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Integrated analysis of mucosa-associated microbiome and host genotoxic changes in Barrett's esophagus and esophageal adenocarcinoma sequence
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Takuya Shijimaya1,
Tomomitsu Tahara1,
Makoto Naganuma1 |
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1Third Department of Internal Medicine, Kansai Medical University |
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| Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM and host genotoxic changes in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) sequence. 16S rRNA gene sequencing was performed in three different groups of biopsies from non-neoplastic BE from patients without cancer (n=47; N group), with EAC (n=27; ADJ group) and EAC tissue (n=22; T group). Results were correlated with DNA methylation status, TP53 mutation and telomere length. Lower microbial alpha diversity measures were observed in ADJ/T groups relative to N group and associated with higher mean Z score DNA methylation of candidate genes (N33, DPYS, SLC16A12, miR124A3 and miR34bc). Specific genera (n=16) with significant change between ADJ/T groups relative to N group occurred mostly in ADJ group (13/16) and half of them (8/16) were associated with DNA methylation status. Integrated MAM and genome-wide methylation analysis demonstrated that hyper-methylated sites, associated with lower alpha diversity measures dominantly occurred within near the TSS, codifying genes involved in metabolic processes. We concluded that microbial dysbiosis in EAC mostly occur in adjacent BE and such dysbiosis is associated with host genotoxic changes such as DNA methylation, offering support for a pathogenic role of interaction between host genotoxic changes and MAM in this tumor type. |
Index Term 1: Barrett's esophagus
Index Term 2: microbiome
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