State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang 315211, China.
Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Meishan Campus, Ningbo University, Ningbo, Zhejiang 315211, China.
Zool Res. 2022 Jul 18;43(4):648-665. doi: 10.24272/j.issn.2095-8137.2022.159.
With the rapid development of intensive farming, the aquaculture industry uses a great many antibiotics for the prevention and treatment of bacterial diseases. Despite their therapeutic functions, the overuse and accumulation of antibiotics also pose a threat to aquaculture organisms. In the present study, ayu ( ) was used as a fish model to study the impacts of ciprofloxacin (CIP) overuse on intestinal homeostasis and immune response during subsequent infection. Based on 16S rRNA gene amplification and Illumina sequencing, we found that CIP pre-exposure caused significant variation in intestinal microbiota, including increased species richness, altered microbiota composition and interaction networks, and increased metabolic dysfunction. Furthermore, immunohistochemical analysis indicated that CIP pre-exposure resulted in severe mucosal layer damage, goblet cell reduction, and epithelial cell necrosis of the intestinal barrier in infected ayu. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that disruption of intestinal homeostasis impaired systemic anti-infection immune responses in the intestine, gill, spleen, and head kidney, while inhibiting , , and expression and promoting expression. Our findings indicated that CIP administration can directly affect intestinal microbiota composition and intestinal integrity in ayu fish. This perturbation of intestinal homeostasis is likely responsible for the lower survival rate of hosts following subsequent infection as the capacity to mount an effective immune response is compromised. This study also provides preliminary clues for understanding the effects of antibiotic overuse on higher vertebrates through trophic transfer.
随着集约化养殖的快速发展，水产养殖业大量使用抗生素来预防和治疗细菌性疾病。尽管抗生素具有治疗作用，但过度使用和积累也会对水产养殖生物构成威胁。在本研究中，我们使用牙鲆（ ）作为鱼类模型，研究了环丙沙星（CIP）过度使用对随后感染期间肠道稳态和免疫反应的影响。基于 16S rRNA 基因扩增和 Illumina 测序，我们发现 CIP 预先暴露导致肠道微生物群落发生显著变化，包括物种丰富度增加、微生物群落组成和相互作用网络改变以及代谢功能障碍增加。此外，免疫组织化学分析表明，CIP 预先暴露导致感染牙鲆的肠道黏膜层严重损伤、杯状细胞减少和上皮细胞坏死。定量实时聚合酶链反应（qRT-PCR）显示，肠道稳态的破坏削弱了肠道、鳃、脾脏和头肾的全身抗感染免疫反应，同时抑制了 、 、 和 的表达，促进了 的表达。我们的研究结果表明，CIP 给药可以直接影响牙鲆肠道的微生物群落组成和肠道完整性。这种肠道稳态的破坏可能是宿主在随后感染后存活率降低的原因，因为其产生有效免疫反应的能力受到了损害。本研究还通过营养转移为理解抗生素过度使用对高等脊椎动物的影响提供了初步线索。
