Non-Helicobacter pylori Gastric Microbiome Modulates Prooncogenic Responses and Is Associated With Gastric Cancer Risk
Ryota Niikura, Yoku Hayakawa, Naoyoshi Nagata, Tohru Miyoshi-Akiayama, Koji Miyabayashi, Mayo Tsuboi, Nobumi Suzuki, Masahiro Hata, Junya Arai, Ken Kurokawa, Sohei Abe, Chie Uekura, Kotaro Miyoshi, Sozaburo Ihara, Yoshihiro Hirata, Atsuo Yamada, Hiroaki Fujiwara, Tetsuo Ushiku, Susan L. Woods, Daniel L. Worthley, Masanori Hatakeyama, Yiping W. Han, Timothy C. Wang, Takashi Kawai, Mitsuhiro Fujishiro
Abstract
Background and Aims: eradication. Studies suggest that various constituents of the gastric microbiome may influence GC development, but the role of individual pathogens is unclear. Methods: Human gastric mucosal samples were analyzed by 16SrRNA sequencing to investigate microbiome composition and its association with clinical parameters, including GC risk. Identified bacteria in the stomach were cocultured with gastric epithelial cells or inoculated into mice, and transcriptomic changes, DNA damage, and inflammation were analyzed. Bacterial reads in GC tissues were examined together with transcriptomic and genetic sequencing data in the cancer genome atlas dataset. Results: species were genotoxic, and the presence of the bacteria was associated with an inflammatory signature and a higher tumor mutation burden. Conclusion: eradication and plays a pathogenic role through direct host-bacteria interaction.