小柯机器人

德国欧洲分子生物学实验室Athanasios Typas、Lisa Maier等研究人员合作揭示抗生素对肠道细菌的附带伤害。相关论文于2021年10月13日在线发表于国际学术期刊《自然》。

研究人员表征了144种抗生素（来自于1000多种药物筛选）对38种有代表性的人类肠道微生物组物种的影响。各类抗生素表现出不同的抑制谱，包括喹诺酮类的世代依赖性和β-内酰胺类的系统发育非依赖性。大环内酯类和四环素类，这两种典型的抑菌性蛋白合成抑制剂，几乎抑制了所有测试的共生菌，但也杀死了几个物种。被杀死的细菌比被抑制的细菌更容易从体外群体中消除。这种特定物种的杀伤力挑战了长期以来杀菌和抑菌抗生素类别之间的区别，并为大环内酯类药物对动物和人类肠道微生物群的强烈影响提供了可能的解释。

为了减轻大环内酯类药物和四环素类药物的这种附带损害，研究人员筛选了一些专门拮抗抗生素活性的药物，用于保护丰富的拟杆菌属物种，但不保护相关病原体。这种解毒剂可以选择性地保护拟杆菌属物种在人类粪便菌群和无菌小鼠中的治疗。这些发现阐明了抗生素在共生细菌中的活性谱，并提出了规避其对肠道微生物群不利影响的策略。

据介绍，抗生素被用来对抗病原体，但也针对共生细菌，扰乱了肠道微生物群的组成，导致菌群失调和疾病。尽管有这种众所周知的附带损害，但不同类别的抗生素对肠道细菌的活性谱仍然没有得到很好的描述。

附：英文原文

Title: Unravelling the collateral damage of antibiotics on gut bacteria

Author: Maier, Lisa, Goemans, Camille V., Wirbel, Jakob, Kuhn, Michael, Eberl, Claudia, Pruteanu, Mihaela, Mller, Patrick, Garcia-Santamarina, Sarela, Cacace, Elisabetta, Zhang, Boyao, Gekeler, Cordula, Banerjee, Tisya, Anderson, Exene Erin, Milanese, Alessio, Lber, Ulrike, Forslund, Sofia K., Patil, Kiran Raosaheb, Zimmermann, Michael, Stecher, Brbel, Zeller, Georg, Bork, Peer, Typas, Athanasios

Issue&Volume: 2021-10-13

Abstract: Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease1. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species2. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for β-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal3,4,5 and human6,7 gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.

DOI: 10.1038/s41586-021-03986-2

Source: https://www.nature.com/articles/s41586-021-03986-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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