Macleaya cordata extract, an antibiotic alternative, does not contribute to antibiotic resistance gene dissemination.

The abuse of antibiotics and their associated health risks are receiving global attention. The use of antibiotic additives in fodder has been banned in the European Union since 2006 and in China since 2020. Antibiotic alternatives are being developed, but their risks to the soil ecosystem remain poorly understood. Here, we compared the effects of the antibiotic oxytetracycline (OTC10, 10 mg/kg) with those of a Macleaya cordata extract (MCE, 10 and 100 mg/kg), the major antibiotic substitute. All tested concentrations of MCE and OTC10 exerted slight effects on the soil microbiome, but OTC10 and MCE100 could interfere with the structures and functions of the gut microbiome and might thus affect the soil ecological functions of Enchytraeus crypticus. Furthermore, OTC10 exposure inevitably increased the antibiotic resistance gene (ARG) abundance by 213%, whereas MCE did not induce ARG dissemination, which explains why MCE is considered to be associated with a low ecological risk. Our research provides the first demonstration of the risks posed by antibiotic alternatives to soil animals from the perspective of environmental toxicology and explores the potential development of antibiotic alternatives associated with a low ecological risk from a new perspective.