非酒精性脂肪性肝病对肠道菌群多样性影响的初步研究

摘要/Abstract

摘要： 目的通过高脂饮食建立非酒精性脂肪性肝病(NAFLD)大鼠模型,观察NAFLD对肠道菌群多样性及群落组成的影响。方法建立NAFLD大鼠模型,通过大鼠肝脏病理切片HE染色验证NAFLD模型的成立,利用16sRNA测序技术对粪便肠道微生物进行检测分析,探讨NAFLD对肠道菌群多样性及群落组成的影响。结果肝脏组织学检查显示NAFLD组大鼠肝脏脂肪变明显,提示NAFLD动物模型建立成功。对照组Shannon多样性指数显著高于NAFLD组(P<0.05)。提示对照组的肠道微生物多样性显著丰富于NAFLD组。在门水平的变化情况提示,与对照组相比,NAFLD组中厚壁菌门和变形菌门的相对丰度较高(均P<0.05),而拟杆菌门的相对丰度则较低(P<0.05)。在科水平的变化情况提示,正常对照组以毛螺菌科、瘤胃球菌科、拟杆菌科_S24-7为优势菌科,而NAFLD组则以毛螺菌科、瘤胃球菌科为优势菌科。与对照组相比,NAFLD组中的毛螺菌科、拟杆菌科、脱硫弧菌科、氨基酸球菌科、Christensenellaceae菌科等相对含量较高(均P<0.05),而拟杆菌科_S24-7、普雷沃氏菌科、乳杆菌科等相对含量较低(均P<0.05)。结论 NAFLD可降低肠道菌群的多样性,并且显著改变肠道菌群的组成和含量。

关键词: 非酒精性脂肪性肝病, 肠道菌群, 多样性

Abstract: Objective To investigate the effect of nonalcoholic fatty liver disease (NAFLD) on the diversity of intestinal flora.Methods The NAFLD rat model was established by feeding high fat diet for 18 weeks and validated by liver histological examination. Fecal microbial flora was detected by 16sRNA sequencing technique. Results Liver histology showed bullae and microvesicular fatty degeneration and ballooning, which suggested NAFLD rat model was successfully constructed. Shannon index of control group was significantly higher than that of NAFLD group (P<0.05), suggesting that the microbial diversity in control group was significantly higher than that in NAFLD group. Changes at phylum level of intestinal flora revealed that the relative abundance of Firmicutes and Proteobacteria in NAFLD group were significantly higher (P<0.05) than that in control group, while the relative abundance of Bacteroidetes is significantly lower (P<0.05). Changes at family level of intestinal flora showed that the dominant bacteria were Lachnospiraceae, Ruminococcaceae and Bacteroidales_S24-7_group in control group, while Lachnospiraceae and Ruminococcaceae in NAFLD group. Compared with those in control group, the relative abundance of Lachnospiraceae, Bacteroidaceae, Desulfovibrionaceae, Acidaminococcaceae and Christensenellaceae were significantly higher (P<0.05) in NAFLD group, while the relative abundance of Bacteroidales_S24-7_group, Prevotellaceae and Lactobacillaceae were significantly lower (P<0.05). Conclusion NAFLD can impair the diversity of intestinal flora and significantly change the composition and content of intestinal flora.

Key words: Nonalcoholic fatty liver disease, Intestinal flora, Diversity

张静怡,唐颖悦,李春敏,明雅南,唐洁婷,曾民德,茅益民. 非酒精性脂肪性肝病对肠道菌群多样性影响的初步研究[J]. 肝脏, 2017, 22(4): 323-326.

ZHANG Jing-yi,TANG Ying-yue,LI Chun-min,MING Ya-nan,TANG Jie-ting,ZENG Min-de,MAO Yi-min. Effect of nonalcoholic fatty liver disease on diversity of intestinal flora[J]. Chinese Hepatolgy, 2017, 22(4): 323-326.

参考文献 19

[1]	Younossi ZM, Koenig AB, Abdelatif D, et al.Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.Hepatology, 2016, 64: 73-84.
[2]	Lazo M, Hernaez R, Bonekamp S, et al.Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ Open, 2011,343:d6891.
[3]	Tilg H, Cani PD, Mayer EA. Gut microbiome and liver diseases. Gut, 2016, 65: 2035-2044.
[4]	Hjelkrem MC, Torres DM, Harrison SA. Nonalcoholic fatty liver disease. Minerva Med, 2008, 99: 583-593.
[5]	陈一奕, 范竹萍, 茅益民, 等.非酒精性脂肪性肝病与代谢综合征的流行现状及相关性研究. 肝脏, 2008,13: 456-458.
[6]	范建高.中国非酒精性脂肪性肝病诊疗指南(2010年修订版). 中国医学前沿杂志, 2012: 4-10.
[7]	刘晓琳, 茅益民, 曾民德.非酒精性脂肪性肝病的组学研究进展与展望. 肝脏, 2013,18: 478-482.
[8]	Wree A, Schlattjan M, Bechmann LP, et al.Adipocyte cell size, free fatty acids and apolipoproteins are associated with non-alcoholic liver injury progression in severely obese patients. J Clin Endocr Metab, 2014, 63: 1542-1552.
[9]	Armstrong MJ, Adams LA, Canbay A, et al.Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology, 2014, 59: 1174-1197.
[10]	Fukuda S, Ohno H.Gut microbiome and metabolic diseases. Semin Immunopathol, 2014, 36: 103-114.
[11]	Li DY, Yang M, Edwards S, et al.Nonalcoholic Fatty Liver Disease: For Better or Worse, Blame the Gut Microbiota Jpen-parenter Enter, 2013,37: 787-793.
[12]	Moschen AR, Kaser S, Tilg H.Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrin Met, 2013, 24: 537-545.
[13]	Aron-Wisnewsky J, Gaborit B, Dutour A, et al.Gut microbiota and non-alcoholic fatty liver disease: new insights. Clin Microbiol Infec, 2013,19: 338-348.
[14]	Ramakrishna BS.Role of the gut microbiota in human nutrition and metabolism. J Gastroen Hepatol, 2013, 28: 9-17.
[15]	Yin X, Peng J, Zhao L, et al.Structural changes of gut microbiota in a rat non-alcoholic fatty liver disease model treated with a Chinese herbal formula. Syst Appl Microbiol, 2013,36: 188-196.
[16]	Goel A, Gupta M, Aggarwal R.Gut microbiota and liver disease. J Gastroen Hepatol, 2014, 29: 1139-1148.
[17]	Geurts L, Neyrinck AM, Delzenne NM, et al. Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics. Benef Microbes, 2014, 5: 3-17.
[18]	Turnbaugh PJ, Ley RE, Mahowald M A, et al.An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 2006, 444: 1027-1031.
[19]	Frasinariu OE, Ceccarelli S, Alisi A, et al.Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: An input for novel therapies. Digest Liver Dis, 2013, 45: 543-551.