Effects of commonly used antibiotics on children’s developing gut microbiomes and resistomes in peri-urban Lima, Peru

Background The effects of antibiotic use on children’s gut microbiomes and resistomes are not well characterized in middle-income countries, where antibiotic consumption is exceptionally common. Objectives We characterized the effects of antibiotics commonly used by Peruvian children (i.e. amoxicillin, azithromycin, cefalexin, trimethoprim/sulfamethoxazole) on the α-diversity, β-diversity and abundance of gut genera and antibiotic resistance genes (ARGs) from 3 to 16 months. Methods This study included 54 children from a prospective cohort of enteric infections in peri-urban Lima, 2016–19. Stools collected at 3, 6, 7, 9, 12 and 16 months underwent DNA extraction and short-read metagenomic sequencing. We profiled the taxonomy of stool metagenomes and assessed ARG abundance by aligning reads to the ResFinder database. We used daily surveillance data (40 662 observations) to tabulate the number of antibiotic courses consumed in the 30 days prior to stool sampling. Using linear mixed models, we examined associations of recent antibiotic use with richness, diversity and abundance of gut genera and ARGs over time. Results Each additional recent antibiotic course decreased Bifidobacterium and Dialister abundance and increased Veillonella abundance, although gut richness and diversity were not affected. Recent use of amoxicillin, azithromycin, cefalexin or trimethoprim/sulfamethoxazole, specifically, did not impact gut microbiome measures. Amoxicillin, azithromycin and trimethoprim/sulfamethoxazole significantly enriched multiple ARGs and amoxicillin use significantly increased total ARGs. Conclusions Common antibiotics like amoxicillin and azithromycin appear to be key drivers of the paediatric gut resistome. Resistome perturbations appeared to be stronger, or persist for longer, than gut microbiome effects in this middle-income country setting.