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桔梗多糖通过靶向肠道微生物群减轻高脂饮食诱导的小鼠肥胖。

Polysaccharides from Platycodon grandiflorus attenuates high-fat diet induced obesity in mice through targeting gut microbiota.

作者信息

Ke Weixin, Flay Kate Jade, Huang Xiaoning, Hu Xiaosong, Chen Fang, Li Chunbao, Yang Dan Aaron

机构信息

College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China; National Center of Meat Quality and Safety Control, Nanjing 210095, China; National Key Laboratory of Meat Quality Control and New Resource, Nanjing Agricultural University, Nanjing 210095, China.

Department of Veterinary Clinical Sciences, City University of Hong Kong, Kowloon 999077, Hong Kong Special Administrative Region of China.

出版信息

Biomed Pharmacother. 2023 Oct;166:115318. doi: 10.1016/j.biopha.2023.115318. Epub 2023 Aug 10.

DOI:10.1016/j.biopha.2023.115318
PMID:37572640
Abstract

The root of Platycodon grandiflorus (PG), abundant in soluble polysaccharides, has a long history in traditional Asian diets and herbal medicine due to its anti-inflammatory activity and anti-obesity effects. Our previous study was the first to establish a link between the beneficial effects of PG and changes in the gut microbiota, and suggested potential roles that the polysaccharide components play. However, more evidence was needed to understand the anti-obesity functions of polysaccharides from PG (PS) and their relationship with the regulation of the gut microbiota. In this study, we first performed an experiment to explore the anti-obesity activities of PS: Male C57BL/6 mice (six-weeks-old) were fed either a standard control diet (CON), or a high-fat diet (HFD) to induce obesity, or a HFD supplemented with PS (HFPS) for 8 weeks. Body weight and food intake were monitored throughout. Lipid metabolism were determined and related gene expression changes in adipose tissues were analyzed by RNA-seq. Amplicon sequencing of the bacterial 16 S rRNA gene was used to explore gut microbiota structure in fecal samples. Then, we performed the second experiment to explore whether the anti-obesity activities of PS were dependent on the regulation of the gut microbiota: Male C57BL/6 mice (six-weeks-old), treated with an antibiotic cocktail to reduce the gut microbial load, were fed either a HFD (A-HFD) or a HFPS (A-HFPS) diet for 8 weeks. Finally, we used in vitro fermentation experiments to verify the effects of PS on the growth and metabolic activities of the gut microbes. We found that PS significantly reduced HFD-induced weight gain and excessive fat accumulation, changed the expression of key genes involved in lipid metabolism, and attenuated HFD-induced changes in the gut microbiota. However, PS did not affect fat accumulation or lipid metabolism in the gut microbiota depleted mice. Overall, our results show that PS has significant effects on the gut microbiota in the mouse model, and the anti-obesity effects of PS are mediated via changes in the gut microbiota composition and metabolic activity.

摘要

桔梗(PG)的根部富含可溶性多糖,由于其抗炎活性和抗肥胖作用,在亚洲传统饮食和草药中有着悠久的历史。我们之前的研究首次建立了PG的有益作用与肠道微生物群变化之间的联系,并提出了多糖成分所起的潜在作用。然而,需要更多证据来了解PG多糖(PS)的抗肥胖功能及其与肠道微生物群调节的关系。在本研究中,我们首先进行了一项实验来探索PS的抗肥胖活性:将六周龄的雄性C57BL/6小鼠分为三组,分别喂食标准对照饮食(CON)、诱导肥胖的高脂饮食(HFD)或添加PS的高脂饮食(HFPS),持续8周。全程监测体重和食物摄入量。测定脂质代谢情况,并通过RNA测序分析脂肪组织中相关基因表达的变化。利用细菌16S rRNA基因的扩增子测序来探究粪便样本中的肠道微生物群结构。然后,我们进行了第二项实验,以探究PS的抗肥胖活性是否依赖于肠道微生物群的调节:用抗生素混合物处理以降低肠道微生物负荷的六周龄雄性C57BL/6小鼠,分别喂食HFD(A-HFD)或HFPS(A-HFPS)饮食8周。最后,我们通过体外发酵实验来验证PS对肠道微生物生长和代谢活性的影响。我们发现,PS显著降低了HFD诱导的体重增加和过多的脂肪堆积,改变了参与脂质代谢的关键基因的表达,并减弱了HFD诱导的肠道微生物群变化。然而,PS对肠道微生物群耗竭的小鼠的脂肪堆积或脂质代谢没有影响。总体而言,我们的结果表明,PS在小鼠模型中对肠道微生物群有显著影响,并且PS的抗肥胖作用是通过肠道微生物群组成和代谢活性的变化介导的。

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