食品与发酵工业 >

2022 , Vol. 48 >Issue 13: 91 - 102

DOI: https://doi.org/10.13995/j.cnki.11-1802/ts.029607

研究报告

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

  • 卫钰成 ,
  • 杨敏敏 ,
  • 施琳 ,
  • 刘天启 ,
  • 严淘 ,
  • 张妍 ,
  • 梁伊帆 ,
  • 周兰荠 ,
  • 邹家乐 ,
  • 张华峰
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  • 1(陕西师范大学 食品工程与营养科学学院,陕西 西安,710119)
    2(陕西师范大学 西北濒危药材资源开发国家工程实验室,陕西 西安,710119)
    3(陕西师范大学 中俄食品与健康科学国际联合研究中心,陕西 西安,710119)
    4(陕西师范大学 西安市特色水果贮藏与保鲜重点实验室,陕西 西安,710119)
第一作者：卫钰成本科生和杨敏敏硕士研究生为共同第一作者(施琳副研究员为通信作者,E-mail: linshi198808@snnu.edu.cn)

收稿日期: 2021-10-05

  修回日期: 2021-11-01

  网络出版日期: 2022-08-03

基金资助

中央高校基本科研业务费专项资金项目(GK202103096);陕西省高校科协青年人才托举计划项目(20210204);大学生创新创业训练计划项目(S202010718254)

收起

Polygonatum kingianum Coll. et Hemsl water extracts combined with intermittent fasting alleviates high fat diet-induced obesity and liver injury by modulating gut microbiome

  • WEI Yucheng ,
  • YANG Minmin ,
  • SHI Lin ,
  • LIU Tianqi ,
  • YAN Tao ,
  • ZHANG Yan ,
  • LIANG Yifan ,
  • ZHOU Lanqi ,
  • ZOU Jiale ,
  • ZHANG Huafeng
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  • 1(School of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an 710119, China)
    2(National Engineering Laboratory for Resources Development of Endangered Crude Drugs in Northwest China, Shaanxi Normal University, Xi’an 710119, China)
    3(International Joint Research Center of Shaanxi Province for Food and Health Sciences, Shaanxi Normal University, Xi’an 710119, China)
    4(Key Laboratory of Characteristic Fruit Storage and Preservation, Shaanxi Normal University, Xi’an 710119, China)

Received date: 2021-10-05

  Revised date: 2021-11-01

  Online published: 2022-08-03

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摘要

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。

关键词： 滇黄精; 间歇性禁食; 高脂饮食; 肠道菌群; 肝损伤

本文引用格式

卫钰成 , 杨敏敏 , 施琳 , 刘天启 , 严淘 , 张妍 , 梁伊帆 , 周兰荠 , 邹家乐 , 张华峰 . 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[J]. 食品与发酵工业, 2022 , 48(13) : 91 -102 . DOI: 10.13995/j.cnki.11-1802/ts.029607

Abstract

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.

Key words： Polygonatum kingianum Coll. et Hemsl; intermittent fasting; high fat diet; gut microbiota; liver injury

