Table_7_Changes of the Gastric Mucosal Microbiome Associated With Histological Stages of Gastric Carcinogenesis.xlsx

The changes of gastric microbiome across stages of neoplastic progression remain poorly understood, especially for intraepithelial neoplasia (IN) which has been recognized as a phenotypic bridge between atrophic/intestinal metaplastic lesions and invasive cancer. The gastric microbiota was investigated in 30 healthy controls (HC), 21 non-atrophic chronic gastritis (CG), 27 gastric intestinal metaplasia (IM), 25 IN, and 29 gastric cancer (GC) patients by 16S rRNA gene profiling. The bacterial diversity, and abundances of phyla Armatimonadetes, Chloroflexi, Elusimicrobia, Nitrospirae, Planctomycetes, Verrucomicrobia, and WS3 reduced progressively from CG, through IM, IN to GC. Actinobacteria, Bacteriodes, Firmicutes, Fusobacteria, SR1, and TM7 were enriched in the IN and GC. At the community level, the proportions of Gram-positive and anaerobic bacteria increased in the IN and GC compared to other histological types, whereas the aerobic and facultatively anaerobic bacteria taxa were significantly reduced in GC. Remarkable changes in the gastric microbiota functions were detected after the formation of IN. The reduced nitrite-oxidizing phylum Nitrospirae together with a decreased nitrate/nitrite reductase functions indicated nitrate accumulation during neoplastic progression. We constructed a random forest model, which had a very high accuracy (AUC > 0.95) in predicating the histological types with as low as five gastric bacterial taxa. In summary, the changing patterns of the gastric microbiota composition and function are highly indicative of stages of neoplastic progression.

胃微生物组随肿瘤进展各阶段的变化特征目前仍不甚明确，尤其是上皮内瘤变（intraepithelial neoplasia, IN）——其被认为是萎缩性/肠化生病变与浸润性癌症之间的表型过渡桥梁。本研究通过16S rRNA基因谱分析，对30例健康对照（healthy controls, HC）、21例非萎缩性慢性胃炎（non-atrophic chronic gastritis, CG）患者、27例胃肠化生（gastric intestinal metaplasia, IM）患者、25例上皮内瘤变患者及29例胃癌（gastric cancer, GC）患者的胃微生物组进行了研究。细菌多样性以及装甲菌门（Armatimonadetes）、绿弯菌门（Chloroflexi）、迷踪菌门（Elusimicrobia）、硝化螺旋菌门（Nitrospirae）、浮霉菌门（Planctomycetes）、疣微菌门（Verrucomicrobia）及WS3候选门的相对丰度，均从非萎缩性慢性胃炎、经肠化生、上皮内瘤变直至胃癌呈渐进性下降。放线菌门、拟杆菌门、厚壁菌门、梭杆菌门、SR1及TM7在上皮内瘤变及胃癌患者中均呈富集状态。在群落水平上，与其他组织学类型相比，上皮内瘤变及胃癌患者的革兰氏阳性菌与厌氧菌占比均有所上升；而胃癌患者中需氧菌及兼性厌氧菌类群的占比则显著下降。上皮内瘤变形成后，胃微生物组的功能发生了显著改变。具有亚硝酸盐氧化功能的硝化螺旋菌门丰度下降，加之硝酸盐/亚硝酸盐还原酶功能减弱，提示肿瘤进展过程中硝酸盐发生蓄积。本研究构建了随机森林模型，仅需5个胃细菌类群即可实现高精度的组织学类型预测，其曲线下面积（Area Under Curve, AUC）大于0.95。综上，胃微生物组组成与功能的变化模式可高度指示肿瘤进展的各阶段。