Colonization of Mice With Amoxicillin-AssociatedKlebsiella variicolaDrives Inflammation via Th1 Induction and Treg Inhibition

beta-Lactam antibiotics can increase the resistance and virulence of individual intestinal microorganisms, which may affect host physiology and health.Klebsiella, a crucial gut inhabitant, has been confirmed to be resistant to most beta-lactam antibiotics and contributes to the etiology of inflammatory bowel disease (IBD). In this study, the influence of amoxicillin (AMO) onKlebsiellaand its role in colitis was investigated in an antibiotic cocktail (ABx) murine model. The results suggested that a 7-day AMO treatment significantly enriched the abundance ofKlebsiellaand enhanced serum resistance, antibiotic resistance, and biofilm formation ability ofKlebsiella variicola(K. variicola) compared to the wild-type strain in the control group mice. Colonization of mice with the AMO-associatedK. variicolacould induce Th1 cells and inhibit Treg differentiation to promote inflammation in ABx murine model. In addition, inoculation of AMO-associatedK. variicolain dextran sodium sulfate (DSS)-induced colitis murine model mice also confirmed thatK. variicolacolonization exacerbated inflammation as assessed by increased TNF-alpha, IFN-gamma, IL-17a, and disease activity (DAI) levels; decreased colon length and bodyweight; and a disrupted Th1/Treg balance. The results of our study demonstrate that AMO enhancesKlebsiellavirulence in mice by disrupting the T cell equilibrium to exacerbate colitis, thereby providing a reference for proper antibiotic prescription.