参考文献

[1] KATTA N, LOETHEN T, LAVIE C J, et al. Obesity and coronary heart disease:Epidemiology, pathology, and coronary artery imaging[J].Current Problems in Cardiology, 2021, 46(3):100655.
[2] YANG M M, YAN T, YU M, et al.Advances in understanding of health-promoting benefits of medicine and food homology using analysis of gut microbiota and metabolomics[J].Food Frontiers, 2020, 1(4):398-419.
[3] 王硕. 黄精的研究现状[J].农业科技通讯, 2020(1):46-47.
WANG S.Current status of research on Polygonatum sibiricum [J].Bulletin of Agricultural Science and Technology, 2020(1):46-47.
[4] 任洪民, 邓亚羚, 张金莲, 等.药用黄精炮制的历史沿革、化学成分及药理作用研究进展[J].中国中药杂志, 2020, 45(17):4 163-4 182.
REN H M, DENG Y L, ZHANG J L, et al.Research progress on processing history evolution, chemical components and pharmacological effects of Polygonati rhizoma[J].China Journal of Chinese Materia Medica, 2020, 45(17):4 163-4 182.
[5] ERDEM Y, ÖZKAN G, ULUSOY ş, et al.The effect of intermittent fasting on blood pressure variability in patients with newly diagnosed hypertension or prehypertension[J].Journal of the American Society of Hypertension, 2018, 12(1):42-49.
[6] GRAJOWER M M, HORNE B D.Clinical management of intermittent fasting in patients with diabetes mellitus[J].Nutrients, 2019, 11(4):873.
[7] MALINOWSKI B, ZALEWSKA K, WSIERSKA A, et al.Intermittent fasting in cardiovascular disorders-an overview[J].Nutrients, 2019, 11(3):673.
[8] LIN J, JIANG X X, DONG M, et al.Hepatokine pregnancy zone protein governs the diet-induced thermogenesis through activating brown adipose tissue[J].Advanced Science, 2021, 8(21):2101991.
[9] YIN C, LI Z H, XIANG Y L, et al.Effect of intermittent fasting on non-alcoholic fatty liver disease:Systematic review and meta-analysis[J].Frontiers in Nutrition, 2021, 8:709683.
[10] SHI H N,ZHANG B J,ABO-HAMZY T, et al.Restructuring the gut microbiota byintermittent fasting lowers blood pressure[J].Circulation research:a journal of the American Heart Association, 2021, 128(9):1 240-1 254.
[11] CIGNARELLA F, CANTONI C, GHEZZI L, et al.Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota[J].Cell Metabolism, 2018, 27(6):1 222-1 235.
[12] VALDES A M, WALTER J, SEGAL E, et al.Role of the gut microbiota in nutrition and health[J].BMJ (Clinical Research Ed.), 2018, 361:k2179.
[13] CANI P D.Microbiota and metabolites in metabolic diseases[J].Nature Reviews Endocrinology, 2019, 15(2):69-70.
[14] KO J H, KWON H S, YOON J M, et al.Effects of Polygonatum sibiricum rhizome ethanol extract in high-fat diet-fed mice[J].Pharmaceutical Biology, 2015, 53(4):563-570.
[15] 朱艳慧, 陈俭双, 文清, 等.高效液相色谱法同时测定金花清感颗粒中14种成分含量[J].中国医院药学杂志, 2021, 41(23):2 451-2 455.
ZHU Y H, CHEN J S, WEN Q, et al.Simultaneous determination of 14 components in Jinhua Qinggan Granules by high performance liquid chromatography[J].Chinese Journal of Hospital Pharmacy, 2021, 41(23):2 451-2 455.
[16] 杨兴鑫, 王曦, 董金材, 等.滇黄精对非酒精性脂肪肝大鼠的保护作用及机制研究[J].中国药学杂志, 2018, 53(12):975-981.
YANG X X, WANG X, DONG J C, et al.Protective effects and mechanisms of Polygonatum kingianum on nonalcoholic fatty liver in rats[J].Chinese Pharmaceutical Journal, 2018, 53(12):975-981.
[17] 马依依, 屈磊, 张帆, 等.脂蛋白肾病肾脏组织油红O染色方法改良[J].临床与实验病理学杂志, 2020, 36(9):1 114-1 115.
MA Y Y, QU L, ZHANG F, et al.Improved oil red O staining method for kidney tissues with lipoprotein nephropathy [J].Chinese Journal of Clinical and Experimental Pathology, 2020, 36(9):1 114-1 115.
[18] RUIZ-OJEDA F J, PLAZA-DÍAZ J, SÁEZ-LARA M J, et al.Effects of sweeteners on the gut microbiota:A review of experimental studies and clinical trials[J].Advances in Nutrition, 2019, 10(suppl_1):S31-S48.
