Dysbiosis of gut microbiota and resistome in antibiotic-treated paediatric Mycoplasma pneumoniae pneumonia: A 16S-metagenomics-metabolomics study

This study systematically investigates the compositional and functional alterations in gut microbiota and their metabolic profiles among healthy children (Group C), Mycoplasma pneumoniae (MP)-infected pneumonia patients (Group MP), and cohorts treated with azithromycin (Group AC) or ceftriaxone (Group CE). Utilizing 16S rRNA gene sequencing, metagenomic sequencing, and metabolomics, we characterized microbial diversity and metabolite dynamics. Compared to controls, the MP, AC, and CE groups exhibited a significant reduction in microbial richness and diversity. Notably, Bifidobacterium lemurum was markedly depleted in patient groups, suggesting its potential role in maintaining gut homeostasis. The abundance of ErmX, a macrocyclic antibiotic resistance genes, was increased in the patients of AC group that treated with azithromycin. The abundance of CTX-M-14(a beta-lactamase ARGs) was increased in patients of CE group that treated with ceftriaxone. Glycoside hydrolases 1 and glycosyltransferase 5, belonging to Carbohydrate active enzymes that may assisted the pathogen frequently cross the mucosal barrier during infection, are enriched in the MP group. Metabolomic analysis identified 561 differentially abundant metabolites. Arachidonic acid derivatives (prostaglandins A2/B2/I2), critical for inflammatory regulation, were depleted in Group MP but restored in Group AC. Group AC exhibited elevated Tyr-Tyr levels, inversely correlated with Klebsiella michiganensis abundance, an emerging opportunistic pathogen. Group CE showed unique accumulation of glycocholic acid hydrate, a hepatotoxic metabolite linked to ceftriaxone metabolism. The production of harmful metabolites may arise from antibiotic misuse. These findings suggest that medication for Mycoplasma pneumoniae infection can lead to multiple outcomes such as drug resistance and immune escapes, so that appropriate antibiotics and beneficial flora should be selected for treatment.