Dietary nitrate drives gastritis by modulating gastric microbiota and metabolites

OBJECTIVE: Dietary nitrate has been increasingly recognized as a potential carcinogen associated with gastritis. In this study the mechanistic role of a high-nitrate diet (NaD) in driving gastritis was elucidated with a focus on modulation of the gastric microbiota composition and metabolomic profiles. METHODS: Animals were randomly assigned to two dietary intervention groups using a C57BL/6 mouse model: a NaD containing 7.5% nitrate; or a standard normal diet (ND). Gastric microbiota composition was characterized based on full-length 16S rRNA sequencing and gastric metabolite profiles were analyzed using high-performance liquid chromatography-mass spectrometry (HPLC/MS). Finally, the roles of the microbiome and metabolites in gastritis development were validated using the human gastric epithelial cell line (GES-1), as well as conventional and germ-free mouse models. RESULTS: colonization and 5-HIAA exposure significantly increased inflammatory responses in conventional and germ-free mouse models. CONCLUSIONS: NaD drives gastritis in mice by inducing gastric microbial dysbiosis and metabolomic dysregulation with elevated 5-HIAA.