Colonization of Mice With Amoxicillin-Associated Klebsiella variicola Drives Inflammation via Th1 Induction and Treg Inhibition

Abstract

β-Lactam antibiotics can increase the resistance and virulence of individual intestinal microorganisms, which may affect host physiology and health. <i>Klebsiella</i>, a crucial gut inhabitant, has been confirmed to be resistant to most β-lactam antibiotics and contributes to the etiology of inflammatory bowel disease (IBD). In this study, the influence of amoxicillin (AMO) on <i>Klebsiella</i> and 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 of <i>Klebsiella</i> and enhanced serum resistance, antibiotic resistance, and biofilm formation ability of <i>Klebsiella variicola</i> (<i>K. variicola</i>) compared to the wild-type strain in the control group mice. Colonization of mice with the AMO-associated <i>K. variicola</i> could induce Th1 cells and inhibit Treg differentiation to promote inflammation in ABx murine model. In addition, inoculation of AMO-associated <i>K. variicola</i> in dextran sodium sulfate (DSS)-induced colitis murine model mice also confirmed that <i>K. variicola</i> colonization exacerbated inflammation as assessed by increased TNF-α, IFN-γ, 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 enhances <i>Klebsiella</i> virulence in mice by disrupting the T cell equilibrium to exacerbate colitis, thereby providing a reference for proper antibiotic prescription.