Effects of Levofloxacin Exposure on Intestinal Microbes of Zebrafish

doi:10.16258/j.cnki.1674-5906.2025.04.009

Ecology and Environment ›› 2025, Vol. 34 ›› Issue (4): 593-607.DOI: 10.16258/j.cnki.1674-5906.2025.04.009

• Research Article【Environmental Science】 • Previous Articles Next Articles

Effects of Levofloxacin Exposure on Intestinal Microbes of Zebrafish

ZHANG Yaping¹^,^*(), MO Cuiling¹, LI Yingpeng², XU Ke¹

1. College of Harbour and Coastal Engineering, Jimei University, Xiamen 361021, P. R. China
2. Fisheries College, Jimei University, Xiamen 361021, P. R. China

Received:2024-10-18 Online:2025-04-18 Published:2025-04-24
Contact: ZHANG Yaping

左氧氟沙星暴露对斑马鱼肠道微生物的影响

张亚平¹^,^*(), 莫璀玲¹, 李迎鹏², 徐棵¹

1.集美大学港口与海岸工程学院，福建厦门 361021
2.集美大学水产学院，福建厦门 361021

通讯作者: 张亚平
作者简介:张亚平（1978年生），教授，博士，主要从事环境科学与工程技术研究。E-mail: ypzhang@jmu.edu.cn
基金资助:
国家自然科学基金项目(21978246);国家自然科学基金项目(22478119);福建省自然科学基金项目(2014J01050)

Abstract

Abstract:

Levofloxacin is widely used in aquaculture, animal husbandry, veterinary medicine, and in human health as an antibiotic drug. This is a typical representation of a PPCPs. With the development and deepening of research on intestinal microbes, increasing evidence has shown that PPCPs can cause various diseases by disrupting gut microbiota homeostasis. Therefore, there is an urgent need to explore the relationship between levofloxacin and intestinal microbial homeostasis as well as the impact of levofloxacin on intestinal microbes. This study aimed to explore the effects of levofloxacin on the intestinal microbes of zebrafish and the resulting toxicity. Adult zebrafish were exposed to environmentally relevant concentrations of levofloxacin (0, 10 μg·L⁻¹, 100 μg·L⁻¹, 1 mg·L⁻¹, 10 mg·L⁻¹, and 100 mg·L⁻¹) for 10 days, after which the morphological changes in zebrafish intestinal tissue were analyzed. The composition of the intestinal flora was analyzed using paraffin sectioning, HE staining, and 16S rDNA high-throughput sequencing. The results showed that zebrafish intestinal tissue sections revealed disordered intestinal gland structure, erosion of the mucosal layer, shedding of villi, and an increased number of inflammatory cells. These damaging effects increased with increasing concentrations of levofloxacin. 16S rDNA high-throughput sequencing revealed that the abundances of Actinobacteria, Firmicutes, Bacteroidetes, and Proteobacteria in the intestinal bacteria of zebrafish decreased to 70% of that in the control group, and the microbial diversity index decreased significantly compared to that in the control group. In summary, levofloxacin can cause significant intestinal damage, immune and metabolic dysfunction, and other toxic effects in zebrafish, thereby reducing the abundance and diversity of the intestinal flora. This study provides a deeper understanding of the mechanisms underlying levofloxacin-induced gut toxicity, and offers a theoretical reference for the rational use of levofloxacin.

Key words: levofloxacin, zebrafish, intestinal flora, intestinal homeostasis, environmental toxicology, antibiotic

摘要： 左氧氟沙星作为一种抗生素类药物，在水产养殖、畜牧兽医、人类健康等方面应用广泛，属于药物与个人护理用品（PPCPs）的一种典型代表物。随着肠道微生物相关研究的开展与不断深入，越来越多的证据表明，PPCPs可以通过干扰肠道微生物稳态来造成各种疾病。为了探索左氧氟沙星对斑马鱼肠道微生物的影响及由此产生的毒性作用，采用环境浓度下的左氧氟沙星（0、0.01、0.1、1、10、100 mg·L⁻¹）浸泡成年斑马鱼10 d，然后采用石蜡切片与HE染色、16S rDNA高通量测序等方法分析斑马鱼肠道组织形态，以及肠道菌群组成的变化。结果表明，斑马鱼肠道组织切片显示肠腺体结构紊乱、黏膜层糜烂，绒毛脱落，炎症细胞数量增多，随着左氧氟沙星浓度的升高，损伤作用越强。16S rDNA高通量测序显示斑马鱼肠道细菌中放线菌门（Actinomycetota）、厚壁菌门（Firmicutes）、拟杆菌门（Bacteroidota）、变形菌门（Proteobacteria）丰度下降至对照组的70%，微生物多样性指数相较于对照组有明显下降。综上，左氧氟沙星会对斑马鱼造成显著的肠道损伤，导致肠道菌群丰度和多样性下降，进而使其免疫和代谢功能弱化。该研究为深入了解左氧氟沙星引起的肠道毒性相关机制提供了线索，并将为左氧氟沙星的合理使用提供理论参考。

关键词: 左氧氟沙星, 斑马鱼, 肠道菌群, 肠道稳态, 环境毒理, 抗生素

CLC Number:

X171.5

ZHANG Yaping, MO Cuiling, LI Yingpeng, XU Ke. Effects of Levofloxacin Exposure on Intestinal Microbes of Zebrafish[J]. Ecology and Environment, 2025, 34(4): 593-607.

张亚平, 莫璀玲, 李迎鹏, 徐棵. 左氧氟沙星暴露对斑马鱼肠道微生物的影响[J]. 生态环境学报, 2025, 34(4): 593-607.

Figures/Tables 10

Figure 1 Effects of levofloxacin exposure on Intestinal microstructure in zebrafish

Figure 2 Upset diagram of OTUs

Figure 3 Stacked diagrams of phylum and bacterial species distribution

Figure 4 Species abundance heatmap at the genus and species levels

Figure 5 Alpha diversity index of zebrafish gut microbiota

Figure 6 OTU clustering analysis

Figure 7 PCoA analysis

Figure 8 LDA and multi-level species differentiation table for different groups of gut microbiota based on LEFSe analysis

Figure 9 Channel Level2 functional abundance heatmap

Figure 10 Kruskal-Wallis rank sum test

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Effects of Levofloxacin Exposure on Intestinal Microbes of Zebrafish

左氧氟沙星暴露对斑马鱼肠道微生物的影响

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