This study aimed to evaluate the nutrient removal and microbial response during the treatment of antibiotics-enriched swine wastewater by vertical flow constructed wetlands with different water flow directions and substrates. Better NH4-N and TN removal were achieved in down-flow and up-flow treatments, respectively. The concentrations of all the chemical properties including oxytetracycline (OTC), difloxacin (DIF), copper (Cu) and zinc (Zn), nitrite/nitrate, sulphate and total organic carbon (TOC) in down-flow treatment soils were significantly higher than those in up-flow treatments on day 30, 60 and 90 (p < 0.05). Bacterial alpha-diversity indices in soils were negatively correlated with the concentrations of OTC, DIF, Cu and Zn significantly (p < 0.05). Among experimental factors, substrate type significantly contributed to variation of bacterial communities in waters, while water flow direction and sampling time significantly contributed to those in soils (p < 0.01). Among environmental factors, OTC + DIF, Cu + Zn, nitrate/nitrite and sulphate significantly contributed to variation of bacterial communities in soils (p < 0.05). The taxonomy assignment indicated that antibiotics accumulation in soils promoted the growth of 19 dominant genera, including several antibiotic-resistant or degrading bacteria, which however were generally not dominant in effluents. In addition, although the TN and NH4-N removals were reduced when antibiotic concentrations in soils increased, the available community data cannot strongly support the inhibition effect of antibiotics on nitrogen transformation. Further assessment found that some dominant genera in water samples and those enriched under the stress of antibiotics in soils tended to increase their abundances in the effluents of oyster shell-based CWs. (C) 2017 Elsevier B.V. All rights reserved.