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

IntroductionCommensal bacterial community along the upper respiratory tract functions against pathogens. The host determinants of Mycoplasma pneumoniae severity should be identified against the increasing threat of macrolide-resistant M. pneumoniae (MRMP) infection. We hypothesized that respiratory...

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Main Authors: Wei-Chao Liao, Shiao-Wen Li, En-Wei Hsing, Sung-Han Hsiao, Ian Yi-Feng Chang, Yin-Cheng Chen, Yi-Yin Chen, Yi-Jiun Pan, Yu-Chia Hsieh
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Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1537182/full
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author Wei-Chao Liao
Wei-Chao Liao
Shiao-Wen Li
En-Wei Hsing
Sung-Han Hsiao
Ian Yi-Feng Chang
Yin-Cheng Chen
Yi-Yin Chen
Yi-Jiun Pan
Yu-Chia Hsieh
author_facet Wei-Chao Liao
Wei-Chao Liao
Shiao-Wen Li
En-Wei Hsing
Sung-Han Hsiao
Ian Yi-Feng Chang
Yin-Cheng Chen
Yi-Yin Chen
Yi-Jiun Pan
Yu-Chia Hsieh
author_sort Wei-Chao Liao
collection DOAJ
description IntroductionCommensal bacterial community along the upper respiratory tract functions against pathogens. The host determinants of Mycoplasma pneumoniae severity should be identified against the increasing threat of macrolide-resistant M. pneumoniae (MRMP) infection. We hypothesized that respiratory microbiome is involved in the clinical manifestations of M. pneumoniae infection.MethodsFrom 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, n = 57) and the cured control without fever or doxycycline treatment (WDT, n = 35) by using 16S rRNA-based sequencing and untargeted metabolome analysis.ResultsSignificantly higher diversity and different respiratory microbiomes were evaluated in WDT patients in contrast to DT patients. Fusobacterium, Haemophilus, Gemella, Oribacterium, Actinomyces lingnae, Fusobacterium periodonticum, Gemella sanguinis, and Solobacterium moorei 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. F. periodonticum abundance was negatively associated with an inflammatory metabolite: a platelet-activating factor. Fusobacterium and Oribacterium were related to the decrease in LysoPE(18:1(9Z)/0:0) and LysoPC(18:1(9Z)).ConclusionsMicrobiota 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 M. pneumoniae infection.
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spelling doaj-art-2a84ff8859714ddc83a80f91d996ed4f2025-08-20T03:34:30ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-07-011510.3389/fcimb.2025.15371821537182Respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide-resistant Mycoplasma pneumoniae-mediated pneumoniaWei-Chao Liao0Wei-Chao Liao1Shiao-Wen Li2En-Wei Hsing3Sung-Han Hsiao4Ian Yi-Feng Chang5Yin-Cheng Chen6Yi-Yin Chen7Yi-Jiun Pan8Yu-Chia Hsieh9Molecular Medicine Research Center, Chang Gung University, Taoyuan, TaiwanDepartment of Pediatrics, Chang Gung Children’s Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, TaiwanDepartment of Life Sciences, National University of Kaohsiung, Kaohsiung, TaiwanDepartment of Pediatrics, Chang Gung Children’s Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, TaiwanDivision of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, TaiwanMolecular Medicine Research Center, Chang Gung University, Taoyuan, TaiwanInstitute of BioMedical Informatics, National Yang Ming Chiao Tung University, Taipei, TaiwanGraduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Microbiology and Immunology, School of Medicine, College of Medicine, China Medical University, Taichung, TaiwanDepartment of Pediatrics, Chang Gung Children’s Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, TaiwanIntroductionCommensal bacterial community along the upper respiratory tract functions against pathogens. The host determinants of Mycoplasma pneumoniae severity should be identified against the increasing threat of macrolide-resistant M. pneumoniae (MRMP) infection. We hypothesized that respiratory microbiome is involved in the clinical manifestations of M. pneumoniae infection.MethodsFrom 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, n = 57) and the cured control without fever or doxycycline treatment (WDT, n = 35) by using 16S rRNA-based sequencing and untargeted metabolome analysis.ResultsSignificantly higher diversity and different respiratory microbiomes were evaluated in WDT patients in contrast to DT patients. Fusobacterium, Haemophilus, Gemella, Oribacterium, Actinomyces lingnae, Fusobacterium periodonticum, Gemella sanguinis, and Solobacterium moorei 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. F. periodonticum abundance was negatively associated with an inflammatory metabolite: a platelet-activating factor. Fusobacterium and Oribacterium were related to the decrease in LysoPE(18:1(9Z)/0:0) and LysoPC(18:1(9Z)).ConclusionsMicrobiota 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 M. pneumoniae infection.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1537182/fullMycoplasma pneumoniaepneumoniarespiratorymicrobiomemetabolomemacrolide-resistant Mycoplasma pneumoniae
spellingShingle Wei-Chao Liao
Wei-Chao Liao
Shiao-Wen Li
En-Wei Hsing
Sung-Han Hsiao
Ian Yi-Feng Chang
Yin-Cheng Chen
Yi-Yin Chen
Yi-Jiun Pan
Yu-Chia Hsieh
Respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide-resistant Mycoplasma pneumoniae-mediated pneumonia
Frontiers in Cellular and Infection Microbiology
Mycoplasma pneumoniae
pneumonia
respiratory
microbiome
metabolome
macrolide-resistant Mycoplasma pneumoniae
title Respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide-resistant Mycoplasma pneumoniae-mediated pneumonia
title_full Respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide-resistant Mycoplasma pneumoniae-mediated pneumonia
title_fullStr Respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide-resistant Mycoplasma pneumoniae-mediated pneumonia
title_full_unstemmed Respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide-resistant Mycoplasma pneumoniae-mediated pneumonia
title_short Respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide-resistant Mycoplasma pneumoniae-mediated pneumonia
title_sort respiratory microbiome and metabolome features associate disease severity and the need for doxycycline treatment in children with macrolide resistant mycoplasma pneumoniae mediated pneumonia
topic Mycoplasma pneumoniae
pneumonia
respiratory
microbiome
metabolome
macrolide-resistant Mycoplasma pneumoniae
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1537182/full
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