代谢相关性脂肪性肝病小鼠不同高脂饮食时期血糖水平和肠道菌群变化动态分析*

doi:10.3969/j.issn.1672-5069.2021.05.014

实用肝脏病杂志 ›› 2021, Vol. 24 ›› Issue (5): 661-664.doi: 10.3969/j.issn.1672-5069.2021.05.014

代谢相关性脂肪性肝病小鼠不同高脂饮食时期血糖水平和肠道菌群变化动态分析^*

首第文, 周永健, 徐豪明, 唐文娟, 骆庆玲, 梅情, 宁钢, 赵冲, 黄红丽, 曹创裕, 陈慧婷

510006 广州市华南理工大学医学院(首第文,周永健,徐豪明,梅情);华南理工大学医学院附属第二医院消化内科(周永健,唐文娟,骆庆玲,宁钢,赵冲,黄红丽,曹创裕,陈慧婷)

收稿日期:2020-12-03 发布日期:2021-10-21
通讯作者: 周永健,E-mail: eyzhouyongjian@scut.edu.cn
作者简介:首第文,女,26岁,硕士研究生,住院医师。E-mail: 494390971@qq.com
基金资助:
^*国家自然科学基金资助课题(编号:81970507);广东省自然科学基金资助项目(编号:2020A1515010100/2018A030310672);广州市临床高新技术研究项目(编号:2019GX05);广州市科技计划项目(编号:201904010132);广州市卫生健康科技项目(编号:20191A011001);广东省医学科学技术研究基金资助项目(编号:A2020411)

Dynamic changes of blood glucose levels and gut microbiota in mice with high-fat diet-induced metabolic associated fatty liver diseases

Shou Diwen, Zhou Yongjian, Xu Haoming, et al

School of Medicine, South China University of Technology, Guangzhou 510006,Guangdong Province, China

Received:2020-12-03 Published:2021-10-21

摘要/Abstract

摘要： 目的探讨在不同高脂饮食喂养时期代谢相关性脂肪性肝病(MAFLD)小鼠血糖水平和肠道菌群的动态变化。方法采用高脂食物饲喂12只C57BL/6小鼠24周,分别在喂养0周、8周、16周和24周行葡萄糖耐量试验(GTT)和胰岛素耐受试验(ITT)。采集小鼠粪便进行16sRNA检测,分析肠道细菌结构和肠道菌群多样性的变化。结果随着高脂饮食喂养时间的延长,GTT和ITT试验显著血糖大幅度升高(P<0.05),肠道菌群阿尔法多样性chao1指数和ACE指数显著升高;在门水平,与0周比,喂养8周、16周和24周小鼠菌群厚壁菌门(Firmicutes)和变形菌门(Proteobacteria)比率显著升高(P<0.05),而拟杆菌门(Bacteroidetes)和疣微菌门(Verrucomicrobia)比率显著下降(P<0.05);在属水平,与0周比,高脂饮食喂养8周、16周和24周小鼠艾克曼菌(Akkermansia)和瘤胃球菌科-UCG-014属(Ruminococcaceae_UCG-014)比率显著降低(P<0.05),而红蝽杆菌科-UCG_002属(Coriobacteriaceae_UCG-002)比率显著升高(P<0.05),在喂养24周时杜氏杆菌(Dubosiella)比率显著升高(P<0.05),差异有统计学意义。结论随着高脂饮食喂养时间延长,小鼠血糖水平升高,肠道菌群阿尔法多样性持续增加,在门和属水平细菌结构发生了显著的改变。

关键词: 代谢相关性脂肪性肝病, 高脂饮食, 血糖, 肠道菌群, 小鼠

Abstract: Objective The purpose of this experiment was to investigate the dynamic changes of blood glucose levels and gut microbiota in mice with high-fat diet-induced metabolic associated fatty liver diseases (MAFLD). Methods Twelve C57BL/6 mice were fed with 60% fat-calorie high-fat diet for 24 weeks. AT 0 weeks, 8 weeks, 16 weeks and 24 weeks, the glucose tolerance test (GTT) and insulin resistance test (ITT) were performed to evaluate glucose metabolism and insulin sensitivity. The mice feces were collected for 16sRNA detection to analyze the changes of bacterial structure and diversity of gut microbiota. Results As the high-fat diet prolonged, the blood glucose by GTT and by ITT increased significantly (P <0.05); the chao1 index and ACE index increased, suggesting that the diversity of intestinal microflora increased as the high-fat diet continued; at the phylum levels, the percentages of Firmicutes and Proteobacteria at week 8, 16 and 24 were significantly increased compared with that at week 0 (P < 0.05), while the percentages of Bacteroidetes and Verrucomicrobia were significantly decreased (P <0.05); at the genus levels, the percentages of Akkermansia and Ruminococcaceae-UCG-014 were significantly decreased after high-fat diet at week 8, 16 and 24 (P<0.05), while percentage of Coriobacteriaceae-UCG_002 was significantly increased (P<0.05) compared with that at week 0; at week 24, the percentage of Dubosiella increased compared with that at week 0 (P<0.05). Conclusion With the prolongation of high-fat diet feeding, the blood glucose levels of mice gradually increase, the alpha diversity of the gut microbiota continues to increase, and the bacterial structure at the phylum and genus levels change, which warrants further investigation.

