Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria
Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria
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DOI：
10.1186/s13756-019-0583-6
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发表时间：
2019-08-14
影响因子：
5.5
通讯作者：
Underwood, Mark A.
中科院分区：
文献类型：
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作者：
Casaburi, Giorgio;Duar, Rebbeca M.;Underwood, Mark A.
背景抗生素耐药（AR）细菌是一个全球性的威胁。AR细菌可以在生命早期获得，并有长期后遗症。限制抗生素耐药性的传播而不引发其他耐药机制的发展具有巨大的临床价值。在这里，我们展示了如何修改婴儿肠道微生物组，从而显著减少AR基因（ARG）和携带它们的潜在致病细菌。方法使用鸟枪宏基因组学对来自两组健康足月母乳喂养婴儿的粪便样本进行肠道微生物组学表征。一组喂饲B。EVC 001组（n = 29，EVC 001喂养组）除接受泌乳支持外，另一组（n = 31，对照组）仅接受泌乳支持。从粪便样品中分离大肠菌群并进行基因组测序，以及测试对临床相关抗生素的最小抑菌浓度。结果婴儿喂养B. EVC 001的肠道微生物组发生了变化，导致ARG水平比对照组低90%。预测组间差异显著的ARG会对β内酰胺类、氟喹诺酮类或多种药物类别产生耐药性，其中大多数属于埃希氏菌、梭菌和葡萄球菌。最小抑菌浓度测定证实了这些基因的菌株之间的耐药表型。值得注意的是，我们在从未接触过抗生素的健康、经阴道分娩的母乳喂养婴儿中发现了超广谱β内酰胺酶。结论单一菌株B在母乳喂养婴儿肠道定植。长双歧杆菌婴儿亚种粪便对粪便宏基因组产生了深远的影响，包括减少ARG。这突出了开发新方法以限制这些基因在临床相关细菌中传播的重要性。未来的研究需要确定是否定植与B。EVC 001可降低母乳喂养婴儿AR感染的发生率。
Background Antibiotic-resistant (AR) bacteria are a global threat. AR bacteria can be acquired in early life and have long-term sequelae. Limiting the spread of antibiotic resistance without triggering the development of additional resistance mechanisms is of immense clinical value. Here, we show how the infant gut microbiome can be modified, resulting in a significant reduction of AR genes (ARGs) and the potentially pathogenic bacteria that harbor them. Methods The gut microbiome was characterized using shotgun metagenomics of fecal samples from two groups of healthy, term breastfed infants. One group was fed B. infantis EVC001 in addition to receiving lactation support (n = 29, EVC001-fed), while the other received lactation support alone (n = 31, controls). Coliforms were isolated from fecal samples and genome sequenced, as well as tested for minimal inhibitory concentrations against clinically relevant antibiotics. Results Infants fed B. infantis EVC001 exhibited a change to the gut microbiome, resulting in a 90% lower level of ARGs compared to controls. ARGs that differed significantly between groups were predicted to confer resistance to beta lactams, fluoroquinolones, or multiple drug classes, the majority of which belonged to Escherichia, Clostridium, and Staphylococcus. Minimal inhibitory concentration assays confirmed the resistance phenotypes among isolates with these genes. Notably, we found extended-spectrum beta lactamases among healthy, vaginally delivered breastfed infants who had never been exposed to antibiotics. Conclusions Colonization of the gut of breastfed infants by a single strain of B. longum subsp. infantis had a profound impact on the fecal metagenome, including a reduction in ARGs. This highlights the importance of developing novel approaches to limit the spread of these genes among clinically relevant bacteria. Future studies are needed to determine whether colonization with B. infantis EVC001 decreases the incidence of AR infections in breastfed infants.