Abstract
β-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 β-lactam antibiotics and contributes to the etiology of inflammatory bowel disease (IBD). In this study, the influence of amoxicillin (AMO) on Klebsiella 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 Klebsiella and enhanced serum resistance, antibiotic resistance, and biofilm formation ability of Klebsiella variicola (K. variicola) compared to the wild-type strain in the control group mice. Colonization of mice with the AMO-associated K. variicola could induce Th1 cells and inhibit Treg differentiation to promote inflammation in ABx murine model. In addition, inoculation of AMO-associated K. variicola in dextran sodium sulfate (DSS)-induced colitis murine model mice also confirmed that K. variicola 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 Klebsiella virulence in mice by disrupting the T cell equilibrium to exacerbate colitis, thereby providing a reference for proper antibiotic prescription.
Highlights
The gut microbiota has been recognized as being indispensable for maintaining host homeostasis via nutrient production and processing and immune system training (Samuli et al, 2012)
The Antibiotic Resistance and Virulence of K. variicola Are Enhanced in AMO-Treated Mice
The results showed that K. variicola Z5 significantly increased the proportion of Th1 cells in the spleens, blood, mesenteric lymph nodes (MLNs), and cervical lymph nodes (CLNs) compared to that observed in the control group (P < 0.05), potentially exacerbating inflammation (Figures 5A,B)
Summary
The gut microbiota has been recognized as being indispensable for maintaining host homeostasis via nutrient production and processing and immune system training (Samuli et al, 2012). Amoxicillin-Associated Klebsiella Drives Inflammation to alter the composition and function of the gut microbiota and upregulate the expression of antibiotic resistance genes (ARGs) and affect health by causing asthma, allergies, diarrhea, obesity, diabetes, and inflammatory bowel diseases (IBDs) in both early life and adulthood (Lewis and Pamer, 2017; Ni et al, 2017; Mccoy et al, 2018). Recent studies found that AMO disrupted the gut microbiota and induced ARGs that may increase the healthy risk (Korry et al, 2020; Wang et al, 2020). An adequate understanding of the relationship between the effects of antibiotics toward specific bacteria and the paradigm of such alterations in associated disease pathogenesis remains lacking
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