Aspirin altered antibiotic resistance genes response to sulfonamide in the gut microbiome of zebrafish

Pharmaceuticals are widespread in aquatic environments and might contribute to the prevalence of antibiotic resistance. However, the co-effect of antibiotics and non-antibiotic pharmaceuticals on the gut microbiome of fish is poorly understood. In this study, we characterized the variation of the zebrafish gut microbiome and resistome after exposure to sulfamethoxazole (SMX) and aspirin under different treatments. SMX contributed to the significant increase in the antibiotic resistance genes (ARGs) richness and abundance with 46 unique ARGs and five mobile genetic elements (MGEs) detected. Combined exposure to SMX and aspirin enriched total ARGs abundance and rearranged microbiota under short-term exposure. Exposure time was more responsible for resistome and the gut microbiome than exposure concentrations. Perturbation of the gut microbiome contributed to the functional variation related to RNA processing and modification, cell motility, signal transduction mechanisms, and defense mechanisms. A strong significant positive correlation (R = 0.8955, p < 0.001) was observed between total ARGs and MGEs regardless of different treatments revealing the key role of MGEs in ARGs transmission. Network analysis indicated most of the potential ARGs host bacteria belonged to Proteobacteria. . Our study suggested that co-occurrence of non-antibiotics and antibiotics could accelerate the spread of ARGs in gut microbial communities and MGEs played a key role.