ATPIF1 Deficiency Significantly Alleviates Citrobacter rodentium-Induced Colitis in Mice.

Mitochondrial ATP synthase inhibitory factor 1 (ATPIF1) regulates cellular energy metabolism and has been implicated in inflammatory disorders. However, its role in infection-associated colitis remains unclear. This study aimed to investigate the effects of ATPIF1 on host susceptibility and inflammation in a Citrobacter rodentium-induced infectious colitis model. 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, histopathology, barrier function, inflammatory markers, and gut microbiota were assessed using standard approaches, including immunohistochemistry, RT-qPCR, Western blotting, and 16S rRNA sequencing. 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 reduced activation of the NLRP3 inflammasome pathway, although whether this is a direct effect remains unclear. Microbiota analysis also revealed that ATPIF1 deficiency stabilized microbiota composition and reduced pathogenic expansion. ATPIF1 deficiency exhibited a protective phenotype in C. rodentium-induced colitis, accompanied by reduced inflammation, preserved barrier function, enhanced pathogen clearance, and stabilized microbiota composition. ATPIF1 may represent a potential therapeutic target in infection-associated colitis.