摘要
      水生环境中的卡马西平（CBZ）被认为是对水生生物和公众健康的潜在威胁。然而，CBZ暴露后生物体肠道健康、耐药性、微生物群的反应及其关系很少报道。本研究旨在利用斑马鱼模型探讨CBZ对肠道微生物群、抗生素耐药性基因（ARGs）和肠道健康相关基因表达的影响及其相互作用。16S核糖体RNA测序表明CBZ改变了肠道微生物群的组成。使用高通量定量聚合酶链式反应（HT-qPCR），我们发现ARGs的数量和丰度受到CBZ水平和暴露时间的影响。我们还观察到，在不同暴露时间，促炎基因IL6的表达上调，toll样受体基因TLR2和肠屏障基因TJP2a的表达下调。相关分析表明，地杆菌属、红球菌属、雷氏菌属、德尔夫蒂亚属、木犀杆菌属和志贺氏大肠杆菌属可能是携带ARGs的主要细菌属。同时，Cetobacterium和Aeromonas可能是影响肠道健康相关基因的优势细菌。我们的研究结果有助于了解CBZ对水生动物肠道微生态的健康风险。
Abstract
Carbamazepine (CBZ) in the aquatic environment is recognized as a potential threat to aquatic organisms and public health. However, the response of organism intestinal health, resistome, microbiota, and their relationship after CBZ exposure has been rarely reported. This study aimed to explore the impacts of CBZ on gut microbiota, antibiotic resistance genes (ARGs) and the expression of intestinal health related genes as well as their interaction using the zebrafish model. 16 S ribosomal RNA sequencing indicated CBZ altered the composition of gut microbiota. Using high-throughput quantitative polymerase chain reaction (HT-qPCR), we found the number and abundance of ARGs were impacted by CBZ levels and exposure duration. We also observed the upregulated expression of the pro-inflammatory gene IL6 and downregulated expression of toll-like receptor gene TLR2 and intestinal barrier gene TJP2a at different exposure times. Correlation analyses revealed that Geobacillus, Rhodococcus, Ralstonia, Delftia, Luteolibacter and Escherichia-Shigella might be the main bacterial genera carrying ARGs. Meanwhile, Cetobacterium and Aeromonas could be the dominant bacteria affecting intestinal health related genes. Our results could contribute to understanding the health risks of CBZ to the intestinal microecology of aquatic animals.

https://www.sciencedirect.com/science/article/pii/S0147651322013136