为防断奶仔猪腹泻和促生长，饲料中添加抗生素和高铜、锌是常用的营养策略。铜、锌是宿主细胞和肠道细菌正常生长所必须，但是高水平的铜、锌却能杀菌并诱导细菌产生抗性应答。肠道细菌重金属抗性与抗生素耐药性的关系如何？饲料高铜、锌是否加剧了断奶仔猪肠道细菌的耐药问题，寻求控制肠道耐药菌产生的有效营养措施是本研究的目的和意义所在。断奶仔猪分为四组，分别饲喂无抗低铜、锌日粮、有抗（恩诺沙星）低铜、锌日粮、无抗高铜、锌日粮和有抗高铜、锌日粮，采集粪便分析恩诺沙星和高铜、锌引起的菌群结构和耐药、重金属抗性基因变化；分离并测定大肠杆菌和粪肠球菌的抗生素和铜、锌敏感性，以阐明饲料抗生素和高铜、锌在肠道细菌抗生素耐药性形成中的协同作用。体外培养不同敏感型大肠杆菌和粪肠球菌，分析恩诺沙星和高铜、锌引起的外排泵基因、外膜蛋白基因、parC基因、tcrB基因等表达量的变化，探讨高铜、锌和抗生素协同诱导耐药应答的可能机制。

In order to prevent diarrhea and to promote growth of weaning piglets, antibiotics, copper and zinc were supplemented into feed. Copper and zinc is essential trace element required for vital biological functions in both prokaryotic and eukaryotic cells. However, copper and zinc in excess concentrations are toxic to cells because they induce the production of intracellular reactive oxygen radicals, which inactivate cell components such as nucleic acids, lipids, and proteins. Therefore, cells tightly regulate intracellular copper and zinc concentrations to avoid toxicity. To survive, many bacterial species have developed copper resistance. Acquired copper resistance mediated by the plasmid-localized tcrB gene has been described for E. faecium and E. faecalis isolated from both production animal and humans in several European countries. A close genetic link between tcrB and glycopeptide-resistance (vanA) has been demonstrated for E. faecium. The objective of this study is to describe the relationship between metal-resistance and antibiotic-resistance for gut microbiota of weaned piglets, to answer whether in-feed copper and zinc at high concentrations could drive co-selection of antibiotic resistance in piglets' gut. 48 of weaned piglets will be divided into four groups, control group 1 (copper and zinc at low concentrations without antibiotic), control group 2 (copper and zinc at low concentrations with antibiotic), treatment group 1 (copper and zinc at high concentrations without antibiotic), and treatment group 2 (copper and zinc at high concentrations with antibiotic). Fecal samples will be used to analyze the effect of in-feed antibiotic, copper and zinc on composition, metal-resistance gene and antibiotic-resistance gene levels of gut microbiota. Isolated and identified E. coil and E. faecium will be used to determine antibiotic susceptibility, copper and zinc susceptibility, tcrB gene and parC gene. The tcrB-positive/ negative, and tcrB-positive/ negative E. coil /E. faecium will be incubated in vitro to demonstrate the co-selection of antibiotic and metal resistance.