摘要
      抗生素在密集型海水养殖行业中被广泛使用。迫切需要更好地了解抗生素对生物体代际抗生素耐药性的影响，因为代际传播对抗生素耐药性基因（ARGs）在环境中的传播至关重要。在本文中，长期暴露于低剂量磺胺二甲嘧啶（SMZ）的海洋花呢（Oryzias melastigma）会对后代产生激素影响，其特征是粪便微生物群的丰富性和多样性增加以及肠道屏障相关基因上调。由于F1胚胎中没有显著的SMZ积累，后代免疫受到遗传因素的调节和引起。此外，后代中的一些顶级属与免疫疾病呈正相关，而一些免疫相关基因，如TNFα、IL1R2和TLR3的表达发生了显著变化。这进一步表明，由后代免疫力变化引起的宿主选择可能是后代肠道微生物定植的主要决定因素。宏基因组分析显示，变形杆菌是ARGs的主要携带者，而亲代SMZ暴露通过促进γ-变形杆菌和拟杆菌的多样性，促进了参与抗生素失活的多种ARGs在后代中的分布和富集，进一步说明抗生素选择压力持续存在，即使后代没有暴露。因此，SMZ以增加抗生素耐药性为代价，在后代中诱导了兴奋。总之，这些发现全面概述了抗生素的代际效应，并提醒我们，抗生素对生物体的代际影响所引起的ARG传播不应被忽视。
Abstract
Antibiotics are widely consumed in the intensive mariculture industry. A better understanding of the effect of antibiotics on intergenerational antibiotic resistance in organisms is urgent since intergenerational transmission is crucial for the spread of antibiotic resistance genes (ARGs) in the environment. Herein, marine medaka (Oryzias melastigma) chronically exposed to low doses of sulfamethazine (SMZ) hormetically affected the progeny, characterized by increased richness and diversity of fecal microbiota and intestinal barrier-related gene up-regulation. Progeny immunity was modulated and caused by genetic factors due to the absence of significant SMZ accumulation in F1 embryos. In addition, some of the top genera in the progeny were positively correlated with immune diseases, while the expression of some immune-related genes, such as TNFα, IL1R2, and TLR3 changed significantly. This further indicated that the host selection caused by changes in progeny immunity was probably the primary determinant of progeny intestinal microbial colonization. Metagenomic analysis revealed that Proteobacteria represented the primary carriers of ARGs, while parental SMZ exposure facilitated the distribution and enrichment of multiple ARGs involved in the antibiotic inactivation in the progeny by promoting the diversity of Gammaproteobacteria and Bacteroidetes, further illustrating that antibiotic selection pressure persisted even if the offspring were not exposed. Therefore, SMZ induced hormesis in the progeny at the expense of increasing antibiotic resistance. Collectively, these findings provide a comprehensive overview of the intergenerational effect of antibiotics and serve as a reminder that the ARG transmission induced by the intergenerational impact of antibiotics on organisms should not be ignored.

https://www.sciencedirect.com/science/article/abs/pii/S0045653522032313