ATPIF1 deficiency Significantly Alleviates Citrobacter rodentium-Induced Ulcerative Colitis in Mice

Background Mitochondrial ATP synthase inhibitory factor 1 (ATPIF1) is a crucial regulator of cellular energy metabolism and has been implicated in inflammatory disorders. However, its role in bacterial infection-driven ulcerative colitis (UC) remains unclear. Purpose This study aimed to investigate the effects of ATPIF1 on host susceptibility and inflammatory responses in a Citrobacter rodentium -induced infectious colitis model. Methods ATPIF1 knock out (KO) and wild type (WT) mice were orally gavaged with C. rodentium to induce infectious colitis. Body weight, disease activity index (DAI), and colon length were recorded. Histopathology, Alcian blue staining, and immunohistochemistry were performed to assess mucosal integrity and barrier function. Inflammatory responses were evaluated through immunohistochemistry, RT-qPCR, and Western blotting, while gut microbiota composition was analyzed via 16S rRNA gene sequencing. Results ATPIF1 deficiency alleviated C. rodentium -induced colitis, as evidenced by reduced weight loss, lower DAI scores, and attenuated colon shortening. KO mice preserved epithelial architecture, exhibited increased numbers of goblet cells and ZO-1 mRNA expression, indicating an intact mucosal barrier. Furthermore, KO mice showed reduced infiltration of inflammatory cells, decreased expression of IL-1β and TNF-α, and suppressed activation of the NLRP3 inflammasome pathway. Microbiota analysis also revealed that ATPIF1 deficiency stabilized bacterial community composition and reduced pathogenic expansion. Conclusion ATPIF1 deficiency significantly alleviates C. rodentium -induced colitis by mitigating inflammation, preserving mucosal barrier function, promoting pathogen clearance, and stabilizing gut microbiota. These findings suggest that ATPIF1 may represent a potential therapeutic target for infection-associated UC.