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抗生素诱导的肠道微生物失调损害了小鼠肠道-肝脏轴的基因表达。

Antibiotic-Induced Dysbiosis of the Gut Microbiota Impairs Gene Expression in Gut-Liver Axis of Mice.

机构信息

Chongqing Key Laboratory of Big Data for Bio Intelligence, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.

出版信息

Genes (Basel). 2023 Jul 10;14(7):1423. doi: 10.3390/genes14071423.

Abstract

Antibiotics can be a double-edged sword. The application of broad-spectrum antibiotics leads to the suppression of microorganisms in the human body without selective targeting, including numerous non-pathogenic microorganisms within the gut. As a result, dysbiosis of the gut microbiota can occur. The gut microbiota is a vast and intricate ecosystem that has been connected with various illnesses. Significantly, the gut and liver function in a closely coupled anatomical and physiological relationship referred to as the "gut-liver axis". Consequently, metabolites stemming from the gut microbiota migrate via the portal vein to the liver, thereby influencing gene expression and proper physiological activity within the liver. This study aimed to investigate the dysbiosis of gut microbiota ecology and the disruption of gene expression resulting from oral antibiotics and their subsequent recovery. In the experiment, mice were tube-fed neomycin (0.5 mg/mL) and ampicillin (1 mg/mL) for 21 days (ABX group) to conduct 16s rRNA sequencing. By simultaneously analyzing public datasets PRJDB6615, which utilized the same antibiotics, it was found that nearly 50% of the total microbiota abundance was attributed to the f__Lactobacillaceae family. Additionally, datasets GSE154465 and GSE159761, using the same antibiotics, were used to screen for differentially expressed genes pre-and post-antibiotic treatment. Quantitative real-time PCR was employed to evaluate gene expression levels before and after antibiotic treatment. It was discovered that oral antibiotics significantly disrupted gene expression in the gut and liver, likely due to the dysregulation of the gut microbiota ecology. Fecal microbiota transplantation (FMT) was found to be an effective method for restoring gut microbiota dysbiosis. To further enhance the restoration of gut microbiota and gene expression, an antioxidant, vitamin C, was added to the FMT process to counteract the oxidative effect of antibiotics on microorganisms. The results showed that FMTs with vitamin C were more effective in restoring gut microbiota and gene expression to the level of the fecal transplant donor.

摘要

抗生素可能是一把双刃剑。广谱抗生素的应用会导致人体微生物群受到抑制,而没有选择性靶向,包括肠道内的许多非致病性微生物。因此,肠道微生物群落可能会出现失调。肠道微生物群落是一个庞大而复杂的生态系统,与各种疾病有关。重要的是,肠道和肝脏在解剖和生理上紧密耦合,形成了所谓的“肠-肝轴”。因此,来自肠道微生物群落的代谢物通过门静脉迁移到肝脏,从而影响肝脏内的基因表达和正常生理活动。本研究旨在研究口服抗生素引起的肠道微生物群落生态失调和基因表达紊乱及其随后的恢复。在实验中,通过管饲法给小鼠喂食新霉素(0.5mg/mL)和氨苄西林(1mg/mL)21 天(ABX 组),进行 16s rRNA 测序。通过同时分析使用相同抗生素的公共数据集 PRJDB6615,发现近 50%的总微生物群落丰度归因于 f__乳杆菌科家族。此外,使用相同抗生素的数据集 GSE154465 和 GSE159761 被用于筛选抗生素治疗前后的差异表达基因。采用定量实时 PCR 评估抗生素治疗前后的基因表达水平。结果发现,口服抗生素显著破坏了肠道和肝脏的基因表达,可能是由于肠道微生物群落生态失调所致。粪便微生物移植(FMT)被发现是一种恢复肠道微生物群落失调的有效方法。为了进一步增强肠道微生物群落和基因表达的恢复,在 FMT 过程中添加抗氧化剂维生素 C 以抵消抗生素对微生物的氧化作用。结果表明,添加维生素 C 的 FMT 更有效地将肠道微生物群落和基因表达恢复到粪便移植供体的水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cd0/10379678/b7eea7282523/genes-14-01423-g001.jpg

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