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不同阿莫西林治疗时长对肠道微生物多样性和组成的影响。

Effects of different amoxicillin treatment durations on microbiome diversity and composition in the gut.

机构信息

Department of Pharmacy, Section for Pharmacology and Pharmaceutical Biosciences, University of Oslo, Oslo, Norway.

Faculty of Dentistry, Institute of Oral Biology, University of Oslo, Oslo, Norway.

出版信息

PLoS One. 2022 Oct 27;17(10):e0275737. doi: 10.1371/journal.pone.0275737. eCollection 2022.

Abstract

Antibiotics seize an effect on bacterial composition and diversity and have been demonstrated to induce disruptions on gut microbiomes. This may have implications for human health and wellbeing, and an increasing number of studies suggest a link between the gut microbiome and several diseases. Hence, reducing antibiotic treatments may be beneficial for human health status. Further, antimicrobial resistance (AMR) is an increasing global problem that can be counteracted by limiting the usage of antibiotics. Longer antibiotic treatments have been demonstrated to increase the development of AMR. Therefore, shortening of antibiotic treatment durations, provided it is safe for patients, may be one measure to reduce AMR. In this study, the objective was to investigate effects of standard and reduced antibiotic treatment lengths on gut microbiomes using a murine model. Changes in the murine gut microbiome was assessed after using three different treatment durations of amoxicillin (3, 7 or 14 days) as well as a control group not receiving amoxicillin. Fecal samples were collected before and during the whole experiment, until three weeks past end of treatment. These were further subject for 16S rRNA Illumina MiSeq sequencing. Our results demonstrated significant changes in bacterial diversity, richness and evenness during amoxicillin treatment, followed by a reversion in terms of alpha-diversity and abundance of major phyla, after end of treatment. However, a longer restitution time was indicated for mice receiving amoxicillin for 14 days, and phylum Patescibacteria did not fully recover. In addition, an effect on the composition of Firmicutes was indicated to last for at least three weeks in mice treated with amoxicillin for 14 days. Despite an apparently reversion to a close to original state in overall bacterial diversity and richness, the results suggested more durable changes in lower taxonomical levels. We detected several families, genera and ASVs with significantly altered abundance three weeks after exposure to amoxicillin, as well as bacterial taxa that appeared significantly affected by amoxicillin treatment length. This may strengthen the argument for shorter antibiotic treatment regimens to both limit the emergence of antibiotic resistance and risk of gut microbiome disturbance.

摘要

抗生素对细菌组成和多样性有影响,并已被证明会破坏肠道微生物组。这可能对人类健康和福祉产生影响,越来越多的研究表明肠道微生物组与多种疾病之间存在关联。因此,减少抗生素治疗可能有益于人类健康状况。此外,抗菌药物耐药性(AMR)是一个日益严重的全球性问题,可以通过限制抗生素的使用来对抗。已证明较长的抗生素治疗会增加 AMR 的发展。因此,缩短抗生素治疗时间(只要对患者安全)可能是减少 AMR 的一项措施。在这项研究中,我们的目的是使用小鼠模型研究标准和缩短的抗生素治疗时间对肠道微生物组的影响。在使用阿莫西林(3、7 或 14 天)三种不同治疗时间以及未接受阿莫西林的对照组后,评估了小鼠肠道微生物组的变化。在整个实验过程中收集粪便样本,直到治疗结束后三周。进一步对这些样本进行 16S rRNA Illumina MiSeq 测序。我们的结果表明,在阿莫西林治疗期间,细菌多样性、丰富度和均匀度发生了显著变化,治疗结束后,α多样性和主要门的丰度恢复。然而,接受 14 天阿莫西林治疗的小鼠需要更长的恢复时间,而 Patescibacteria 门未完全恢复。此外,在接受 14 天阿莫西林治疗的小鼠中,Firmicutes 门的组成受到影响,至少持续了 3 周。尽管细菌多样性和丰富度总体上似乎恢复到接近原始状态,但结果表明较低分类水平的变化更为持久。我们检测到在接触阿莫西林后 3 周时,有几个家族、属和 ASVs 的丰度发生了显著变化,以及受阿莫西林治疗时间影响的细菌分类群。这可能加强了采用较短抗生素治疗方案的论点,以限制抗生素耐药性的出现和肠道微生物组紊乱的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0007/9612567/5e4e60a5ca5b/pone.0275737.g001.jpg

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