Microbial and Metabolomic Variations Correlated With Gastric Cancer Subtypes and Prognosis

Gastric cancer (GC) persists as the third most prevalent malignancy in China. GC exhibits distinct features when stratified by Lauren/ZJU subtypes. The interdependence of microbes, metabolites, and tumor evolution is recognized. Nevertheless, the specific microbial and metabolite disparities related to the Lauren and ZJU subtypes of GC have yet to be thoroughly investigated. In this study, we employed 16S sequencing of microbial communities and conducted untargeted metabolomic assessments on tumor tissues and their matched normal controls from 50 GC patients. We observed variations in microbial composition and metabolite landscapes across subtypes, irrespective of the Lauren or ZJU classification. We explored the associations and differences between the Lauren and the ZJU classification. It was found that both classifications share differential microbiota, including Fusobacterium and Haemophilus. Additionally, 38 of the top 50 differential metabolites are common to both classifications. However, distinct classifications also exhibit unique differential microbiota and metabolite characteristics. Among them, Eubacterium_ventriosum_group and N6-Succinyl Adenosine are both characteristic differences of the ZJU classification. Multivariate survival analysis disclosed that Eubacterium_ventriosum_group positively correlates with poor prognosis, whereas N6-Succinyl Adenosine negatively correlates with poor prognosis. Our research delineates the microbiota and metabolites specific to different subtypes of GC and investigates the interplay between these differential elements, as well as their prognostic significance. We have identified two distinct features that are both associated with the ZJU classification, suggesting that the ZJU classification is more closely related to prognosis.