滇黄精水提物联合间歇性禁食通过调节肠道菌群改善高脂饮食诱导的小鼠肥胖及肝损伤

Polygonatum kingianum Coll.et Hemsl water extracts combined withintermittent fasting alleviates high fat diet-induced obesity and liverinjury by modulating gut microbiome

为探究我国著名食药两用滇黄精(Polygonatum kingianum Coll.et Hemsl,PK)水提物联合间歇性禁食对高脂饮食诱导小鼠肥胖、肝损伤及肠道微生态紊乱的预防保护作用及生物机制。通过分光光度法测定滇黄精水提物多糖含量为69.71%,总酚含量为5.4%。采用高通量液相质谱代谢组学技术定性解析滇黄精水提物化学成分,共检出325种代谢物,富含棉子糖、水苏糖、异麦芽糖等功能性低聚糖,γ-氨基丁酸、精氨酸、色氨酸等氨基酸类,以及甜菜碱等益生活性物质。8周龄健康雄性C57BL/6 J小鼠(n=60)分为正常饮食对照组(NC)、正常饮食+滇黄精干预组(NC+PK)、正常饮食+滇黄精联合间歇性禁食干预组(NC+PK+IF)、高脂饮食对照组(HF)、高脂饮食+滇黄精干预组(HF+PK)、高脂饮食+滇黄精联合间歇性禁食干预组(HF+PK+IF),开展8周干预。结果显示滇黄精干预(PK)和滇黄精联合间歇性禁食干预(PK+IF)可有效预防高脂诱导小鼠肥胖,显著改善葡萄糖耐受力和肝脏中超氧化物歧化酶活力,降低血清总甘油三酯含量和氧化应激水平,有效缓解由高脂诱发的肝脏细胞变性和脂质积累异常。滇黄精的摄入显著升高高脂小鼠粪便中拟杆菌门和变形菌门含量,降低厚壁菌门与拟杆菌门丰度比值。在属水平上,PK和PK+IF可有效降低高脂上调的梭状芽胞杆菌属、大肠杆菌、志贺菌、不动杆菌和胃瘤球菌属等与肥胖、肝脏脂质异常积累和损伤相关的菌属;相反,PK和PK+IF升高促产短链脂肪酸的拟普雷沃菌属、普雷沃菌属、丁酸弧菌属和双歧杆菌属。典型相关分析建立高脂诱导肥胖小鼠体重、葡萄糖耐受量、血脂和氧化应激水平改善作用,与肠道微生物之间的紧密关联。综上,滇黄精水提物富含多种益生营养物质,联合间歇性禁食通过改变高脂喂养肠道菌群结构,改善糖脂代谢水平和氧化应激状态,对高脂饮食诱导的小鼠肥胖及肝脏损伤等代谢紊乱问题产生积极影响。

The aim of this study was to investigate the effect of water extract from Polygonatum kingianum Coll.et Hemsl(PK)combined with intermittent fasting(IF)on preventing abnormal weight gain and hepatic steatosis in mice with high fat diet by modulating gut microbiota.PK contained 69.71%total polysaccharide and 5.4%total polyphenols.A total of 325 metabolites was detected by using liquid chromatograph-mass spectrometer based metabolomics,mainly including prebiotic oligosaccharides(e.g.raffinose,stachyose and isomaltose),amino acids(e.g.γ-aminobutyric acid,arginine,tryptophan and serine),and other compounds showing health-promoting effects,(e.g.betaine).The 8-week-old(n=60)healthy male C57BL/6J mice were randomly assigned into 6 groups:normal chow(NC),NC with oral administration of PK(NC+PK),NC with oral administration of PK and intermittent fasting(NC+PK+IF),high fat diet(HF),HF+PK and HF+PK+IF,respectively.During the intervention of 8 weeks,PK and PK+IF effectively prevented high-fat-induced abnormal weight gain,improved glucose tolerance and superoxide dismutase activity in liver,reduced serum triglycerides,and alleviated HF-induced liver cell degeneration and abnormal lipid accumulation.Moreover,PK significantly increased relative abundance of Bacteroidetes and decreased the ratio of Firmicutes to Bacteroidetes.Both PK and PK+IF intervention inhibited HF-induced upregulation in Clostridium,Escherichia-Shigella,Acinetobacter,and Ruminococcus at genus level,of which have been associated with obesity,excessive lipid accumulation and liver damage;conversely,PK and PK+IF elevated short-chain fatty acid-promoting genera,i.e.Alloprevotella,Prevotella,Butyrivibrio,and Bifidobacterium.PK-induced improvements in body weight,glucose tolerance,lipid metabolism and oxidative stress were strongly correlated with PK-altered gut microbiota.In conclusion,P.kingianum water extract rich in various probiotic substances and could beneficially prevent HF-induced obesity and liver damage by modulating gut microbiota.