The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling were used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs. Metagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks’ gestation) and 15 late preterm (33–36 weeks’ gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54–5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux. The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically Escherichia coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a trend towards a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97–1.29)] as well as having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12–1.84)] at 1 year compared to infants born vaginally. Our findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the risk of antibiotic resistant infections.

中文翻译：

---

婴儿肠道耐药组与大肠杆菌和生命早期接触有关

人类肠道微生物组包含一系列细菌抗菌素耐药基因 (ARG)，称为耐药组。生命早期与耐药组建立相关的因素尚不清楚。我们在美国的一个大型前瞻性队列中研究了与生命第一年的抗药性发育相关的早期暴露和分类学特征。使用鸟枪法宏基因组测序来分析从参加新罕布什尔州出生队列研究的婴儿在 6 周和 1 岁时收集的粪便样本中的微生物组成和 ARG。使用负二项回归和统计模型来检查婴儿因素，如性别、分娩方式、喂养方法、胎龄、抗生素暴露和婴儿肠道微生物组组成与 ARG 多样性和相对丰度的关系。对 195 名足月（至少妊娠 37 周）和 15 名晚期早产儿（妊娠 33-36 周）婴儿的配对样本进行了宏基因组测序。与 1 年样本相比，6 周样本的 ARG 携带率是 4.37 倍（95% CI：3.54-5.39）。大多数在 6 周时相对丰度较高的 ARG（卡方 p < 0.01）通过抗生素外流机制发挥作用。耐药组的总体相对丰度与肠道微生物组中变形菌的相对丰度（斯皮尔曼相关性 = 78.9%），特别是大肠杆菌（62.2%）的相对丰度密切相关。在婴儿特征中，分娩方式与 ARG 的多样性和相对丰度关系最为密切。通过剖腹产出生的婴儿有携带独特 ARG 的风险较高的趋势 [相对风险 = 1.12 (95% CI: 0.97–1.29)] 以及总体 ARG 相对丰度的风险增加 [相对风险 = 1.43 (95) 1 岁时与顺产婴儿相比，% CI：1.12–1.84)]。我们的研究结果表明，正在发育的婴儿肠道抵抗组可能会因生命早期的暴露而改变。确定婴儿特征和生命早期接触对耐药组的影响程度，最终可以采取干预措施，减少 ARG 的传播，从而降低抗生素耐药性感染的风险。