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Abstract Background In environmental bacteria, the selective advantage of antibiotic resistance genes (ARGs) can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes (VGs). The gut microbiome of infants has been shown to contain numerous ARGs, however, co-localization related to ARGs is unknown during early life despite frequent exposures to biocides and metals from an early age. Results 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. Statistical models showed that co-localization occurred mainly in the phylum Proteobacteria independent of high ARG content and contig length. We evaluated the stochasticity of co-localization occurrence using enrichment scores. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes, 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 VGs was associated with low gut microbial maturity and that VGs showed even higher potential for mobility than ARGs. Conclusions We found that the phenomenon of co-localization between ARGs and other resistance and VGs was prevalent in the gut at the beginning of life. It reveals the diversity that sustains antibiotic resistance and therefore indirectly emphasizes the need to apply caution in the use of antimicrobial agents in clinical practice, animal husbandry, and daily life to mitigate the escalation of resistance. Video Abstract

Abstract Background Growing up with siblings has been linked to numerous health outcomes and is also an important determinant for the developing microbiota. Nonetheless, research into the role of having siblings on the developing microbiota has mainly been incidental. Results Here, we investigate the specific effects of having siblings on the developing airway and gut microbiota using a total of 4497 hypopharyngeal and fecal samples taken from 686 children in the COPSAC2010 cohort, starting at 1 week of age and continuing until 6 years of age. Sibship was evaluated longitudinally and used for stratification. Microbiota composition was assessed using 16S rRNA gene amplicon sequencing of the variable V4 region. We found siblings in the home to be one of the most important determinants of the developing microbiota in both the airway and gut, with significant differences in alpha diversity, beta diversity, and relative abundances of the most abundant taxa, with the specific associations being particularly apparent during the first year of life. The age gap to the closest older sibling was more important than the number of older siblings. The signature of having siblings in the gut microbiota at 1 year was associated with protection against asthma at 6 years of age, while no associations were found for allergy. Conclusions Having siblings is one of the most important factors influencing a child’s developing microbiota, and the specific effects may explain previously established associations between siblings and asthma and infectious diseases. As such, siblings should be considered in all studies involving the developing microbiota, with emphasis on the age gap to the closest older sibling rather than the number of siblings. Video abstract