Fusobacterium nucleatum exacerbates chronic atrophic gastritis in rats via mitochondrial dysfunction and inflammatory activation

Chronic atrophic gastritis (CAG) is a premalignant condition with limited therapeutic strategies. The role of the oral pathogen Fusobacterium nucleatum ( F. nucleatum ), associated with gastrointestinal carcinogenesis, in CAG remains unclear. This study investigated whether F. nucleatum aggravates gastric mucosal injury through inflammation and mitochondrial dysfunction in CAG. A rat model of CAG was induced using N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) for 10 weeks, combined with oral gavage of F. nucleatum . Gastric pathology, bacterial colonization, serum cytokine levels, and mitochondrial membrane potential were evaluated. In vitro, human gastric epithelial cells (GES-1) were treated with MNNG and co-cultured with F. nucleatum at multiplicities of infection (MOI) of 50, 100, or 150. Cytokine concentrations in cell culture supernatants were quantified using corresponding human enzyme-linked immunosorbent assay kits. Mitochondrial membrane potential was assessed via flow cytometry. F. nucleatum colonized gastric tissues and intensified MNNG-induced injury, including rugal flattening, glandular atrophy, intestinal metaplasia, and inflammatory cell infiltration. It significantly increased pro-inflammatory cytokine levels and further decreased mitochondrial membrane potential. In GES-1 cells, F. nucleatum dose-dependently elevated secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and impaired mitochondrial function. F. nucleatum exacerbates CAG by promoting gastric inflammation and mitochondrial dysfunction. These findings may underscore the microbiota–mitochondria axis as a potential therapeutic target to prevent CAG progression.