Wang Lili, Xin Yongning, Zhou Jianhua, Tian Zibin, Liu Chenguang, Yu Xinjuan, Meng Xinying, Jiang Weina, Zhao Shoufeng, Dong Quanjiang
Central Laboratories, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Front Microbiol. 2020 Jul 7;11:1548. doi: 10.3389/fmicb.2020.01548. eCollection 2020.
Alterations in the microbiome are associated with the development of gastric cancer. Our study aimed to identify dysbiotic features in early gastric cancer (EC). The gastric microbiome was assessed in EC ( = 30), advanced gastric cancer (AC) ( = 30), and chronic gastritis (CG) ( = 60). The results demonstrated significant differences in the microbial profile and composition between EC and AC, suggesting alterations associated with gastric cancer progression. Linear discriminant analysis (LDA) effect size (LEfSe) analyses identified 32 bacterial genera that were associated with EC. Functional analyses of the gastric microbiome showed that the production of urease and synthesis of bacterial flagella were weakened in EC, while the glycolysis of fructose and hydrolysis of glycosides were enhanced. A classifier based on a random forest (RF) machine learning algorithm identified a microbial signature that distinguished EC from CG or AC with high accuracy. The correct identification of the signature was further validated in independent cohorts. This signature enriched of bacteria with varied abundance, high degree of bacterial interactions and carcinogenic potentials. Constrained principal coordinate analyses revealed that the presence of and the and virulence genotypes influenced the structure of the gastric microbiome. To determine the impacts of host genetic variations on the gastric microbiome, six previously reported single nucleotide polymorphisms (SNPs) were examined. The minor allele of rs4072037 was associated with an increased abundance of . The gastric microbiome altered in EC, which might be attributed in part to host genetic variations, infection, bacterial virulence and environmental adaptations. The identified microbial signature could serve as biomarkers for clinical assessment of gastric cancer risk in high-risk patients.
微生物组的改变与胃癌的发生发展有关。我们的研究旨在确定早期胃癌（EC）中的生态失调特征。对EC（n = 30）、进展期胃癌（AC）（n = 30）和慢性胃炎（CG）（n = 60）的胃微生物组进行了评估。结果表明，EC和AC之间的微生物谱和组成存在显著差异，提示与胃癌进展相关的改变。线性判别分析（LDA）效应大小（LEfSe）分析确定了32个与EC相关的细菌属。胃微生物组的功能分析表明，EC中脲酶的产生和细菌鞭毛的合成减弱，而果糖的糖酵解和糖苷的水解增强。基于随机森林（RF）机器学习算法的分类器识别出一种微生物特征，可高精度地区分EC与CG或AC。在独立队列中进一步验证了该特征的正确识别。该特征富含丰度各异、细菌相互作用程度高且具有致癌潜力的细菌。受限主坐标分析表明，幽门螺杆菌的存在以及cagA和vacA毒力基因型影响了胃微生物组的结构。为了确定宿主基因变异对胃微生物组的影响，检查了6个先前报道的单核苷酸多态性（SNP）。rs4072037的次要等位基因与幽门螺杆菌丰度增加有关。EC中的胃微生物组发生了改变，这可能部分归因于宿主基因变异、幽门螺杆菌感染、细菌毒力和环境适应性。所识别的微生物特征可作为高危患者胃癌风险临床评估的生物标志物。
