{
  "abstract": "Background Severe asthma is a heterogeneous condition encompassing multiple phenotypes. Understanding lung-specific mechanisms in children with severe asthma may enable the development of more precise therapeutic strategies. We previously reported that immune components in bronchoalveolar lavages (BALs) differentiate children with severe asthma from non-asthmatic disease-controls and, frequent from non-frequent exacerbators, among children with severe asthma. Objective To identify a local signature of severe asthma using complementary multi-omics analyses of BALs. A secondary objective was to evaluate whether bacterial taxa and metabolites discriminate severe asthma subtypes associated with distinct phenotypes or endotypes. Methods BAL microbiome and metabolome were investigated in 20 children with severe asthma and 10 non-asthmatic children using 16S rRNA gene amplicon sequencing and liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), respectively. Data were analysed separately and through integrative multi-omics approaches. Results Compared with controls, BALs from children with severe asthma showed increased alpha-diversity, higher relative abundances of Actinobacteriota , Streptococcus , Moraxella , Corynebacterium , Tropheryma , and Treponema , and an altered polyamine pathway characterized by reduced arginine and increased spermine and spermidine levels. Integrated analyses revealed significant associations between Streptococcus and both spermine and spermidine. Independently, each dataset discriminated severe asthma phenotypes, notably exacerbation frequency and co-occurring atopic dermatitis. Unsupervised clustering of microbiome profiles identified four distinct clusters that may reflect severe asthma endotypes. Conclusions This study identifies a distinct airway microbiome–metabolome signature associated with pediatric severe asthma. Enrichment of specific bacterial taxa, particularly Streptococcus , together with altered polyamine metabolic pathway, highlights microbial–metabolic interactions potentially involved in disease pathophysiology. The ability of microbiome and metabolome profiles to independently and jointly discriminate clinical phenotypes underscores the relevance of multi-omics approaches for diagnosis and follow-up of severe asthma. Our findings support the importance of airway-level profiling to improve mechanistic understanding of severe asthma and inform on future targeted therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Mélanie Briard"
    },
    {
      "name": "Blanche Guillon"
    },
    {
      "name": "Eric Venot"
    },
    {
      "name": "Marta Grauso"
    },
    {
      "name": "Christelle Hennequet-Antier"
    },
    {
      "name": "Aurélia Bruneau"
    },
    {
      "name": "François Fenaille"
    },
    {
      "name": "Florence Castelli"
    },
    {
      "name": "Muriel Thomas"
    },
    {
      "name": "Guillaume Lezmi"
    },
    {
      "name": "Maria Leite-De-Moraes"
    },
    {
      "name": "Karine Adel-Patient"
    },
    {
      "name": "Vinciane Saint-Criq"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ew6r281tf6sg2.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358560",
  "fulltext_url": null,
  "id": "ew6r281tf6sg2",
  "issns": [
    "1932-6203",
    "1932-6203"
  ],
  "landing_url": "https://hal.inrae.fr/hal-05759588v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2737|Asthma and respiratory diseases"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Amino acid metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Metabolic pathways"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Metabolites"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Metabolomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Microbial genomics/Microbiome"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Streptococcus"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbiome"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Microbial genomics/Microbiome"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Streptococcus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Respiratory disorders/Asthma"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Streptococcus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pediatrics"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pulmonology/Respiratory disorders/Asthma"
    ]
  ],
  "openalex": "W7213554319",
  "pdf_url": "https://hal.inrae.fr/hal-05759588/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/ew6r281tf6sg2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "hal-05759588",
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      "url": "https://hal.inrae.fr/hal-05759588v1"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:metabolism",
      "subfield": "enzymology-metabolism"
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    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
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  ],
  "title": "A microbiome–metabolome signature associated with pediatric severe asthma",
  "title_text": "A microbiome–metabolome signature associated with pediatric severe asthma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/ew6r281tf6sg2",
  "venue": "PLoS ONE",
  "versions": []
}