生命早期肠道抵抗组和活动组的动态:一项荟萃分析。

IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Ahmed Bargheet, Hanna Theodora Noordzij, Alise J Ponsero, Ching Jian, Katri Korpela, Mireia Valles-Colomer, Justine Debelius, Alexander Kurilshikov, Veronika Kuchařová Pettersen
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引用次数: 0

摘要

背景:与成人相比,婴儿肠道菌群中抗生素耐药基因(ARGs)的比例更高,即使在从未接触过抗生素的婴儿中也是如此。我们的研究旨在通过分析不同的围产期因素如何影响婴儿肠道中ARGs、移动遗传元件(MGEs)及其细菌宿主的存在来阐明这一现象。方法:我们检索了MEDLINE和Embase,检索了截至2023年4月3日的报告婴儿队列粪便样本霰弹枪宏基因组测序的研究。系统搜索确定了来自三大洲10个国家的14个纵向婴儿队列,具有公开可用的测序数据和相应的元数据。为了进行后续的综合生物信息学分析,我们使用了来自1270名婴儿和415名母亲的3981个高质量宏基因组样本。研究结果:我们确定了与出生方式、胎龄、抗生素使用和地理位置相关的抵抗组和移动组的明显轨迹。来自欧洲、南部非洲和北美的队列之间的差异体现了地理差异,这表明arg的多样性和丰度都存在差异。另一方面,我们没有发现母乳喂养对婴儿肠道抵抗组有显著影响。在大肠杆菌和粪肠球菌等关键细菌宿主中,半数以上检测到的ARGs与质粒共定位。这些arg相关的质粒在婴儿期逐渐丢失。我们还证明,与成人相比,大肠杆菌作为婴儿肠道抵抗组和移动组的主要调节剂,其丰度和菌株多样性的增加促进了大肠杆菌的作用。解释:出生方式、胎龄、抗生素暴露和地理位置显著影响婴儿肠道抵抗组和移动组的发育。随着时间的推移,大肠杆菌相对丰度的减少似乎是导致婴儿生长过程中抵抗组和质粒相对丰度下降的关键因素。资助:挪威奥斯陆高级研究中心。通过挪威特罗姆瑟研究基金会资助的新型抗菌策略中心。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dynamics of gut resistome and mobilome in early life: a meta-analysis.

Background: The gut microbiota of infants harbours a higher proportion of antibiotic resistance genes (ARGs) compared to adults, even in infants never exposed to antibiotics. Our study aims to elucidate this phenomenon by analysing how different perinatal factors influence the presence of ARGs, mobile genetic elements (MGEs), and their bacterial hosts in the infant gut.

Methods: We searched MEDLINE and Embase up to April 3rd, 2023, for studies reporting infant cohorts with shotgun metagenomic sequencing of stool samples. The systematic search identified 14 longitudinal infant cohorts from 10 countries across three continents, featuring publicly available sequencing data with corresponding metadata. For subsequent integrative bioinformatic analyses, we used 3981 high-quality metagenomic samples from 1270 infants and 415 mothers.

Findings: We identified distinct trajectories of the resistome and mobilome associated with birth mode, gestational age, antibiotic use, and geographical location. Geographical variation was exemplified by differences between cohorts from Europe, Southern Africa, and Northern America, which showed variation in both diversity and abundance of ARGs. On the other hand, we did not detect a significant impact of breastfeeding on the infants' gut resistome. More than half of detected ARGs co-localised with plasmids in key bacterial hosts, such as Escherichia coli and Enterococcus faecalis. These ARG-associated plasmids were gradually lost during infancy. We also demonstrate that E. coli role as a primary modulator of the infant gut resistome and mobilome is facilitated by its increased abundance and strain diversity compared to adults.

Interpretation: Birth mode, gestational age, antibiotic exposure, and geographical location significantly influence the development of the infant gut resistome and mobilome. A reduction in E. coli relative abundance over time appears as a key factor driving the decrease in both resistome and plasmid relative abundance as infants grow.

Funding: Centre for Advanced Study in Oslo, Norway. Centre for New Antibacterial Strategies through the Tromsø Research Foundation, Norway.

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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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