Tumor-Associated Microbiota in Esophageal Squamous Cell Carcinoma

Abstract

Background: Important evidence indicates that the intestinal tract microbiota plays a key role in esophageal squamous cell carcinoma (ESCC). Our objective is to analyze the composition of the ESCC-associated microbiota and characterize its contribution to the development of ESCC. Methods: The esophageal microbiota was prospectively investigated in 18 patients with ESCC and 11 patients with physiological normal (PN) esophagus by 16S rRNA gene profiling, using next-generation sequencing. The linear discriminant analysis effect size was used to assess the differences in microbial composition of PN esophagus and ESCC. Predictive functional profiling of microbial communities were obtained with PICRUSt. Findings: The microbiota composition in tumor tissues of ESCC patients is significantly different from that of patients with PN tissues. The ESCC microbiota was characterized by reduced microbial diversity, by decreased abundance of Bacteroidetes, Fusobacteria and Spirochactes. Employing these taxa into a microbial dysbiosis index demonstrated that dysbiosis microbiota had good capacity to discriminate between ESCC and PN esophagus. Functional analysis of the microbiota characterized that ESCC microbiota had altered nitrate reductase and nitrite reductase functions when compared with PN group. The observations were confirmed in other validation cohorts. Interpretation: Detailed analysis of the microbiota of the ESCC patients revealed that tumor exhibit a dysbiotic microbial community when compared with PN groups. We characterized microbial compositional changes, and further identified significant enrichments of Treponema amylovorum, Streptococcus infantis, Prevotella nigrescens, Porphyromonas endodontalis, Veillonella dispar, Aggregatibacter segnis, Prevotella melaninogenica, Prevotella intermedia, Prevotella tannerae, Prevotella nanceiensis and Streptococcus anginosus in ESCC oncogenic progression. Trial Registration: This GASTO1039 study was registered at http://www.chictr.org.cn/ (the Chinese Clinical Trial Registry: ChiCTR1800018897). Funding Statement: This research was supported by National Key R&D Program of China (2018YFC0910303), the National Natural Science Foundation of China (81572391, 81630072), Shenzhen Municipal Government (KQTD20170810160226082), Guangdong Basic and Applied Basic Research Foundation (2019A1515011874), and Guangzhou Municipal Science and Technology Bureau/Science and Technology program of Guangzhou city (201904010356). Declaration of Interests: Lu Gao is the employee of BGI Genomics, BGI-Shenzhen, China. The remaining authors declare no competing interests. Ethics Approval Statement: This prospective observational study was conducted according to a protocol approved by the respective Institutional Ethics Committees of the First Affiliated Hospital of Sun Yat-sen University and according to the Declaration of Helsinki.