非酒精性脂肪性肝病患者肠道菌群特点及肠道炎症研究

发布时间：2018-05-22 10:22

本文选题：非酒精性脂肪性肝病 + 肠道菌群失调　；参考：《南方医科大学》2017年硕士论文

【摘要】：研究背景非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是以肝脏过量脂肪浸润为病理特点的一种代谢性肝脏损伤,目前已成为最常见的慢性肝脏疾病。新近研究发现,肠道菌群失调与NAFLD的发生、发展相关。肠道菌群失调是导致肠道炎症的重要因素,而肠道炎症状态在NAFLD中的研究鲜见报道,肠道菌群失调与肠道炎症在NAFLD中的作用值得进一步探讨。目的明确NAFLD患者肠道菌群结构特点及肠道炎症状态。方法研究纳入2015年5月～2016年8月在南京军区南京总院门诊就诊的81例NAFLD患者,并选取同期本院体检中心91例体检者作为健康对照。收集入选对象的血清及粪便样品,分别进行血液生化学检测及粪便钙卫蛋白(fecal calprotectin,FC)检测(ELISA法)。此外,其中的24例NAFLD患者及18例对照者的粪便样品进行16SrRNA测序。两组间比较采用独立样本的T检验,计数资料采用X2检验。采用Spearman法进行相关性分析,采用Logistic回归进行多因素分析。统计分析采用SPSS 20.0软件进行分析,P0.05为差异有统计学意义。结果1.一般情况:NAFLD组的体质指数(BMI)、腰围、尿酸、血糖、AST、ALT、GGT、TC、TG及LDL的水平均明显高于健康对照组;NAFLD组HDL的水平低于健康对照组;多因素分析发现TG、TC、HDL及BMI是NAFLD发病的独立危险因子。2.肠道菌群组成分析:厚壁菌门、拟杆菌门、变形菌门以及放线菌门是两组研究对象肠道中的四大优势菌门,其占细菌总量的95%以上。在细菌门分类学水平上,拟杆菌门在NAFLD组中的丰度(30.46%)低于健康对照组(46.43%)(P0.05),变形菌门在NAFLD组的丰度(23.21%)高于健康对照组(7.99%)(P0.05),NAFLD患者粪菌中变形菌门/拟杆菌门比值较健康对照组显著升高(P0.01),厚壁菌门及放线菌门的丰度差异在两组间无统计学意义;在细菌科及属的分类学水平上,NAFLD组患者粪菌中拟杆菌科、拟杆菌属的丰度显著低于健康对照组(P0.01),大肠杆菌科及埃希氏菌属的丰度则显著高于健康对照组(P0.01),埃希菌属/拟杆菌属比值显著高于健康对照组(P0.01)。3.FC检测:NAFLD组的FC平均浓度(43.0(18.8-87.0)μg/g)高于正常对照组(11.4(4.6-24.4)μg/g)(P0.001)。FC水平与BMI、TC及GGT的水平均具有相关性,相关系数分别为0.725(P0.001)、0.292(P =0.010)及0.400(P0.01)。4.肠道菌群失调与FC相关性分析:FC浓度与埃希氏菌属的丰度呈正相关(r=0.644,P0.001),与拟杆菌属的丰度呈负相关(r=-0.426,P= 0.038),与埃希菌属/拟杆菌属丰度的比值呈显著正相关(r=0.810,P0.001)。结论NAFLD患者存在肠道炎症,以及以埃希氏菌属/拟杆菌属丰度比值升高为特征的菌群失调,二者之间存在良好的相关性。肠道菌群菌群失调及肠道炎症可能与NAFLD的发生发展相关。
[Abstract]:Background Non-alcoholic fatty liver disease (NAF LDD) is a metabolic liver injury characterized by excessive fatty infiltration of the liver. It has become the most common chronic liver disease. Recent studies have found that intestinal dysbacteriosis is associated with the occurrence and development of NAFLD. Intestinal dysbacteriosis is an important factor leading to intestinal inflammation, and the study of intestinal inflammatory status in NAFLD is rarely reported. The role of intestinal dysbacteriosis and intestinal inflammation in NAFLD should be further discussed. Objective to identify the intestinal flora and intestinal inflammation in patients with NAFLD. Methods from May 2015 to August 2016, 81 patients with NAFLD were enrolled in the outpatient clinic of Nanjing General Hospital of Nanjing military region, and 91 medical examiners in the same period were selected as healthy control. Serum and fecal samples were collected, blood biochemistry and fecal calcitonin were detected by Elisa. In addition, stool samples from 24 NAFLD patients and 18 controls were sequenced by 16SrRNA. The T test of independent samples and X 2 test were used to compare the data between the two groups. Correlation analysis was carried out by Spearman method and multivariate analysis by Logistic regression. Statistical analysis using SPSS 20.0 software to analyze the difference was statistically significant. Result 1. In general, the body mass index (BMI), waist circumference, uric acid, TG and LDL levels in the 10% NAFLD group were significantly higher than those in the healthy control group, and the multivariate analysis showed that TGP HDL and BMI were the independent risk factors of NAFLD. The composition of intestinal microflora: phylum, Bacteroides, Proteus and Actinomycetes were the four dominant phylum in the intestinal tract of the two groups, which accounted for more than 95% of the total number of bacteria. At the level of phylum taxonomy, The abundance of Bacteroides in NAFLD group (30.46) was lower than that in healthy control group (46.43) and the abundance of Proteus in NAFLD group (23.21) was higher than that in healthy control group (P 0.05%). The ratio of Proteus to Bacteroides in fecal bacteria in patients with NAFLD was significantly higher than that in healthy control group (P 0.01), and the ratio of Proteus to Bacteroides in healthy control group was significantly higher than that in healthy control group. There was no significant difference between the two groups in the abundance of actinomycetes and actinomycetes. Bacteroides in faecal bacteria of NAFLD group at the taxonomic level of the family Bacteriaceae and genera, The abundance of Bacteroides is significantly lower than that of the healthy control group (P 0.01), the abundance of Escherichia coli and Escherichia coli is significantly higher than that of the healthy control group (P 0.01), and the ratio of Escherichia coli to Bacteroides is significantly higher than that of the healthy control group. The average concentration of BMITC and GGT were significantly higher than those of normal control group (P < 0.05), the mean concentration of BMITC was 18.8-87.0 渭 g / g), and the level of BMITC and GGT was significantly higher than that of normal control group (11.4 渭 g/g)(P0.001).FC, 4.6-24.4 渭 g / g). The correlation coefficients were 0.725 (P 0.001), 0.292 (P) 0.010) and 0.400 (P 0.01) 路4, respectively. Analysis of correlation between intestinal flora imbalance and FC A positive correlation was found between the concentration of 10% FC and the abundance of Escherichia spp. 0.644m P0.001C, negatively correlated with the abundance of Bacteroides, r = 0.426 (P = 0.038), and with the ratio of the abundance of Escherichia / Bacteroides (R0.810P0.001). Conclusion there are intestinal inflammation in patients with NAFLD and the imbalance of flora characterized by the increase of the abundance ratio of Escherichia coli to Bacteroides, and there is a good correlation between them. Intestinal flora imbalance and intestinal inflammation may be related to the occurrence and development of NAFLD.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575

【参考文献】