摘要
      抗菌药物的广泛使用推动了病原微生物耐药性的演变，抗菌耐药性基因（ARGs）的流行率增加，并通过水平基因转移（HGT）在物种间传播。然而，对与人体相关的更广泛的共生微生物群落——微生物组——的影响还不太清楚。小规模研究已经确定了抗生素消费的短暂影响，但我们对8972个宏基因组中的ARGs进行了广泛的调查，以确定群体水平的影响。重点研究了3096个未服用抗生素的健康个体的肠道微生物群，我们证明了ARG的总丰度和多样性与横跨三大洲的十个国家的人均抗生素使用率之间的高度显著相关性。来自中国的样本是显著的异常值。我们收集了154723个人类相关宏基因组组装基因组（MAG），将这些ARG与分类群联系起来，并检测HGT。这表明，ARG丰度的相关性是由病原体和共生体之间共享的多物种移动ARG驱动的，在MAG和ARG网络的高度连接的中心组成部分内。我们还观察到，个体人类肠道ARG图谱分为两种类型或抗性类型。频率较低的抗性类型具有较高的总ARG丰度，与某些类型的抗性有关，并与ARG网络外围变形杆菌中的物种特异性基因有关。
Abstract
The widespread usage of antimicrobials has driven the evolution of resistance in pathogenic microbes, both increased prevalence of antimicrobial resistance genes (ARGs) and their spread across species by horizontal gene transfer (HGT). However, the impact on the wider community of commensal microbes associated with the human body, the microbiome, is less well understood. Small-scale studies have determined the transient impacts of antibiotic consumption but we conduct an extensive survey of ARGs in 8972 metagenomes to determine the population-level impacts. Focusing on 3096 gut microbiomes from healthy individuals not taking antibiotics we demonstrate highly significant correlations between both the total ARG abundance and diversity and per capita antibiotic usage rates across ten countries spanning three continents. Samples from China were notable outliers. We use a collection of 154,723 human-associated metagenome assembled genomes (MAGs) to link these ARGs to taxa and detect HGT. This reveals that the correlations in ARG abundance are driven by multi-species mobile ARGs shared between pathogens and commensals, within a highly connected central component of the network of MAGs and ARGs. We also observe that individual human gut ARG profiles cluster into two types or resistotypes. The less frequent resistotype has higher overall ARG abundance, is associated with certain classes of resistance, and is linked to species-specific genes in the Proteobacteria on the periphery of the ARG network.

https://www.nature.com/articles/s41467-023-36633-7