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In severe bronchiolitis, recent evidence suggests distinct pathobiological roles of microbiota (e.g., viruses, bacteria) and host responses influenced by genetic and epigenetic factors. However, the relationship of airway microbiota with host DNA methylation (DNAm) in infants with severe bronchiolitis remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a multi\u2010center prospective cohort of 504 multi\u2010ethnic infants with severe bronchiolitis (age &lt;\u20091\u2009year), using nasopharyngeal microbiome (exposure) and blood DNAm (outcome, Infinium MethylationEPIC BeadChip, Illumina) data within 24\u2009h of the hospitalization, we conducted microbiome\u2010epigenome\u2010wide association studies (mbEWAS). We examined microbiota\u2010associated differentially methylated CpGs (mbDMCs, false discovery rate [FDR]\u2009&lt;\u20090.05), regions (mbDMRs, FDR &lt;\u20090.05), and DNAm age acceleration. We also determined the associations of DNAm age acceleration with asthma development by age 6\u2009years. Furthermore, we focused on asthma\u2010related pathogenic bacteria\u2014\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      <\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Moraxella catarrhalis<\/jats:italic>\n                      <\/jats:styled-content>\n                      , and\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">Streptococcus pneumoniae<\/jats:styled-content>\n                        \u2014\n                      <\/jats:italic>\n                      for functional analyses by examining serum mbDMR\u2010related proteins (Proseek Multiplex, Olink) and their enriched pathways (FDR &lt;\u20090.10).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across 23 common taxa\u2014observed at least in 25% of the infants, we identified 1 mbDMC (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>S. pneumoniae<\/jats:italic>\n                      <\/jats:styled-content>\n                      , cg16594639, chr20: 39528675) and 96 mbDMRs (e.g.,\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>S. pneumoniae<\/jats:italic>\n                      <\/jats:styled-content>\n                      , chr5:27038497\u201327038802,\n                      <jats:italic>CDH9<\/jats:italic>\n                      ; chr6:48068669\u201348068940,\n                      <jats:italic>PTCHD4<\/jats:italic>\n                      ). A higher\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>H. influenzae<\/jats:italic>\n                      <\/jats:styled-content>\n                      abundance was associated with DNAm age deceleration, and the deceleration was associated with a higher risk of developing asthma. In 29 mbDMRs of the asthma\u2010related pathogenic bacteria, we identified 156 mbDMR\u2010related proteins (e.g., MMP9, XCL1). These proteins were enriched in immune response\u2010related pathways (e.g., regulation of ERBB signaling and eosinophil chemotaxis and migration pathways).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this multi\u2010center prospective cohort study of severe bronchiolitis, our mbEWAS suggested the microbiota\u2010host associations that regulate immune responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70102","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:15:53Z","timestamp":1760404553000},"page":"764-780","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nasopharyngeal Microbiome\u2010Epigenome\u2010Wide Association Analysis in Infants With Severe Bronchiolitis"],"prefix":"10.1111","volume":"81","author":[{"given":"Ryohei","family":"Shibata","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T.H. 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