Key words: Metabolic associated fatty liver disease, High-fat diet, Blood glucose, Gut microbiota, Mice

首第文, 周永健, 徐豪明, 唐文娟, 骆庆玲, 梅情, 宁钢, 赵冲, 黄红丽, 曹创裕, 陈慧婷. 代谢相关性脂肪性肝病小鼠不同高脂饮食时期血糖水平和肠道菌群变化动态分析^*[J]. 实用肝脏病杂志, 2021, 24(5): 661-664.

Shou Diwen, Zhou Yongjian, Xu Haoming, et al. Dynamic changes of blood glucose levels and gut microbiota in mice with high-fat diet-induced metabolic associated fatty liver diseases[J]. Journal of Practical Hepatology, 2021, 24(5): 661-664.

参考文献

[1]Eslam M, Sanyal A J, George J, et al. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology, 2020,158(7):1999-2014.
[2]Mak L, Yuen M, Seto W. Letter regarding "A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement". J Hepatol, 2020,73(6):1573-1574.
[3]Vesa C M, Behl T, Nemeth S, et al. Prediction of NAFLD occurrence in prediabetes patients. Exp Ther Med, 2020,20(6):190.
[4]Alejandra P D O, Julián M T, Ramos A, et al. Microbiota, fiber, and NAFLD: is there any connection? Nutrients, 2020,12(10):3100.
[5]Jayakumar S, Loomba R. Review article: emerging role of the gut microbiome in the progression of non-alcoholic fatty liver disease and potential therapeutic implications. Aliment Pharmacol Ther, 2019,50(2):144-158.
[6]Jiao H, Lim A S, Fazio Coles T E, et al. The effect of high-fat diet-induced metabolic disturbance on corneal neuroimmune features. Exp Eye Res, 2020,201:108298.
[7]Lee H A, Cho J, Afinanisa Q, et al. Ganoderma lucidum extract reduces insulin resistance by enhancing AMPK activation in high-fat diet-induced obese mice. Nutrients, 2020,12(11):3338.
[8]White J R, Nagarajan N, Pop M. Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS Comput Biol, 2009,5(4): e1000352.
[9]Fraulob J C, Ogg-Diamantino R, Fernandes-Santos C, et al. A mouse model of metabolic syndrome: insulin resistance, fatty liver and non-alcoholic fatty pancreas disease (NAFPD) in C57BL/6 mice fed a high fat diet. J Clin Biochem Nutr, 2010,46(3):212-223.
[10] Schwimmer J B, Johnson J S, Angeles J E, et al. Microbiome signatures associated with steatohepatitis and moderate to severe fibrosis in children with non-alcoholic fatty liver disease. Gastroenterology, 2019,157(4):1109-1122.
[11] Ghoshal U C, Goel A, Quigley E M M. Gut microbiota abnormalities, small intestinal bacterial overgrowth, and non-alcoholic fatty liver disease: an emerging paradigm. Indian J Gastroenterol, 2020,39(1):9-21.
[12] Simoes I C M, Janikiewicz J, Bauer J, et al. Fat and sugar-a dangerous duet. A comparative review on metabolic remodeling in rodent models of non-alcoholic fatty liver disease. Nutrients, 2019,11(12):2871.
[13] Gastaldelli A. Insulin resistance and reduced metabolic flexibility: cause or consequence of NAFLD? Clin Sci, 2017,131(22):2701-2704.
[14] Turnbaugh P J, Ley R E, Mahowald M A, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 2006,444(7122):1027-1031.
[15] Kim S, Lee Y, Kim Y, et al. Akkermansia muciniphila prevents fatty liver disease, decreases serum triglycerides, and maintains gut homeostasis. Appl Environ Microbiol, 2020,86(7):e03004-30019.
[16] Zhang X, Shen D, Fang Z, et al. Human gut microbiota changes reveal the progression of glucose intolerance. PloS one, 2013,8(8):e71108.
[17] Naito Y, Uchiyama K, Takagi T. A next-generation beneficial microbe: Akkermansia muciniphila. J Clin Biochem Nutr, 2018,63(1):33-35.
[18] Shin N, Lee J, Lee H, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut, 2014,63(5):727-735.
[19] Wang P, Li D, Ke W, et al. Resveratrol-induced gut microbiota reduces obesity in high-fat diet-fed mice. Int J Obes, 2019,44(1):213-225.

代谢相关性脂肪性肝病小鼠不同高脂饮食时期血糖水平和肠道菌群变化动态分析^*

Dynamic changes of blood glucose levels and gut microbiota in mice with high-fat diet-induced metabolic associated fatty liver diseases

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