부산대학교 도서관

The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants (N = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0–7) and a tetracycline‐mupirocin‐β‐lactam‐dominant phase (Months 8–14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with Escherichia (25.5%) harboring the most resistance genes. In a further analysis with all available infants (N = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years (p < 0.001). Using a random‐forest approach, a set of 34 resistance genes could be used to predict age (R2 = 68.0%). Leveraging microbial host inference analyses, we inferred the age‐dependent assembly of infant resistome was a result of shifts in the gut microbiome, primarily driven by changes in taxa that disproportionately harbor resistance genes across taxa (e.g., Escherichia coli more frequently harbored resistance genes than other taxa). We performed metagenomic functional profiling and metagenomic assembled genome analyses whose results indicate that the development of gut resistome was driven by changes in microbial carbohydrate metabolism, with an increasing need for carbohydrate‐active enzymes from Bacteroidota and a decreasing need for Pseudomonadota during infancy. Importantly, we observed increased acquired resistance genes over time, which was related to increased horizontal gene transfer in the developing infant gut microbiome. In summary, infant age was negatively correlated with antimicrobial resistance gene levels, reflecting a composition shift in the gut microbiome, likely driven by the changing need for microbial carbohydrate metabolism during early life. Highlights: We first examined the natural assembly of resistome in healthy infants' guts and identified resistance genes that were significantly impacted by age.We inferred that the age‐dependent assembly of infant resistome was a result of the shift of the gut microbiome, which was due to resistance genes being disproportionally distributed across taxa.Age‐dependent assembly of infant resistome reflected the shift in the gut microbiome, and such modifications were often a result of dietary transitions during infancy.Maturation of gut resistome was driven by infants' changing carbohydrate metabolism, which demonstrated an increasing need for carbohydrate‐active enzymes from Bacteroidota and decreasing involvements from Pseudomonadota during infancy. [ABSTRACT FROM AUTHOR]