Changes in the mammalian gut microbiome are linked to the impairment of immunological function and numerous other pathologies. Antimicrobial silver nanoparticles (AgNPs) are incorporated into numerous consumer products (e.g., clothing, cosmetics, food packaging), which may directly impact the gut microbiome through ingestion. The human health impact of chronic AgNP ingestion is still uncertain, but evidence from exposure to other antimicrobials provides a strong rationale to assess AgNP effects on organ function, immunity, metabolism, and gut-associated microbiota. To investigate this, mice were gavaged daily for 5 weeks with saline, AgNPs, antibiotics (ciprofloxacin and metronidazole), or AgNPs combined with antibiotics. Animals were weighed daily, assessed for glucose tolerance, organ function, tissue and blood cytokine and leukocyte levels. At the end of the study, we used 16S rDNA amplicon and whole-metagenome shotgun sequencing to assess changes in the gut microbiome. In mice exposed to both AgNPs and antibiotics, silver was found in the stomach, and small and large intestines, but negligible amounts were present in other organs examined. Mice exposed to AgNPs alone showed minimal tissue silver levels. Antibiotics, but not AgNPs, altered glucose metabolism. Mice given AgNPs and antibiotics together demonstrated slower weight gain, reduced peripheral lymphocytes, and elevated splenic, but not circulatory markers of inflammation. 16S rDNA profiling of cecum and feces and metagenomic sequencing of fecal DNA demonstrated that combined AgNP-antibiotic treatment also significantly altered the structure and function of the gut microbiota, including depletion of the indicator species Akkermansia muciniphila. This study provides evidence for possible biological effects from repeated ingestion of AgNP-containing consumer products when antibiotics are also being used and raises concern that an impaired gut microbiome (e.g., through antibiotic use) can potentiate the harm from chemical exposures such as AgNPs.

哺乳动物肠道微生物组的变化与免疫功能受损和许多其他疾病有关。抗菌银纳米粒子 (AgNPs) 被掺入许多消费品（例如服装、化妆品、食品包装）中，它们可能通过摄入直接影响肠道微生物组。长期摄入 AgNP 对人类健康的影响仍不确定，但来自暴露于其他抗菌剂的证据为评估 AgNP 对器官功能、免疫、新陈代谢和肠道相关微生物群的影响提供了强有力的依据。为了研究这一点，每天用盐水、AgNPs、抗生素（环丙沙星和甲硝唑）或 AgNPs 与抗生素联合对小鼠进行灌胃 5 周。每天对动物称重，评估葡萄糖耐量、器官功能、组织和血液细胞因子和白细胞水平。在研究结束时，我们使用 16S rDNA 扩增子和全宏基因组鸟枪法测序来评估肠道微生物组的变化。在暴露于 AgNPs 和抗生素的小鼠中，在胃、小肠和大肠中发现了银，但在检查的其他器官中存在的量可以忽略不计。仅暴露于 AgNPs 的小鼠表现出最低的组织银水平。抗生素，但不是 AgNPs，改变了葡萄糖代谢。给予 AgNPs 和抗生素的小鼠体重增加较慢，外周淋巴细胞减少，脾脏升高，但循环炎症标志物没有。盲肠和粪便的 16S rDNA 分析和粪便 DNA 的宏基因组测序表明，联合 AgNP 抗生素治疗也显着改变了肠道微生物群的结构和功能，包括指示物种的消耗Akkermansia muciniphila。这项研究为在同时使用抗生素的情况下重复摄入含 AgNP 的消费品可能产生的生物学效应提供了证据，并引起了人们对肠道微生物组受损（例如，通过使用抗生素）可能会加剧化学暴露（如 AgNPs）的危害的担忧。