Toxicity Assessment of Nano-ZnO Exposure on the Human Intestinal Microbiome, Metabolic Functions, and Resistome Using an In Vitro Colon Simulator

Nano-ZnO, as a commonly used nanomaterial, has been found in drinking water, food, and medicine; therefore, it poses potential health risks via the digestion system. However, little is known about the toxicity of nano-ZnO on the human intestinal microbiome, which plays critical roles in human health. This study comprehensively investigated the impact of nano-ZnO on the human gut microbiome, metabolic functions, and resistome using an in vitro colon simulator. Nano-ZnO induced concentration-dependent decreases in the production of short-chain fatty acids (SCFAs). Metagenomic analysis revealed that nano-ZnO not only led to dose-dependent shifts in the composition and diversity of the gut microbiota but also changed the key functional pathways of the gut microbiome. Although the diversity of the gut microbiota basically recovered after stopping exposure to nano-ZnO, SCFAs still showed a concentration-dependent decrease. Furthermore, although a medium concentration of nano-ZnO (2.5 mg/L) reduced the abundance of many antibiotic resistance genes (ARGs) by inhibiting the growth of related host bacteria, a low concentration of nano-ZnO (0.1 mg/L) greatly enriched the abundance of tetracycline resistance genes. Our findings provide evidence that nano-ZnO can impact the diversity, metabolism, and functional pathways of the human gut microbiome, as well as the gut resistome, highlighting the potential health effects of nanoparticles.

纳米氧化锌（Nano-ZnO）作为一种常用纳米材料，已在饮用水、食品及药品中被检出，因此可通过消化系统对人体健康构成潜在风险。然而，目前对于纳米氧化锌对人类肠道微生物组的毒性作用尚不清楚，而肠道微生物组对人体健康发挥着至关重要的作用。本研究采用体外结肠模拟系统，全面探究了纳米氧化锌对人类肠道微生物组、代谢功能以及耐药组（resistome）的影响。纳米氧化锌可诱导短链脂肪酸（short-chain fatty acids，SCFAs）的生成呈现浓度依赖性降低。宏基因组学分析表明，纳米氧化锌不仅会导致肠道菌群的组成与多样性呈现剂量依赖性变化，还会改变肠道微生物组的关键功能通路。尽管停止暴露于纳米氧化锌后，肠道菌群的多样性基本恢复，但短链脂肪酸的生成仍呈现浓度依赖性降低。此外，尽管中等浓度的纳米氧化锌（2.5 mg/L）可通过抑制相关宿主菌的生长，降低多种抗生素抗性基因（antibiotic resistance genes，ARGs）的丰度，但低浓度纳米氧化锌（0.1 mg/L）却会显著富集四环素抗性基因的丰度。本研究结果证实，纳米氧化锌可影响人类肠道微生物组的多样性、代谢功能与功能通路，同时也会改变肠道耐药组，凸显了纳米颗粒潜在的健康影响。