Prevotella melaninogenica Alleviate Mycoplasma pneumoniae Infection Through the Butyrate Based on Multi-Omic Analysis and Experimental Validation.

Mycoplasma pneumoniae (MP) is one of the main pathogens causing atypical pneumonia in children. The susceptible population is mainly children and adolescents over 5 years old, and the infection rate has increased in recent years. At present, there is limited research on the pulmonary microbiota of patients with Mycoplasma pneumoniae pneumonia, and the characteristics of their microbiota are not yet clear. We included MPP children in stages and established two independent cohorts. Cohort I (n = 175) performed 16S rRNA sequencing on bronchoalveolar lavage fluid (BALF) to explore microbial genus level characteristics, while Cohort II (n = 41) performed metagenomic and transcriptome sequencing to explore microbial species level characteristics and predict inter group differential metabolic pathways. Finally, a murine model infected with MP was established to validate the effects of Prevotella melaninogenica and its metabolite butyrate. Based on Multi-Omic Analysis, we discovered that P. melaninogenica was the most discriminative species enriched in the critically ill group. Functional profiling demonstrated that butanoate metabolism pathways were significantly enriched in the severe group and positively correlated with P. melaninogenica abundance. Transcriptomic analysis revealed that P. melaninogenica-associated host genes were significantly enriched in immune regulation pathways. Animal experiments confirmed that both P. melaninogenica and butyrate pretreatment significantly attenuated MP-induced pulmonary inflammation, pathogen load, and immune cell infiltration. Respiratory microbiota dysbiosis may be associated with MPP severity. Prevotella melaninogenica, a potential protective commensal enriched in severe group MPP patients, may alleviate airway inflammation through its metabolite butyrate.