Perinatal risk factors for fecal antibiotic resistance gene patterns in pregnant women and their infants

Abstract

Perinatal factors can shape fecal microbiome patterns among pregnant women and their infants. However, there is scarce information about the effect of maternal demographics and perinatal exposures on antibiotic resistance genes (ARG) and mobile genetic element (MGE) patterns in pregnant women and infants. We examined fecal samples from pregnant women during their third trimester of pregnancy (n = 51) and 6-month-old infants (n = 40). Of the 91 participants, 72 represented 36 maternal-infant dyads, 15 were additional pregnant women, and 4 were additional infants. We assessed the effects of demographics, pre-pregnancy BMI, smoking and parity in the pregnancy resistome and the effects of demographics, delivery mode, feeding habits and prenatal antibiotic treatment on the infancy resistome. ARG and MGE richness and abundance were assessed using a SmartChip qPCR-array. Alpha diversity (Shannon and Inverse Simpson index) and beta diversity (Sorensen and Bray-Curtis index) were calculated. The Wilcoxon and the Kruskal non-parametric test were used for comparisons. There is a high variability in shared resistome patterns between pregnant women and their infants. An average of 29% of ARG and 24% of MGE were shared within dyads. Infants had significantly greater abundance and higher diversity of ARG and MGE compared to pregnant women. Pregnancy and infancy samples differed in ARG and MGE gene composition and structure. Composition of the fecal resistome was significantly associated with race in pregnant women, with non-white women having different patterns than white women, and, in infants, with extent of solid food consumption. Our data showed that the pregnancy and infancy resistome had different structure and composition patterns, with maternal race and infant solid food consumption as possible contributors to ARG. By characterizing resistome patterns, our results can inform the mechanism of antibiotic resistome development in pregnant women and their infants.

The Infant Gut Resistome is Associated with E. coli and Early-life Exposures

“…Both studies also found MGEs to be at a greater abundance in infants as opposed to mothers. [14,19]. This notion that E. coli is important to the resistome and mobilome is also supported by the results of our MGE analysis as MGE relative abundance was associated with E. coli-speci c contributions especially regarding plasmid maintenance.…”

“…As E. coli contain a high diversity of plasmids and high potential for horizontal gene transfer [43], this is a particular concern. Two recent papers [14,19] did not directly identify an association between any speci c MGE and E. coli in the infant gut, but do provide additional context that support this study's ndings. Of particular interest, one study found that E. coli relative abundance was associated with an increased ARG relative abundance and that plasmids and other MGEs were at a higher relative abundance in infant guts at 1 month as opposed to 6 months [19].…”

“…Surprisingly, we identi ed that male sex was associated with a greater overall relative abundance of ARGs at 6 weeks, but with a decreased risk of unique ARGs at 1 year. A recent study [14] found that among 40 infants that were 6 months old, males had a higher richness of ARGs (de ned as the total prevalence of ARGs in each sample) but found no difference in the summed relative abundance. Another study [47] assessed sex differences in the gut resistome of adults.…”

“…Infants and young children are prescribed more antibiotics than any other age group [9,10]. Multiple studies have focused on understanding the role of early-life antibiotic exposures to the infant gut resistome noting enrichment for ARGs that did and did not confer resistance to the antibiotic prescribed [11][12][13][14]. Moreover, ARGs have been identi ed in infants' rst stools following delivery and prior to any direct antibiotic exposure [15][16][17].…”

“…Factors that have speci cally been assessed in relation to the infant gut resistome include age of the infant [11,18,19], type of delivery [15,20], breast versus formula feeding [21], gestational age [11,13,21], and intrapartum antibiotic usage [19]. Prior investigations assessing how early-life factors impact the resistome have focused on preterm infants [11,13,22] or were based on small cohorts (< 50) of full term infants [8,12,14,[17][18][19]. The two largest studies in full-term infants [15,20] reported on the count and types of ARGs but did not examine longitudinal changes in ARGs or early-life factors associated with resistome development.…”