摘要

在过去的几十年中，通过在农业和人类医学中大规模使用抗生素来污染环境导致环境和宿主动物微生物组中的抗微生物抗性增加。宿主微生物组的紊乱可导致免疫力下降和水产养殖物种的恢复力降低。在这里，我们调查了环境测量的常用抗生素环丙沙星和土霉素的水平是否影响宿主微生物组和幼虫斑马鱼中皂苷诱导的免疫刺激的易感性。首先，通过浸泡将中性粒细胞和巨噬细胞报告基因斑马鱼幼虫暴露于不同浓度的大豆皂苷。观察到肠区中嗜中性粒细胞存在的剂量依赖性增加以及免疫基因il1b，tnfa，il22和mmp9的表达增加。为了研究抗生素的作用，在存在或不存在低剂量的皂苷的情况下将幼虫斑马鱼浸入环丙沙星或土霉素中。体内成像显示抗生素治疗并未减少皂苷暴露后募集到肠道区域的中性粒细胞的数量，尽管它确实倾向于降低促炎细胞因子水平。整个幼虫的微生物测序表明，暴露于低剂量的皂苷已经改变了微生物组成。与对照相比，土霉素和皂苷的组合显着增加了α-多样性。总之，目前的研究提供的证据表明，低水平的抗生素与低水平的抗营养因子（皂苷）的组合可以诱导炎症表型并且可以改变微生物群，这可能导致疾病易感性的改变。

In the last decades, pollution of the environment by large scale use of antibiotics in agriculture and human medicine have led to increased antimicrobial resistance in both the environment and the host animal microbiome. Disturbances in the host microbiome can result in impaired immunity and reduced resilience of aquaculture species. Here, we investigated whether environmentally measured levels of the commonly used antibiotics ciprofloxacin and oxytetracycline influences the host microbiome and susceptibility toward saponin-induced immune stimulation in larval zebrafish. Firstly, neutrophil and macrophage reporter zebrafish larvae were exposed to different concentrations of soy saponin by immersion. A dose-dependent increase in neutrophil presence in the intestinal area was observed together with increased expression of immune genes il1b, tnfa, il22 and mmp9. To investigate the effect of antibiotics, larval zebrafish were immersed in ciprofloxacin or oxytetracycline in the presence or absence of a low dose of saponin. In vivo imaging revealed that antibiotic treatment did not reduce the number of neutrophils that were recruited to the intestinal area upon saponin exposure, although it did tend to lower pro-inflammatory cytokine levels. Microbial sequencing of whole larvae revealed that exposure to a low dose of saponin already shifted the microbial composition. The combination of oxytetracycline and saponin significantly increased α-diversity compared to the controls. In conclusion, the current study provides evidence that the combination of low levels of antibiotics with low levels of anti-nutritional factors (saponin) can induce inflammatory phenotypes and can modify the microbiota, which might lead to altered disease susceptibility.

https://www.ncbi.nlm.nih.gov/pubmed/30420850