Long-term use of ceftriaxone sodium induced changes in gut microbiota and immune system

Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities. Previous studies have all focused on the effects of short term use of antibiotics. Here, we focus on the effects of long term use of antibiotic on gut microbiota and immunity. BALB/c mice received saline or different doses of ceftriaxone sodium (100, 200 and 400 mg/mL) via daily gavage for 150 days. Alterations of fecal microbiota, small intestine histopathology, body weight, spleen index, serum IgG, mucus SIgA, IFN-γ/IL-4 ratio, CD4/CD8 ratio and CD4⁺CD25⁺ cells were evaluated. Long term ceftriaxone sodium administration resulted in gut microbiota dysbiosis, intestine histological lesions, growth inhibition, spleen index reducing. The immune defense ability reduced as serum IgG and mucus SIgA decreased significantly. Not only the immune defense, long term ceftriaxone administration also affected immune regulation. The IFN-γ/IL-4 and CD4/CD8 ratios increased, the CD4⁺CD25⁺ cells reduced on days 30 and 60 after ceftriaxone administration. However, after 90 days of ceftriaxone administration, the IFN-γ/IL-4, CD4/CD8 ratios and CD4⁺CD25⁺ cells restored, which indicated a new balance of immune regulation had been formed. Overall, these findings contribute to our understanding of long term antibiotic administration influencing gut microbiota and immunity.