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

Abstract

Background: The effects of antibiotic use on children's gut microbiomes and resistomes are not well characterized in middle-income countries, where pediatric antibiotic consumption is exceptionally common. We characterized the effects of antibiotics commonly used by Peruvian children (i.e., amoxicillin, azithromycin, cefalexin, sulfa-trimethoprim) on gut diversity, genera, and antibiotic resistance gene (ARG) abundance from 3-16 months. Methods: This study included 54 children from a prospective cohort of enteric infections in peri-urban Lima, 2016-2019. Stool 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, the association of recent antibiotic use with species richness, diversity, gut genera, and ARG abundance over time was examined. Results: Most children were vaginally delivered (73%), received breastmilk almost daily over the study period, and belonged to socioeconomically diverse households. Amoxicillin, azithromycin, cefalexin, and sulfa-trimethoprim did not impact gut diversity or genera abundance. Azithromycin use significantly impacted ARGs from the macrolide, aminoglycoside, and folate pathway antagonist classes. Amoxicillin use significantly increased total ARGs. Antibiotics' effects on ARGs appeared to be independent of gut microbiome changes. Conclusion: Common antibiotics like amoxicillin and azithromycin may be key drivers of the gut resistome but not the microbiome during early childhood in this setting with frequent breastfeeding.