Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer
Lei Lei,
Lin-Yong Zhao,
Ran Cheng,
Hongyu Zhang,
Mengying Xia,
Xiao-Long Chen,
Valentin Kudriashov,
Kai Liu,
Wei-Han Zhang,
Han Jiang,
Yi Chen,
Liang Zhu,
Hongmei Zhou,
Kun Yang,
Tao Hu,
Jian-Kun Hu
Affiliations
Lei Lei
State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Lin-Yong Zhao
Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
Ran Cheng
State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Hongyu Zhang
State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Mengying Xia
State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Xiao-Long Chen
Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
Valentin Kudriashov
Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
Kai Liu
Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
Wei-Han Zhang
Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
Han Jiang
State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Yi Chen
Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
Liang Zhu
Nuffield Department of Medicine, University of Oxford, Target Discovery Institute, Center for Medicines Discovery, Oxford, United Kingdom
Hongmei Zhou
State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Kun Yang
Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
Tao Hu
State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Jian-Kun Hu
Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
ABSTRACT The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs.IMPORTANCEOur study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.
