Differential effects of antibiotic exposure on gut microbiota homeostasis and functional dynamics in a stable...

The composition and function of human gut microbiota are influenced by antibiotics; however, the real-time dynamic effects of different antibiotic classes have remained elusive due to ethical constraints. In this study, a stable, long-term, continuous simulated intestinal culture system was established to evaluate the impacts exerted by three antibiotics, amoxicillin, ciprofloxacin, and ceftriaxone sodium, on gut microbial homeostasis, composition, and function. As indicated by the results, amoxicillin and ciprofloxacin increased the abundance of antibiotic resistance genes (ARGs), with concurrent increases in Escherichia coli and Prevotella_9 to 83.53% and 51.02%, respectively. Ceftriaxone sodium induced an approximately 70-fold surge in ARGs, which returned to baseline after withdrawal of the drug. Metabolomic analysis revealed downregulation of lipid and tryptophan metabolism but upregulation of porphyrin metabolism following exposure to all three antibiotics. Functional gene analysis indicated increased levels of patA and lmrD to 0.025% and 0.01% following treatment with ciprofloxacin and amoxicillin treatment, respectively. Furthermore, ciprofloxacin triggered the overexpression of evgS in Escherichia coli. The Microbial Dynamical Systems INference Engine (MDSINE) algorithm model predicted that the effects on microbiota composition from amoxicillin and ciprofloxacin were irreversible, but those from ceftriaxone sodium were restored. These findings emphasize the impacts exerted by different antibiotics on gut microbiota and underscore the need for judicious antibiotic selection for minimizing irreversible ecological damage.