Respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide-resistant -mediated pneumonia.

INTRODUCTION

Commensal bacterial community along the upper respiratory tract functions against pathogens. The host determinants of severity should be identified against the increasing threat of macrolide-resistant (MRMP) infection. We hypothesized that respiratory microbiome is involved in the clinical manifestations of infection.

METHODS

From 2017 to 2020, 92 children with MRMP-mediated pneumonia were enrolled among 845 children with community-associated pneumonia. Oropharyngeal samplings were collected within 48 h after admission. We compared respiratory microbiome and metabolites based on patients' later development of prolonged fever and the need for doxycycline treatment (DT, = 57) and the cured control without fever or doxycycline treatment (WDT, = 35) by using 16S rRNA-based sequencing and untargeted metabolome analysis.

RESULTS

Significantly higher diversity and different respiratory microbiomes were evaluated in WDT patients in contrast to DT patients. , , , , , , , and were inversely correlated with disease severity. We assumed that metabolites of divergent microbiomes were related to MRMP development. We identified 15 discriminative amino-acid- and fatty-acid-related metabolites in two groups. abundance was negatively associated with an inflammatory metabolite: a platelet-activating factor. and were related to the decrease in LysoPE(18:1(9Z)/0:0) and LysoPC(18:1(9Z)).

CONCLUSIONS

Microbiota dysbiosis with dysregulated inflammatory glycerolphospholipid-related metabolites was related to disease severity and the need for doxycycline treatment in children with MRMP-mediated pneumonia. Anaerobic bacteria metabolites and metabolic pathway could be beneficial therapeutic targets against infection.