Carlson Jeanette M, Hyde Embriette R, Petrosino Joseph F, Manage Ananda B W, Primm Todd P
Department of Biological Sciences, Sam Houston State University, Huntsville, TX, USA.
Center for Metagenomics and Microbiome Research, Integrative Molecular and Biosciences Training Program and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2015 Dec;178:163-168. doi: 10.1016/j.cbpc.2015.10.004. Epub 2015 Oct 18.
While serving as critical tools against bacterial infections, antimicrobial therapies can also result in serious side effects, such as antibiotic-associated entercolitis. Recent studies utilizing next generation sequencing to generate community 16S gene profiles have shown that antibiotics can strongly alter community composition and deplete diversity. However, how these community changes in the microbiota are related to the host side effects is still unclear. We have used the freshwater Western mosquitofish (Gambusia affinis) as a tractable vertebrate model system to study host effects following exposure to a broad spectrum antibiotic, rifampicin. After 3days of exposure, the bacterial communities of the mucosal skin and gut microbiomes lost diversity and shifted composition. Compared to unexposed controls, treated fish were more susceptible to a specific pathogen, Edwardsiella ictaluri, yet displayed no survival differences when subjected to a polymicrobial water challenge of soil or feces. Treated fish were more susceptible to osmotic stress from NaCl, but not to the toxin nitrate. Treated fish failed to gain weight as well as controls over one month when fed a matched diet. Because of small sample sizes, pathogen susceptibility and weight gain differences were not statistically significant. This study provides supporting evidence in an experimental laboratory system that an antibiotic can have significant and persistent negative host effects, and provides for future study into the mechanisms of these effects.
抗菌疗法虽然是对抗细菌感染的关键手段,但也可能导致严重的副作用,如抗生素相关性小肠结肠炎。最近利用下一代测序技术生成群落16S基因图谱的研究表明,抗生素可强烈改变群落组成并减少多样性。然而,微生物群中的这些群落变化与宿主副作用之间的关系仍不清楚。我们使用淡水西部食蚊鱼(Gambusia affinis)作为一个易于处理的脊椎动物模型系统,来研究接触广谱抗生素利福平后的宿主效应。暴露3天后,粘膜皮肤和肠道微生物群的细菌群落失去了多样性,组成也发生了变化。与未暴露的对照组相比,经处理的鱼对特定病原体鮰爱德华氏菌更易感,但在接受土壤或粪便的多微生物水挑战时,存活率没有差异。经处理的鱼对氯化钠引起的渗透胁迫更敏感,但对硝酸盐毒素不敏感。在喂食匹配饲料的情况下,经处理的鱼在一个月内体重增加不及对照组。由于样本量小,病原体易感性和体重增加差异无统计学意义。本研究在实验实验室系统中提供了支持性证据,表明抗生素可对宿主产生显著且持久的负面效应,并为今后研究这些效应的机制提供了依据。