| Sumario: | Lower respiratory tract infections (LRTIs) are a leading cause of critical illness and mortality. The lung microbiome represents an important reservoir for the exchange of antibiotic resistance genes (ARGs). The pathogenic microbes remain poorly understood among different age groups, including children (0–17 years), youth (18–39 years), middle‐aged adults (40–64 years), and older adults (65–99 years). We conducted a retrospective study of 699 bronchoalveolar lavage fluid (BALF) samples from LRTI patients aged 30 days to 99 years. The differences in the lung microbiome and ARG expression shift with age were evaluated based on targeted next‐generation sequencing (tNGS) results. Correlation analysis revealed that age had a strongly positive correlation effect on the relative abundances of Candida albicans, Candida glabrata, Corynebacterium striatum, and Stenotrophomonas maltophilia. Meanwhile, age had a largely negative correlation effect on Enterococcus faecium and Mycoplasma pneumoniae. We found that ARG expression was significantly higher in adults compared with children. The beta‐lactam ARG TEM was the most abundant, and the primary carrier of ARGs was Streptococcus in the LRTI microbiota. The proportion of adults expressing beta‐lactams, aminoglycosides, and phenicol antibiotic types was higher compared to children. Our results indicated that ARGs in the human LRTI microbiota accumulate and become more complex with age, as older groups tend to harbor the highest abundance of these genes. Collectively, these results presented the respiratory tract core microbiota and ARGs in different age groups, supplying a foundation for microbiome‐targeted interventions and emphasizing the potential of tNGS to improve clinical diagnosis.
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