Antibiotic-resistant pathogens constitute an escalating public health concern. Hence a better understanding of the underlying processes responsible for this expansion is urgently needed. Co-selection of heavy metal/biocide and antibiotic resistance genes (ARGs) has been suggested as one potential mechanism promoting the proliferation of antimicrobial resistance (AMR). This paper aims to elucidate this interplay and exploit differences in antibiotic usage to infer patterns of co-selection by the non-antibiotic factors metals and biocides in the context of pig farming. We examined 278 gut metagenomes from pigs with continuous antibiotic exposure, only at weaning and at no exposure. Metals as growth promoters and biocides as disinfectants are currently used with little restrictions in stock farming. The pigs under continuous antibiotic exposure displayed the highest co-occurrence of ARGs and other genetic elements while the pigs under limited use of antibiotics still showed abundant co-occurrences. Pathogens belonging to Enterobacteriaceae displayed increased co-occurrence phenomena, suggesting that this maintenance is not a random selection process from a mobilized pool but pertains to specific phylogenetic clades. These results suggest that metals and biocides displayed strong selective pressures on ARGs exerted by intensive farming, regardless of the current use of antibiotics.

耐抗生素病原体构成了一个不断升级的公共卫生问题。因此，迫切需要更好地了解导致这种扩展的基本过程。重金属/杀菌剂和抗生素抗性基因 (ARGs) 的共同选择已被认为是促进抗微生物药物耐药性 (AMR) 扩散的一种潜在机制。本文旨在阐明这种相互作用，并利用抗生素使用的差异来推断非抗生素因素金属和杀生物剂在养猪业中的共同选择模式。我们检查了来自持续暴露于抗生素的猪的 278 个肠道宏基因组，仅在断奶时和未暴露时。目前在畜牧业中使用金属作为生长促进剂和杀菌剂作为消毒剂，几乎没有限制。持续接触抗生素的猪表现出最高的 ARGs 和其他遗传元素的共现率，而有限使用抗生素的猪仍然表现出大量的共现。病原体属于肠杆菌科显示出增加的共现现象，表明这种维持不是从动员池中随机选择的过程，而是与特定的系统发育进化枝有关。这些结果表明，无论当前使用抗生素如何，金属和生物杀灭剂对集约化农业施加的 ARGs 表现出很强的选择压力。