基于高通量测序技术研究原发性胃癌患者胃肠道菌群特征  

Study on the characteristics of gastrointestinal flora in patients with primary gastric cancer based on high-throughput sequencing technology

作　　者：凌宝殿 谢志军[2] 张文娟 王晓玲 王芳胜 胡晓梅[1] 赖姨梅 吴何莉 胡龙华[4] LING Bao-dian;XIE Zhi-jun;ZHANG Wen-juan;WANG Xiao-ling;WANG Fang-sheng;HU Xiao-mei;LAI Yi-mei;WU He-li;HU Long-hua(Department of Clinical Laboratory,The First Affiliated Hospital of Gannan Medical University;Department of Gastroenterology,The First Affiliated Hospital of Gannan Medical University;Department of Pathology,The First Affiliated Hospital of Gannan Medical University,Ganzhou,Jiangxi 341000;Department of Clinical Laboratory,The Second Affiliated Hospital of Nanchang University Medical College,Nanchang,Jiangxi 330000)

机构地区：[1]赣南医学院第一附属医院检验科 [2]赣南医学院第一附属医院消化内科 [3]赣南医学院第一附属医院病理科,江西赣州341000 [4]南昌大学医学院第二附属医院检验科,江西南昌330000

出　　处：《赣南医学院学报》2023年第3期228-234,共7页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：江西省卫生计划生育委员会科技计划项目(20195406)。

摘　　要：目的:探讨原发性胃癌患者胃肠道菌群种类和分布构成,探究原发性胃癌患者的微生态与癌变发生相关性,并寻找可能存在的菌群生物标志物。方法:根据纳入排除标准,分别收集未经治疗的5例初诊胃癌患者(胃癌组)和5例健康对照人群(对照组)胃黏膜和粪便样本,共20个样本,采用16S rDNA基因高通量测序技术检测胃癌组和对照组胃肠道菌群,通过PICRUSt2预测菌群功能差异。结果:操作分类单元(Operational taxonomic units OTU)物种多样性分析显示,胃癌组和对照组胃黏膜样本优化序列数量差异无统计学意义,但胃癌组粪便(WAFB)OTU数明显高于对照组。两组间ɑ多样性指数Dominance、Shannon、Chao1、Simpson、Pielou_e及Observed_otus比较差异均无统计学意义,但距离矩阵与(主坐标分析)PCoA分析显示两组菌群结构存在显著差异。线性判别效应分析(LefSe)结果显示,在细菌分类的门水平上,与对照组相比,胃癌组黏膜(WANM)古细菌和拟杆菌门丰度降低,而厚壁菌门和弯曲杆菌门丰度增加,胃癌组粪便(WAFB)的厚壁菌门和放线菌门丰度降低,而变形杆菌门、拟杆菌门和弯曲杆菌门丰度增加。在属水平上,胃癌组大肠埃希菌-志贺菌属(Escherichia-Shigella)丰度高于对照组,而拟杆菌属(Bacteroides)等益生菌则低于对照组。功能基因预测结果显示,胃癌组与对照组菌群代谢通路存在差异。结论:胃癌患者胃肠道菌群多样性和结构发生了特征性改变,其中在门水平上,无论是胃黏膜菌群,还是肠道菌群,其拟杆菌门和变形杆菌门为具有显著差异的标志性菌群,在属水平上,胃癌患者大肠埃希菌-志贺菌属(Escherichia-Shigella)丰度显著增高,而拟杆菌属(Bacteroides)等益生菌则显著降低。大肠埃希菌-志贺菌属(Escherichia-Shigella)可能作为本地区胃癌患者潜在的生物标志物。Objective:To explore the types and distribution composition of gastrointestinal flora in patients with primary gastric cancer,clarify the synergistic rule of gastrointestinal flora,explore the microecological carcinogenic mechanism in patients with primary gastric cancer,and search for potential biomarkers of bacterial flora.Methods:According to the inclusion and exclusion criteria,Gastric mucosa and fecal samples were collected from 5 newly diagnosed gastric cancer patients and 5 healthy control cases without prior treatment,with a total of 20 samples,16S rDNA gene high-throughput sequencing technology was used to analyze the gastrointestinal flora,and PICRUSt2 predicted the functional differences of the flora.Results:Operational taxonomic units(OTU)analysis showed that there was no statistical difference in the number of optimized sequences of gastric mucosa samples between gastric cancer patients and normal control group,but the number of OTU in gastric cancer feces(WAFB)group was significantly higher than that in control group,indicating that the species richness of intestinal flora in gastric cancer group was greater than that in control group.The comparison of Alpha diversity index between the two groups,Shannon,Chao1,Simpson,Pielou_e and Observed_otus showed no statistical significance,but the distance matrix and PCoA analysis showed significant differences in microflora structure between the two groups.Linear discriminant effect analysis(LefSe)results showed that,at the phylum level of bacterial classification,the abundance of archaea and bacteroidetes decreased in gastric carcinoma mucosa(WANM)group,while the abundance of firmicutes and campylobacter increased;the abundance of firmicutes and actinomycetes decreased in gastric carcinoma feces(WAFB)group,while the abundance of proteobacteria,bacteroidetes and campylobacter increased.At the genus level,the abundance of Escherichia-Shigella in gastric cancer patients was significantly higher than that in the control group,while the abundance of Bacteroides a

关 键 词：胃黏膜菌群 肠道菌群 胃癌 16SrDNA 

分 类 号：R735.2[医药卫生—肿瘤]