分析表明,Clostridium_XIVb的富集与血清/肝脏脂质沉积呈显著负相关,与抗氧化酶水平提高呈正相关。总之,MFE有潜力发展成为益生元或膳食补充剂,以预防HFD引起的高脂血症。同时,Clostridium_XIVb的富集可能在MFE抗高脂血症作用中起重要作用。

Mulberry fruit is a medical food and is widely used in Traditional Chinese medicines(TCMs)to ameliorate hyperlipidemia.To investigate the anti-hyperlipidemic effect and modulation on gut microbiota of mulberry fruit,we divided ICR mice into four groups,including normal-chow diet(NCD)group,NCD+mulberry fruit ethanol extract(MFE)group,high-fat diet(HFD)group and HFD+MFE group,and took oral administration with MFE for 28 d.Serum and liver indicators for lipids/glucose levels,antioxidant enzyme and liver damage were assessed by specific kit or real-time reverse transcription quantitative polymerase chain reaction(RT-qPCR).The alteration of gut microbiota was analyzed by 16S rRNA gene sequencing.Oral administration of MFE showed no influence on body weight and blood glucose in NCD mice,but markedly decreased body and fat weights of HFD-induced hyperlipidemic mice.MFE significantly decreased serum levels of total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-c)in both NCD and HFD-fed mice along with obviously increased expression and activity of multiple antioxidant enzymes.Treatment with MFE also remarkably alleviated HFD-induced liver steatosis and damage.Metagenomic analysis revealed that oral administration of MFE significantly shifted the structure of gut microbiota and especially enriched the relative abundance of butyrate-producer Clostridium_XIVb.Correlation analysis showed that the enrichment of Clostridium_XiVb was significantly negative to serum/liver lipids deposition and positive to the increase of anti-oxidative enzymes.In conclusion,MFE had a potential to develop into prebiotics or dietary supplement to protect against HFD-induced hyperlipidemia.The enrichment of Clostridium_XIVb may play an important role in anti-hyperlipidemic effect of MFE.