Breastfeeding and early Bifidobacterium-driven microbial colonization shape the infant gut resistome

The first year of life is a critical period for the acquisition and establishment of the infant gut resistome, as microbiome development is directly influenced by perinatal factors to which the neonate is exposed, such as feeding type or antibiotic use. This study aims to analyze the evolution of the infant resistome during the first year of life and to provide further insight into how breastfeeding may modulate the acquisition of antimicrobial resistance. A longitudinal metagenomic study of the gut microbiome was conducted 265 gut longitudinal metagenomes from 66 mother-infant pairs from the MAMI cohort (at 7 days, 1, 6, and 12 months of age). Detailed clinical data from mother–infant pairs were also collected, including mode of delivery, antibiotic use during delivery, and feeding practices. The microbial profile obtained after high-throughput sequencing (Illumina) was analyzed using the MetaPhlAn tool, while the resistome was characterized using ResFinder. Statistical analyses were performed using R software. During the first year of life, the diversity of antibiotic resistance genes (ARGs) increased, with tetracycline and aminoglycoside resistance genes being the most abundant. The composition of the infant microbiome was classified into two groups based on the abundance of the genus Bifidobacterium: high abundance (High-Bifidobacterium, HB) and low abundance (Low-Bifidobacterium, LB). Infants in the LB group exhibited higher levels of ARG abundance, mainly associated with species such as Escherichia coli and Klebsiella pneumoniae, which were the primary carriers of resistance. Exclusive breastfeeding during the first month of life mitigated the effects of cesarean delivery on the infant resistome, reducing ARG load. Exclusive breastfeeding during the first month of life is essential in shaping the infant resistome. By promoting a microbiome enriched in Bifidobacterium, breastfeeding may help suppress ARG-carrying taxa, reducing the risk of resistance dissemination. Our findings underscore the importance of breastfeeding as a natural intervention to shape the infant microbiome and resistome. Supporting breastfeeding through public health policies could help limit the spread of antimicrobial resistance in early life.