533 Impact of Local Microbiome on the Onset of Esophageal Adenocarcinoma for the Development of a Strategy for Prevention and Treatment

Abstract

Esophageal adenocarcinoma (EAC) is one of the most aggressive gastrointestinal tumor. High mortality is due to difficulties in diagnosis at an early stage and to its biological aggressive features. Little is know about the association between esophageal microbiome dysbiosis and EAC pathogenesis. The aim of the study is the identification of a specific esophageal local microbiota that can be related to the pathogenesis and to the onset of EAC Methods We investigated the resident microbiome in 38 biopsies from Tumoral (T) and Non-Tumoral (NT) tissues obtained from 19 patients submitted to distal-EAC, cardiac-EAC, ESCC resection in Upper GI Surgery Division, Humanitas Research Hospital (Rozzano, Milano). We have analyzed the microbiota in biopsies obtained from EAC Tumoral tissues (T) and Non-Tumoral tissues (NT). After genomic DNA extraction the V3V4-hypervariable regions of the 16S-rRNA bacterial gene were amplified and sequenced on MiSeq Illumina sequencer. The Bioinformatic Data Analysis has been perfomed using the CLC Genomic Workbench. Results Alpha diversity analysis showed an increased microbial species richness in Esophageal Squamo-Cellular Carcinoma (ESCC) respect to distal/cardiac EAC and tissues without metaplasia. PERMANOVA statistical analysis was applied to estimate Beta Diversity significance. Bray-Curtis index showed a statistically significant different microbiome composition when comparing both cardiac and distal EAC versus ESCC (p-value 0.022 and 0.010 respectively) and when comparing samples with and without metaplasia. Relative abundances analysis obtained after the comparison of distal EAC, cardiac EAC and ESCC identified specific bacterial species in each group. Streptococcus genus is present only in cardiac EAC, Helicobacter pylori only in distal EAC. Conclusion Our study evidenced an increased microbial species richness in samples deriving from ESCC compared to EAC and samples without metaplasia. A significant difference was found comparing EAC with ESCC or with/without metaplasia tissues, mirroring a reduced biodiversity in EAC and metaplasia. We speculated a generalized alteration of the local microbiome from healthy to diseased tissue, characterized by certain bacterial strains that developed through the creation of a chronic inflammatory milieu that triggers the carcinogenic cascade.