Abstract

Even in the absence of antibiotic exposure, the gut microbiome of infants has been shown to contain numerous antibiotic resistance genes (ARGs), but the mechanism for this remains unclear. In environmental bacteria, the selective advantage of ARGs can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes. However, this phenomenon is unknown from the human gut microbiome during early life despite frequent exposures to biocides and metals from an early age. Here, we conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation. Our study showed that co-localization of ARGs with other resistance and virulence genes is common in the early gut microbiome and is associated with gut bacteria that are indicative of low maturity, especially E. coli. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes located near other ARGs, and, on plasmids, co-localization predominantly occurred in the form of class 1 integrons. Antibiotic use caused a short-term increase in mobile ARGs, while non-mobile ARGs showed no significant change. Finally, we found that a high abundance of virulence genes was associated with low gut microbial maturity and that virulence genes showed even higher potential for mobility than ARGs. Our study highlights important constraints that need to be considered when developing strategies to combat ARG dissemination.