幽门螺杆菌（H. pylori）已被认为是胃癌（GC）明确的致癌细菌。这项多组学研究旨在调查胃癌患者感染幽门螺杆菌后的遗传、微生物和代谢变化。我们首先挖掘癌症基因组图谱胃癌 (STAD) 数据，以确定幽门螺杆菌阳性 GC 个体与幽门螺杆菌阴性 GC 个体相比的关键基因和关键通路。然后，从筛选合格的GC个体中采集新鲜粪便样本，并分析幽门螺杆菌阳性和幽门螺杆菌阴性GC个体之间的微生物变化和代谢物变化。最后，我们试图探索感染幽门螺杆菌的胃癌患者关键肠道菌群与代谢物变化之间的相互作用。我们确定了与幽门螺杆菌感染显着相关的三个基因（GCG、APOA1 和 IGFBP1），基于这三个幽门螺杆菌相关基因的生存会标对 GC 个体的总体生存表现出良好的预测能力。 16S rRNA测序显示，在幽门螺杆菌GC病例中，大肠杆菌、拟杆菌、肠球菌和乳杆菌的丰度在属水平上调。 H. pylori 群体与非 H. pylori 群体的 α 和 β 多样性存在较大差异。幽门螺杆菌组。非靶向代谢组分析确定了 295 种显着的粪便代谢物，并且幽门螺杆菌组中青霉烯 E、茄香醇、粪胆素原和赖氨酸 thr 的水平上调。最后，相关分析表明粪便代谢物与肠道菌株之间存在显着相关性。这是第一个通过多组学分析探讨携带幽门螺杆菌的GC患者与不携带幽门螺杆菌的GC患者之间差异的临床研究。 16S rRNA 测序以及非靶向代谢组学证明，幽门螺杆菌感染的胃癌个体中微生物多样性下降和代谢失调。 重要性这是第一项系统阐述幽门螺杆菌胃癌 (GC) 个体与未感染幽门螺杆菌的胃癌 (GC) 个体之间差异的临床研究. 多组学视角下的幽门螺杆菌。这项临床研究鉴定了重要的基因、微生物和粪便代谢物，在区分感染幽门螺杆菌的 GC 个体和未感染幽门螺杆菌的 GC 个体方面表现出良好的能力。这项研究为更好地了解 GC 人群的根除治疗提供了重要基础。

Helicobacter pylori (H. pylori) has been regarded as a definite carcinogenic bacterium for gastric cancer (GC). This multi-omics research was designed to investigate the genetic, microbial, and metabolic changes of GC patients when they are infected with H. pylori. We first mined The Cancer Genome Atlas Stomach Adenocarcinoma (STAD) data to identify the key genes and critical pathways in H. pylori-positive individuals with GC compared to H. pylori-negative individuals with GC. Then, fresh stool samples were collected from GC individuals screened for eligibility, and we analyzed the microbial changes and metabolite alterations between H. pylori-positive and H. pylori-negative GC individuals. Finally, we tried to explore the interaction between key gut flora and metabolite changes in GC patients infected with H. pylori. We identified three genes (GCG, APOA1, and IGFBP1) with significant relevance to H. pylori infection, and the survival monogram based on the three H. pylori-related genes showed good predictive ability for overall survival among GC individuals. 16S rRNA sequencing showed that the abundance of Escherichia-Shigella, Bacteroides, Enterococcus, and Lactobacillus was upregulated in GC cases with H. pylori at the level of genus. There exists a great difference in alpha and beta diversity between H. pylori group and non-H. pylori group. The untargeted metabolome analysis identified 295 significant fecal metabolites, and the levels of penitrem E, auberganol, stercobilinogen, and lys thr are upregulated in the H. pylori group. Finally, correlation analysis showed that there exists a significant correlation between the fecal metabolites and gut bacterial strains. This is the first clinical research to investigate the difference between GC patients with H. pylori and GC patients without H. pylori via multi-omics analysis. 16S rRNA sequencing along with untargeted metabolomics demonstrated decreased microbial diversity and metabolic dysregulation in gastric carcinoma individuals with H. pylori infection.IMPORTANCEThis is the first clinical research to systematically expound the difference between gastric cancer (GC) individuals with Helicobacter pylori and GC individuals without H. pylori from the perspective of multi-omics. This clinical study identified significant genes, microbes, and fecal metabolites, which exhibited nice power for differentiating GC individuals with H. pylori infection from GC individuals without H. pylori infection. This study provides a crucial basis for a better understanding of eradication therapy among the GC population.