@article{Jiang2026, 
author = {Lanping Jiang and Tianhui Li and Jiayu Wu and Harry Cheuk Hay Lau and Chi Chun Wong and Xingyu Zhou and Alvin Ho Kwan Cheung and Qinyao Wei and Jing Ren and Xiang Zhang and Qing Li and Yongzhan Nie and Jun Yu},
title = {Dietary nitrate drives gastritis by modulating gastric microbiota and metabolites},
year = {2026},
journal = {Cancer Biology & Medicine},
volume = {23},
number = {5},
pages = {717-736},
keywords = {Nitrate diet, gastritis, Enterococcus gallinarum, 5-HIAA, germ-free mouse},
url = {https://www.sciopen.com/article/10.20892/j.issn.2095-3941.2025.0679},
doi = {10.20892/j.issn.2095-3941.2025.0679},
abstract = {ObjectiveDietary 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.MethodsAnimals 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.ResultsNaD induced gastritis in conventional mice compared to ND-fed mice. In addition, NaD incited the infiltration of macrophages and neutrophils with elevated levels of inflammatory cytokine genes (IL-17a, Ccl20, Cxcl5, IL-6, and Ccl2). A significant shift in the composition of the gastric microbiota occurred with an increase in pathogenic bacteria (Enterococcus gallinarum, Prevotella timonensis, and Mycobacterium gordona) and a decrease in probiotics (Roseburia hominis, Clostriduim scindens, and Faecalibacterium prausnitzii). Furthermore, NaD induced alterations in the metabolic profile, marked by an elevated level of 5-hydroxyindoleacetate (5-HIAA), a key downstream metabolite of the tryptophan metabolic pathway. Notably, 5-HIAA also upregulated the levels of inflammatory cytokines in the human gastric epithelial GES-1 cell line. In addition, both E. gallinarum colonization and 5-HIAA exposure significantly increased inflammatory responses in conventional and germ-free mouse models.ConclusionsNaD drives gastritis in mice by inducing gastric microbial dysbiosis and metabolomic dysregulation with elevated 5-HIAA.}
}