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在全身感染模型中,美罗培南治疗后肠道微生物群未恢复。

Absence of gut microbiota restoration following meropenem treatment in a systemic infection model.

作者信息

Ribeiro Filipe Moura, Ribeiro Camila Fontoura Acosta, de Souza Cândido Elizabete, Buccini Danieli Fernanda, Cardoso Marlon Henrique, Greice de Oliveira Silva Silveira Gislaine, de Souza Carolina Moura, Silva Osmar Nascimento, de Andrade Gisele Braziliano, da Silva Alanderson Rodrigues, da Mota Franciele Bathel, Makimoto Sarah Saory, Dos Santos Ferreira Rosangela, de Oliveira Nathália Cavichiolli, de Castro Alinne Pereira, Carvalho Cristiano Marcelo Espínola, de la Fuente-Nunez Cesar, Franco Octávio Luiz

机构信息

Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil.

Laboratory of Molecular Exercise Physiology - University Center - UDF, Brasilia, DF, Brazil.

出版信息

NPJ Antimicrob Resist. 2025 Jun 30;3(1):60. doi: 10.1038/s44259-025-00129-9.

Abstract

Antibiotics have been shown to have unintended effects on the host by disrupting the beneficial microbiota. In this study, we explored and longitudinally monitored microbiota during and after antibiotic treatment for infection. We induced a systemic Escherichia coli infection in 45 BALB/c mice, with 25 as uninfected controls. The disease was treated with meropenem. The animals were evaluated longitudinally three times, including 3 hours, five days of treatment, and 30 days post-treatment. Intestinal, lung, blood, and peritoneal lavage samples were collected for analysis. Our findings show that meropenem effectively treated the lethal systemic infection caused by E. coli. Hematological parameters, crypt depth, and goblet cell numbers remained unchanged for 30 days post-antibiotic treatment. However, antibiotic treatment impaired the recovery of the gut microbiota, even 30 days post-treatment. This long-term meropenem impact on microbiota was observed in both infected and non-infected (saline-treated) groups. Alpha and beta diversity analyses did not indicate a microbiota recovery. Notably, Lactobacillus and Bacteroides decreased, while Clostridioides, Enterococcus, and Escherichia-Shigella increased. This study provides novel evidence that, even 30 days after meropenem treatment in a simulated E. coli infection, the intestinal microbiota does not recover, highlighting prolonged antibiotic-induced dysbiosis.

摘要

抗生素已被证明会通过破坏有益微生物群对宿主产生意想不到的影响。在本研究中,我们对抗生素治疗感染期间及之后的微生物群进行了探索和纵向监测。我们在45只BALB/c小鼠中诱导了全身性大肠杆菌感染,25只作为未感染对照。用美罗培南治疗该疾病。对动物进行了三次纵向评估,包括治疗后3小时、治疗5天和治疗后30天。收集肠道、肺、血液和腹腔灌洗样本进行分析。我们的研究结果表明,美罗培南有效地治疗了由大肠杆菌引起的致命性全身感染。抗生素治疗后30天,血液学参数、隐窝深度和杯状细胞数量保持不变。然而,即使在治疗后30天,抗生素治疗仍损害了肠道微生物群的恢复。在感染组和未感染(生理盐水处理)组中均观察到美罗培南对微生物群的这种长期影响。α和β多样性分析未表明微生物群恢复。值得注意的是,乳酸杆菌和拟杆菌减少,而梭状芽孢杆菌、肠球菌和埃希氏菌-志贺氏菌增加。这项研究提供了新的证据,即在模拟大肠杆菌感染中使用美罗培南治疗30天后,肠道微生物群仍未恢复,突出了抗生素诱导的长期生态失调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e29/12209465/e4e607bedb34/44259_2025_129_Fig1_HTML.jpg

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