Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome

Abstract

Development of the preterm infant gut microbiota is emerging as a critical research priority1. Since preterm infants almost universally receive early and often extended antibiotic therapy2, it is important to understand how these interventions alter gut microbiota development3-6. Analysis of 401 stools from 84 longitudinally sampled preterm infants demonstrates that meropenem, cefotaxime and ticarcillin–clavulanate are associated with significantly reduced species richness. In contrast, vancomycin and gentamicin, the antibiotics most commonly administered to preterm infants, have non-uniform effects on species richness, but these can be predicted with 85% accuracy based on the relative abundance of only two bacterial species and two antibiotic resistance (AR) genes at treatment initiation. To investigate resistome development, we functionally selected resistance to 16 antibiotics from 21 faecal metagenomic expression libraries. Of the 794 AR genes identified, 79% had not previously been classified as AR genes. Combined with deep shotgun sequencing of all stools, we find that multidrug-resistant members of the genera Escherichia, Klebsiella and Enterobacter, genera commonly associated with nosocomial infections, dominate the preterm infant gut microbiota. AR genes that are enriched following specific antibiotic treatments are generally unique to the specific treatment and are highly correlated with the abundance of a single species. The most notable exceptions include ticarcillin–clavulanate and ampicillin, both of which enrich for a large number of overlapping AR genes, and are correlated with Klebsiella pneumoniae. We find that all antibiotic treatments are associated with widespread collateral microbiome impact by enrichment of AR genes that have no known activity against the specific antibiotic driver.

Identical bacterial populations colonize premature infant gut, skin, and oral microbiomes and exhibit different in situ growth rates

“…Given that 98.7% of all reads mapped to 12 reconstructed bacterial and 18 phage/plasmid genomes from Infant 1, and 95.0% to 14 bacterial and 21 phage/plasmid genomes from Infant 2, we conclude that the majority of the community was accounted for. This result confirms the overall low diversity of the early community when compared to full-term infants Gibson et al 2016;Ward et al 2016). Overlap of strains across body sites contributes to the low total diversity of these premature infant microbiomes compared to those of other infants.…”

“…Previous studies have described the gut microbiome of premature infants as relatively simple and prone to rapid changes in composition Gibson et al 2016;Ward et al 2016). To our knowledge, this is the first study to investigate the body habitat range of individual genotypes and to compare microbial activity of the same populations across body sites.…”

Impact of maternal nutrition in pregnancy and lactation on offspring gut microbial composition and function

“…The importance of microbiota to human health and disease has come into the scientific spotlight within the last decade, [18][19][20][21][22] and major questions surround how and when we acquire our microbiota. [23][24][25][26][27] It is widely recognized that microbial transmission of bacteria from mother to offspring is essential for the establishment and development of a healthy nascent microbiome, which may impact infant growth, [28][29][30] immune system maturation [31][32][33][34][35] and even neurodevelopment. 36,37 Interestingly, emerging evidence has additionally indicated that transmission of microbiota from mother to offspring may occur before delivery, which has since reemphasized the importance of the pregnancy period to the development of the neonatal microbiome.…”

Antibiotic perturbation of the preterm infant gut microbiome and resistome

“…35,36 Gibson et al recently used this suite of techniques to develop a sequence-unbiased account of the effects of antibiotic therapy on the preterm infant microbiota with respect to phylogeny and antibiotic resistance gene distribution. 37 A longitudinal, sequencing based interrogation of the preterm infant gut microbiota…”