Abstract B09: Unravelling the gastric microbiome in health and disease: Gastric cancer beyond Helicobacter pylori in a Brazilian cohort

Abstract

Abstract Although numerous studies have shown the relevance of the gut microbiome in several diseases, underlying questions remain concerning the stomach microbiome and the establishment of a causal link between the microbiota and the development of gastric diseases, much beyond Helicobacter pylori and Epstein Barr virus. In this study, we aimed to characterize the bacterial composition of the stomach of subjects undergoing upper endoscopy, including gastric cancer (GC) individuals, aiming to identify fluctuations in bacterial populations that might be associated with stomach health. During endoscopic examination at A.C. Camargo Cancer Center (Sao Paulo, Brazil), gastric fluids (GF) were recovered from either GC patients (113) or individuals with gastric-related complaints, such as superficial gastritis (SG; 79), atrophic gastritis (AG; 12), and intestinal metaplasia (IM; 33). For eubacteria identification, the V3-V4 region of the 16S rRNA gene was amplified and paired-end sequenced (Illumina MiSeq). Analyses were carried out using Qiime2 and phyloseq packages. On average, we identified between 14 and 104 OTUs per subject, evidencing the potential of GFs for determining the stomach microbial composition and the interindividual variation. Testing of sample richness between GC and controls showed significant differences between the number of OTUs observed in each group (an average of 44 and 52 OTUs, respectively—Mann-Whitney test, p<0.05) and SG patients had a significantly increased alpha diversity (Shannon, p<0.05) as compared to AG, IM, and GC patients (both intestinal and diffuse subtypes), indicating dysbiosis already in early carcinogenesis steps. Additionally, the prolonged use of proton pump inhibitors or the presence of H. pylori (except for SG) did not seem to interfere with bacterial diversity. Specific genera are enriched in the sample subsets, including a lower presence of Corynebacterium and increased Streptococcus (Linear discriminant analysis Effect Size, LDA score >2) in AG samples as compared to SG patients, which are also increased in the IM, and GC. These results indicate these bacteria to be potentially associated with the stomach dysbiosis that may lead to the carcinogenesis cascade. Besides the regular turnover of the gastric epithelial tissue and pouring of cells onto the gastric cavity, GF certainly contains a high proportion of transient oral-derived bacteria, while stomach-resident microbiota is expected to be in close contact with the gastric epithelia. Preliminary data analyzing the bacterial content of the saliva x GF in a subset of patients showed no significant beta-diversity differences, but both fluids differ significantly from their biopsies’ composition. We are currently performing culturomics and transcriptomics to identify bacteria that are alive in the stomach. As GC is a complex malignancy with limited treatment options, these results may contribute to developing new interventions to treat and to better understand this disease. Citation Format: Thais F. Bartelli, Gabriela E. Albuquerque, Alexandre Defelicibus, Marianna S. Serpa, Lais L.S. Abrantes, Rodrigo Borges, Felipe Coimbra, Adriane G. Pelosof, Israel T. Silva, Diana N. Nunes, Emmanuel Dias-Neto. Unravelling the gastric microbiome in health and disease: Gastric cancer beyond Helicobacter pylori in a Brazilian cohort [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B09.