结直肠腺瘤与息肉患者肠道菌群变化的病例对照研究  

Changes in gut microbiota of patients with colorectal adenoma and polyps:a case control study

作　　者：于鑫 张永镇 于恩达 王娜 帅群 闫飞虎 蒋露芳 王和兴[5] 刘健翔 陈跃[4] 李兆申 蔡全才 姜庆五 YU Xin;ZHANG Yong-zhen;YU Enda;WANG Na;SHUAI Qun;YAN Fei hu;JIANG Lu fang;WANG He xing;LIU Jian xiang;CHEN Yue;LI Zhao shen;CAI Quan cai;JIANG Qing wu(Key Laboratory of Public Health Safety ,Ministry of Education-Department of Epiderniology ,S Key Laboratory of Public Health Safety, Ministry of Education-Department of Nutrition and Food Hygine , Schoog of Public Health , Fudan University, Shanghai 200032, China;Department of Gastroenterology, 6 Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, China;Department of Gastroenterology, the 92914th Military Hospital of PLA ,Lingao 571833, Hainan Province, China;School of Epiderniology and Public Health, Faculty of Medicine, University of Ottawa , Ottawa K 10 5Z3, Canada)

机构地区：[1]复旦大学公共卫生学院流行病学教研室-教育部公共卫生安全重点实验室,上海200033 [2]海军军医大学附属长海医院消化内科,上海200433 [3]中国人民解放军92914部队医院消化内科,临高571833 [4]渥太华大学医学系流行病与公共卫生学院,渥太华KIG523 [5]复旦大学营养与食品卫生教研室-教育部公共卫生安全重点实验室,上海200032 [6]海军军医大学附属长海医院普外科,上海200433

出　　处：《复旦学报（医学版）》2018年第5期658-663,共6页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金(81473045,81273154)

摘　　要：目的分析结直肠癌早期阶段进展期腺瘤、单纯腺瘤和增生性息肉患者体内肠道菌群的变化。方法基于病例对照研究设计,研究对象来自2014—2015年长海医院门诊的肠镜受检者。共纳入进展期腺瘤患者88例、单纯腺瘤患者32例与增生性息肉患者30例(二者均为良性病变)以及130位无结直肠疾病的肠镜受检者(对照组)。收集肠镜检查前研究对象的粪便样本,对细菌16S rDNA中V3～V4区进行高通量测序,得到粪便样本的细菌组成,在此基础上进行生态学分析和细菌相对丰富度比较分析。结果进展期腺瘤、良性病变患者和对照组肠道菌群构成存在显著差异(P=0.005),而α多样性无显著差异。在进展期腺瘤患者粪便中发现牙周病相关细菌卟啉单胞菌属(Porphyromonas)和牙龈卟啉单胞菌(Porphyromonas gingivalis)显著上升(P值均小于0.001);益生菌双歧杆菌属(Bifidobacterium)(P=0.018)、丁酸梭菌(Clostridium butyricum)(P=0.001)和Streptococcus dentisani (P=0.028)丰富度显著降低。在良性病变组中观察到益生菌乳酸杆菌属(Lactobacillus)(P=0.044)和双歧杆菌属(Bifidobacterium)(P=0.001)的上升,丁酸梭菌下降(P=0.007)。结论进展期腺瘤、单纯腺瘤和增生性息肉患者的肠道菌群整体构成发生显著变化。进展期腺瘤患者体内牙周病致病菌丰富度上升、益生菌丰富度下降;良性病变患者某些益生菌丰富度发生变化。肠道菌群可能在结直肠癌早期阶段发挥作用。Objective To analyze the changes of gut microbiota in patients with precursor lesions of colorectal cancer including advanced colorectal adenocarcinomas （A CRA）, colorectal adenomas and hyperplastic polyps. Methods We conducted a case control study. The participants were from outpatients performed coloscopy during 2014 to 2015 in Changhai Hospital. Eighty eight initially diagnosed patients with A CRA,32 patients with colorectal adenoma, 30 patients with hyperplastic polyps and 130 controls without any colorectal diseases were included. Patients with colorectal adenomas and hyperplastic polyps were combined into the benign group. Stool specimen of all participants were collected before colonoscopy and V3 V4 region of bacterial 16S rDNA genes in the stool were sequenced to determine the taxa and composition of gut microbiota. Ecological and statistical analyses were applied based on the bacterial composition. Results Significant structural change was observed （P=0. 005） among patients with A CRA, benign lesions and controls,but no difference in diversity indices. Porphyromonas and Porphyromonas gingivalis, as pathogen for periodontal diseases, showed significantly high in the stool from A CRA patients （P〈0. 001 for both）. We also found BifidoSacteriurn （P=0. 018） ,Clostridium butyricum （P=0. 001） and Streptococcus dentisani （P=0. 028） were significantly depleted in the A CRA group. The abundance of LactoSacillus （P O. 044） and Bi fidoSacterium （P=0. 001） were increased, while Clotridiurn butyricum （ P=0.007） were decreased in the benign group. Conclusions Structural alternations were observed in gut microbiota of patients with A CRA, colorectal adenomas and hyperplastic polyps. The periodontal pathogens increased and several kinds of probiotics decreased in the A CRA patients. The abundance of probiotics changed in the polyps group. Microbiota may take part in the early stage of colorectal cancer.

关 键 词：进展期结直肠腺瘤 结直肠癌癌前病变 肠道菌群 高通量测序 

分 类 号：R735.3[医药卫生—肿瘤]