The infant gut resistome is associated with E. coli and early-life exposures

Abstract

Background 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. Results 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. Conclusions 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.

Metagenomic analysis reveals associations between salivary microbiota and body composition in early childhood

“…Negative control yields were too low to quantify at 2 µl. Extracted DNA was amplified from all samples were prepared for sequencing on the NextSeq platform (shotgun metagenomics) using 150 nt paired end reads at the Marine Biological Laboratory (MBL) in Woods Hole, MA using established methods and as previously published 23 – 25 , 28 .…”

“…This was directly examined in our prospective analyses by assessing child growth between 0 and 2 years of age. Based on the DAG, the potential confounders (i.e., related to our exposure and outcome directly or hypothesized to be based on previously identified indirect associations in separate studies) to adjust for in our analyses were age (measured by age in days of the saliva sample), sex (male or female) 24 , 41 , delivery mode (vaginal or cesarean delivery) 3 , gestational age (age in weeks) 27 , 28 and diet (age when child started to eat solid foods in months) 41 . Although previous studies have found associations between maternal BMI or weight gain and children’s BMI 73 , literature identifying associations between maternal BMI and the child’s saliva microbiome have not found associations 41 , 74 .…”

“…High BMI in preschool years (and not later in childhood) has been shown to be associated with a higher risk of overweight or obesity in adolescence among children who had had stable BMI 22 . Therefore, in examining the salivary microbiota of approximately 4-year-old children enrolled in an ongoing prospective cohort, the New Hampshire Birth Cohort (NHBCS) 23 – 28 , we aimed to investigate whether the salivary microbiota was associated with concurrent body weight metrics (overweight status or body fat mass). For a subset of participating children, we examined the potential impact of early growth exposure metrics prior to sample collection (weight trajectory up to age 2) on the salivary microbiota.…”

Next-generation sequencing and PCR technologies in monitoring the hospital microbiome and its drug resistance

“…Metagenomics has been broadly applied for the study of the resistome of the human and animal microbiome ( Afridi et al, 2020 , 2021 ; Caselli et al, 2020 ), and of that from different habitats, including agricultural and urban soils ( Crofts et al, 2017 ). It has also been applied for local and international AMR surveillance of specific strains, mostly associated with HAI onset, such as carbapenem and quinolone-resistance Gram-negative bacteria, multi-resistant S. aureus and Enterobacterales , and M. tuberculosis ( Soliman et al, 2020 ; Lebeaux et al, 2021 ; Vazquez-Lopez et al, 2021 ; Waddington et al, 2022 ). Interestingly, by using a metagenomic approach, it was possible to show that more confined and cleaned environments had reduced microbial diversity and increased resistance, suggesting the implementation of strategies to restore bacterial diversity in certain built environments ( Mahnert et al, 2019 ).…”

Impact of intrapartum antibiotics on the developing microbiota: a review

“…children at 2-5 years [32] . Beyond gut microbiota, some studies have also been published showing differences in the infant oral microbiota due to maternal intrapartum antibiotics [33,34] .…”