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The overuse and misuse of antibiotics have accelerated the selection of antibiotic-resistant bacteria, significantly impacting human, animal, and environmental health. As aquatic environments are vulnerable to antibiotic resistance, suitable management practices should be adopted to tackle this phenomenon. Here we show an effective, nature-based solution for reducing antibiotic resistance from actual wastewater. We utilize a bioreactor that relies on benthic (biofilms) and planktonic microbial communities to treat secondary effluent from a small urban wastewater treatment plant (<10,000 population equivalent). This treated effluent is eventually released into the local aquatic ecosystem. We observe high removal efficiency for genes that provide resistance to commonly used antibiotic families, as well as for mobile genetic elements that could potentially aid in their spread. Importantly, we notice a buildup of sulfonamide ( sul1 and sul2 ) and tetracycline ( tet(C) , tet(G) , and tetR ) resistance genes specifically in biofilms. This advancement marks the initial step in considering this bioreactor as a nature-based, cost-effective tertiary treatment option for small UWWTPs facing antibiotic resistance challenges., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Society for Environmental Sciences, Harbin Institute of Technology, Chinese Research Academy of Environmental Sciences.)