摘要
出身背景
幼儿经常接触抗生素，有可能对肠道微生物组产生副作用。抗生素暴露于脱靶微生物（即未被治疗靶向的细菌）和抗生素耐药性基因（ARGs）的影响尚不清楚。
方法
我们使用了在抗生素暴露前和1岁时从200多名婴儿中收集的成对粪便样本的宏基因组测序数据，以及差异分析法来评估随后的暴露与微生物和ARGs的丰度或组成多样性之间的关系，同时调整协变量。
后果
到1年时，多个物种和ARGs的丰度因抗生素暴露而不同。与从未接触过抗生素的婴儿相比，vulgatus拟杆菌的相对丰度增加了1.72%（95%CI:0.19，3.24），而脆弱拟杆菌减少了1.56%（95%CI:−4.32，1.21）。双歧杆菌物种也表现出相反的趋势。与暴露相关的ARGs包括A类β-内酰胺酶基因CfxA6。在接受日托的婴儿中，大肠杆菌和ARG的丰度都与抗生素的使用呈正相关。
结论
通过考虑基线和干预后的微生物组数据，确定了新的发现，包括日托护理的重要性。因此，我们的研究设计和方法对未来评估抗生素意外影响的研究具有重要意义。
Abstract
Background
Young children are frequently exposed to antibiotics, with the potential for collateral consequences to the gut microbiome. The impact of antibiotic exposures to off-target microbes (i.e., bacteria not targeted by treatment) and antibiotic resistance genes (ARGs) is poorly understood.

Methods
We used metagenomic sequencing data from paired stool samples collected prior to antibiotic exposure and at 1 year from over 200 infants and a difference-in-differences approach to assess the relationship between subsequent exposures and the abundance or compositional diversity of microbes and ARGs while adjusting for covariates.

Results
By 1 year, the abundance of multiple species and ARGs differed by antibiotic exposure. Compared to infants never exposed to antibiotics, Bacteroides vulgatus relative abundance increased by 1.72% (95% CI: 0.19, 3.24) while Bacteroides fragilis decreased by 1.56% (95% CI: −4.32, 1.21). Bifidobacterium species also exhibited opposing trends. ARGs associated with exposure included class A beta-lactamase gene CfxA6. Among infants attending day care, Escherichia coli and ARG abundance were both positively associated with antibiotic use.

Conclusion
Novel findings, including the importance of day care attendance, were identified through considering microbiome data at baseline and post-intervention. Thus, our study design and approach have important implications for future studies evaluating the unintended impacts of antibiotics.

https://www.nature.com/articles/s41390-022-02104-w