摘要：SummaryTo date, there has been no multi-omic analysis characterizing the intricate relationships between the intragastric microbiome and gastric mucosal gene expression in gastric carcinogenesis. Using multi-omic approaches, we provide a comprehensive view of the connections between the microbiome and host gene expression in distinct stages of gastric carcinogenesis (i.e., healthy, gastritis, cancer). Our integrative analysis uncovers various associations specific to disease states. For example, uniquely in gastritis, Helicobacteraceae is highly correlated with the expression ofFAM3D, which has been previously implicated in gastrointestinal inflammation. In addition, in gastric cancer but not in adjacent gastritis, Lachnospiraceae is highly correlated with the expression ofUBD, which regulates mitosis and cell cycle time. Furthermore, lower abundances of B cell signatures in gastric cancer compared to gastritis may suggest a previously unidentified immune evasion process in gastric carcinogenesis. Our study provides the most comprehensive description of microbial, host transcriptomic, and immune cell factors of the gastric carcinogenesis pathway.Graphical abstractDisplay OmittedHighlights•Multi-omics finds genetic, microbial, and immunological links in gastric cancer•Helicobacteraceae was highly associated with the expression of inflammation genes•Pasteurellaceae and Lachnospiraceae were associated with cancer-related genes•B cell infiltration was prominent in gastritis tissues but not in gastric cancerCellular physiology; Microbiome; Omics
