Yin Jia, M Prabhakar, Wang Shan, Liao Shuo-Xi, Peng Xin, He Yan, Chen Yi-Ran, Shen Hua-Fang, Su Jin, Chen Ye, Jiang Yun-Xia, Zhang Guo-Xia, Zhou Hong-Wei
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China 510515.
State Key Laboratory of Organ Failure Research, Department of Environmental Health, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China 510515.
PLoS One. 2015 May 13;10(5):e0126712. doi: 10.1371/journal.pone.0126712. eCollection 2015.
The adverse impact of antibiotics on the gut microbiota has attracted extensive interest, particularly due to the development of microbiome research techniques in recent years. However, a direct comparison of the dynamic effects of various types of antibiotics using the same animal model has not been available. In the present study, we selected six antibiotics from four categories with the broadest clinical usage, namely, β-lactams (Ceftriaxone Sodium, Cefoperazone/Sulbactam and meropenem), quinolones (ofloxacin), glycopeptides (vancomycin), and macrolides (azithromycin), to treat BALB/c mice. Stool samples were collected during and after the administration of antibiotics, and microbial diversity was analyzed through Illumina sequencing and bioinformatics analyses using QIIME. Both α and β diversity analyses showed that ceftriaxone sodium, cefoperazone/sulbactam, meropenem and vancomycin changed the gut microbiota dramatically by the second day of antibiotic administration whereas the influence of ofloxacin was trivial. Azithromycin clearly changed the gut microbiota but much less than vancomycin and the β-lactams. In general, the community changes induced by the three β-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium. The low diversity and high Clostridium level might be an important cause of Clostridium difficile infection after usage of β-lactams. Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium. On the other hand, it induced the growth of Escherichia and effect lasted for months afterward. Azithromycin and meropenem induced the growth of Enterococcus. These findings will be useful for understanding the potential adverse effects of antibiotics on the gut microbiome and ensuring their better usage.
抗生素对肠道微生物群的不利影响引起了广泛关注,特别是由于近年来微生物组研究技术的发展。然而,尚未有使用相同动物模型对各类抗生素的动态效应进行直接比较的研究。在本研究中,我们从临床应用最广泛的四类抗生素中选取了六种,即β-内酰胺类(头孢曲松钠、头孢哌酮/舒巴坦和美罗培南)、喹诺酮类(氧氟沙星)、糖肽类(万古霉素)和大环内酯类(阿奇霉素),用于治疗BALB/c小鼠。在抗生素给药期间及之后收集粪便样本,并通过Illumina测序和使用QIIME的生物信息学分析来分析微生物多样性。α多样性和β多样性分析均表明,头孢曲松钠、头孢哌酮/舒巴坦、美罗培南和万古霉素在抗生素给药第二天就显著改变了肠道微生物群,而氧氟沙星的影响微不足道。阿奇霉素明显改变了肠道微生物群,但程度远低于万古霉素和β-内酰胺类抗生素。总体而言,三种β-内酰胺类抗生素引起的群落变化在抑制乳头杆菌属、普雷沃氏菌属和艾氏菌属的同时,诱导梭菌大量生长方面表现出一致性。低多样性和高梭菌水平可能是使用β-内酰胺类抗生素后艰难梭菌感染的重要原因。万古霉素的独特之处在于它抑制厚壁菌门,主要是梭菌属。另一方面,它诱导大肠杆菌生长,且这种影响持续数月。阿奇霉素和美罗培南诱导肠球菌生长。这些发现将有助于理解抗生素对肠道微生物组的潜在不利影响,并确保其更好的使用。