[19] LIU G M, BEI J, LIANG L, et al.Stachyose improves inflammation through modulating gut microbiota of high-fat diet/streptozotocin-induced type 2 diabetes in rats[J].Molecular Nutrition & Food Research, 2018, 62(6):1700954.
[20] STRANDWITZ P,KIM K H,TEREKHOVA D, et al.GABA-modulating bacteria of the human gut microbiota[J].Nature Microbiology, 2019, 4(3):396-403.
[21] HWANG I, JO K, SHIN K C, et al.GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity[J].Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(24):11 936-11 945.
[22] PEDERSEN H K,GUDMUNDSDOTTIR V,NIELSEN H B, et al.Human gut microbes impact host serum metabolome and insulin sensitivity[J].Nature, 2016, 535(7 612):376-381.
[23] SONNER J K,KEIL M,FALK-PAULSEN M, et al.Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology[J].Nature Communications, 2019, 10(1):4877.
[24] SCOTT S A, FU J J, CHANG P V.Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor[J].Proceedings of the National Academy of Sciences of the United States of America, 2020, 117(32):19 376-19 387.
[25] AGUS A, PLANCHAIS J, SOKOL H.Gut microbiota regulation of tryptophan metabolism in health and disease[J].Cell Host & Microbe, 2018, 23(6):716-724.
[26] DU J J, ZHANG P W, LUO J, et al.Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family[J].Gut Microbes, 2021, 13(1):1862612.
[27] REIMER R A.Establishing the role of diet in the microbiota–disease axis[J].Nature Reviews Gastroenterology & Hepatology, 2019, 16(2):86-87.
[28] BLACHER E, LEVY M, TATIROVSKY E, et al.Microbiome-modulated metabolites at the interface of host immunity[J].Journal of Immunology, 2017, 198(2):572-580.
[29] TURNBAUGH P J,LEY R E,MAHOWALD M A, et al.An obesity-associated gut microbiome with increased capacity for energy harvest[J].Nature, 2006, 444(7 122):1 027-1 031.
[30] MAGNE F, GOTTELAND M, GAUTHIER L, et al.The firmicutes/bacteroidetes ratio:A relevant marker of gut dysbiosis in obese patients?[J].Nutrients, 2020, 12(5):1474.
[31] KONG C, GAO R Y, YAN X B, et al.Probiotics improve gut microbiota dysbiosis in obese mice fed a high-fat or high-sucrose diet[J].Nutrition, 2019, 60:175-184.
[32] OLIVER L, RAMIÓ-PUJOL S, AMOEDO J, et al.A novel grape-derived prebiotic selectively enhances abundance and metabolic activity of butyrate-producing bacteria in faecal samples[J].Frontiers in Microbiology, 2021, 12:639948.
[33] CHEN H T, ZHANG F, ZHANG J, et al.A holistic view of berberine inhibiting intestinal carcinogenesis in conventional mice based on microbiome-metabolomics analysis[J].Frontiers in Immunology, 2020, 11:588079.
[34] LIU Z,DAI X,ZHANG H, et al.Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment [J].Nature Communications, 2020, 11(1):855.
[35] RIZVI Z A, DALAL R, SADHU S, et al.High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity[J].Science Advances, 2021, 7(37):eabg5016.
[36] PUJO J, PETITFILS C, LE FAOUDER P, et al.Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis[J].Gut, 2021, 70(6):1 088-1 097.
[37] CEKANAVICIUTE E, YOO B B, RUNIA T F, et al.Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models[J].Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(40):10 713-10 718.
[38] ROM O, LIU Y H, LIU Z P, et al.Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome[J].Science Translational Medicine, 2020, 12(572):eaaz2841.
[39] HUART J,LEENDERS J,TAMINIAU B, et al.Gut microbiota and fecal levels of short-chain fatty acids differ upon 24-hour blood pressure levels in men [J].Hypertension, 2019, 74(4):1 005-1 013.
[40] THINGHOLM L B,RÜHLEMANN M C,KOCH M, et al.Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition [J].Cell Host Microbe, 2019, 26(2):252-264.
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