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一种基于人类微生物组模型的抗肿瘤治疗中依赖微生物组的反应:羟基脲和柔红霉素的初步研究

A Microbiota-Dependent Response to Anticancer Treatment in an Human Microbiota Model: A Pilot Study With Hydroxycarbamide and Daunorubicin.

机构信息

IAME, UMR 1137, INSERM, Université de Paris, AP-HP, Paris, France.

INSERM U1016, team "Mucosal microbiota in chronic inflammatory diseases", CNRS UMR 8104, Université de Paris, Paris, France.

出版信息

Front Cell Infect Microbiol. 2022 Jun 1;12:886447. doi: 10.3389/fcimb.2022.886447. eCollection 2022.

Abstract

BACKGROUND

Anticancer drug efficacy is linked to the gut microbiota's composition, and there is a dire need to better understand these interactions for personalized medicine. microbiota models are promising tools for studies requiring controlled and repeatable conditions. We evaluated the impact of two anticancer drugs on human feces in the MiniBioReactor Array (MBRA) microbiota system.

METHODS

The MBRA is a single-stage continuous-flow culture model, hosted in an anaerobic chamber. We evaluated the effect of a 5-day treatment with hydroxycarbamide or daunorubicine on the fecal bacterial communities of two healthy donors. 16S microbiome profiling allowed analysis of microbial richness, diversity, and taxonomic changes.

RESULTS

In this host-free setting, anticancer drugs diversely affect gut microbiota composition. Daunorubicin was associated with significant changes in alpha- and beta-diversity as well as in the ratio of Firmicutes/Bacteroidetes in a donor-dependent manner. The impact of hydroxycarbamide on microbiota composition was not significant.

CONCLUSION

We demonstrated, for the first time, the impact of anticancer drugs on human microbiota composition, in a donor- and molecule-dependent manner in an human microbiota model. We confirm the importance of personalized studies to better predict drug-associated-dysbiosis , linked to the host's response to treatment.

摘要

背景

抗癌药物的疗效与肠道微生物群的组成有关,因此迫切需要更好地了解这些相互作用,以实现个性化医疗。微生物群模型是研究需要控制和可重复条件的有前途的工具。我们评估了两种抗癌药物在 MiniBioReactor Array (MBRA) 微生物群系统中对人粪便的影响。

方法

MBRA 是一种单级连续流动培养模型,在厌氧室中运行。我们评估了羟基脲或柔红霉素 5 天治疗对两名健康供体粪便中细菌群落的影响。16S 微生物组分析允许分析微生物丰富度、多样性和分类变化。

结果

在这种无宿主的环境中,抗癌药物对肠道微生物群组成有不同的影响。柔红霉素与 alpha 和 beta 多样性以及梭菌/拟杆菌比例的显著变化相关,且在供体依赖性方式下相关。羟基脲对微生物群组成的影响不显著。

结论

我们首次在人类微生物群模型中,以供体和分子依赖的方式,证明了抗癌药物对人类微生物群组成的影响。我们证实了个性化研究的重要性,以更好地预测与宿主对治疗的反应相关的药物相关失调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d3/9198576/4321844083c8/fcimb-12-886447-g001.jpg

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