Non-responder phenotype reveals apparent microbiome-wide antibiotic tolerance in the murine gut.
Non-responder phenotype reveals apparent microbiome-wide antibiotic tolerance in the murine gut.
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DOI：
10.1038/s42003-021-01841-8
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发表时间：
2021-03-09
影响因子：
5.9
通讯作者：
Gibbons SM
中科院分区：
文献类型：
--
作者：
Diener C;Hoge ACH;Kearney SM;Kusebauch U;Patwardhan S;Moritz RL;Erdman SE;Gibbons SM
广谱抗生素对肠道微生物组的生态造成短暂和持久的损害。抗生素诱导的肠道细菌多样性丧失与肠道感染的易感性有关。先前在人类和非人类动物中进行的亚治疗性抗生素治疗的工作表明，整个肠道群落可能表现出耐受性表型。在这项研究中，我们验证了这些社区耐受性表型在小鼠肠道中的存在，并探讨抗生素治疗时间或富含抗菌植物化学物质的饮食如何影响这种表型的频率。几乎三分之一的小鼠表现出对高剂量β-内酰胺类抗生素头孢哌酮的整体耐受性，与抗生素治疗持续时间或饮食植物化学修正无关。我们观察到抗生素治疗期间的非应答微生物群与未治疗的对照微生物群之间的组成差异很少。然而，在治疗期间，非应答者微生物群和对照组之间的基因表达存在巨大差异，非应答者群体显示出抗菌素耐受性基因（如外排转运蛋白）的上调和中枢代谢的下调。未来的工作应该集中在哪些特定的宿主或微生物相关因素负责在应答者和非应答者表型之间倾斜社区，以便我们可以学会利用这种现象来保护我们的微生物群免受常规抗生素治疗。Diener、Hoge等人表明，三分之一的小鼠表现出对高剂量β-内酰胺抗生素头孢哌酮的耐受性，与抗生素治疗持续时间或饮食植物化学物质的修正无关。他们发现，非应答菌群上调抗菌素耐受性基因并下调中枢代谢，而不改变群落组成或多样性，从而深入了解整个社区的抗生素耐受性机制。
Broad spectrum antibiotics cause both transient and lasting damage to the ecology of the gut microbiome. Antibiotic-induced loss of gut bacterial diversity has been linked to susceptibility to enteric infections. Prior work on subtherapeutic antibiotic treatment in humans and non-human animals has suggested that entire gut communities may exhibit tolerance phenotypes. In this study, we validate the existence of these community tolerance phenotypes in the murine gut and explore how antibiotic treatment duration or a diet enriched in antimicrobial phytochemicals might influence the frequency of this phenotype. Almost a third of mice exhibited whole-community tolerance to a high dose of the β-lactam antibiotic cefoperazone, independent of antibiotic treatment duration or dietary phytochemical amendment. We observed few compositional differences between non-responder microbiota during antibiotic treatment and the untreated control microbiota. However, gene expression was vastly different between non-responder microbiota and controls during treatment, with non-responder communities showing an upregulation of antimicrobial tolerance genes, like efflux transporters, and a down-regulation of central metabolism. Future work should focus on what specific host- or microbiome-associated factors are responsible for tipping communities between responder and non-responder phenotypes so that we might learn to harness this phenomenon to protect our microbiota from routine antibiotic treatment. Diener, Hoge et al. show that a third of mice exhibit tolerance to a high dose of the β-lactam antibiotic cefoperazone, independent of antibiotic treatment duration or dietary phytochemical amendment. They find that non-responder microbiota upregulates antimicrobial tolerance genes and downregulates central metabolism without altering community composition or diversity, providing insights into the mechanisms of community-wide antibiotic tolerance.
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影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
DOI：
10.1016/j.ijantimicag.2003.05.018
发表时间：
2004-01-01
影响因子：
10.8
作者：
Hanaki, H;Yamaguchi, Y;Sunakawa, K
通讯作者：
Sunakawa, K
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.6
作者：
Dardas, Majd;Gill, Steven R.;Guillet, Ronnie
通讯作者：
Guillet, Ronnie