{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:56:01Z","timestamp":1777870561692,"version":"3.51.4"},"posted":{"date-parts":[[2025,8,19]]},"group-title":"Respiratory Medicine","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Early-life susceptibility to viral respiratory infections is associated with long-term respiratory morbidity in children. Currently, no reliable tools exist to predict susceptibility to these infections. Because the endogenous microbiota can influence pathogen virulence and airway inflammation, it represents a potential target for prevention. In this pilot study, we hypothesised that distinct nasal microbial communities are associated with susceptibility to viral respiratory infections and wheezing outcomes during the first year of life.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We analyzed 90 nasal swabs from 55 infants enrolled in the AERIAL study, representing asymptomatic samples collected at scheduled visits (\u223c4 months) and symptomatic samples. Bacterial profiling was done blind to clinical data using full-length\n                    <jats:italic>16S rRNA<\/jats:italic>\n                    sequencing, and bacterial load was quantified using a pan-bacterial TaqMan\u00ae assay.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Bacterial diversity was similar between asymptomatic and symptomatic swabs, with community composition differences largely driven by inter-individual variation. In paired samples, symptomatic swabs showed reduced diversity but no change in bacterial load. Virus-bacteria interactions were observed in rhinovirus-positive swabs, but not SARS-CoV-2-positive swabs. Two nasal endotypes were identified, dominated by\n                    <jats:italic>Moraxella<\/jats:italic>\n                    or\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    and differing in alpha diversity. Endotypes were associated with age at wheeze onset, and their relationship with wheezing episode rates showed a suggestive sex-dependent pattern that warrants further investigation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our pilot data suggest that the nasal microbiota might shape early wheezing outcomes in a sex-dependent manner, and highlight the value of longitudinal studies for clarifying how host-bacteria-virus interactions in early life.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>What is tested<\/jats:title>\n                  <jats:p>Whether distinct nasal microbiota endotypes in infancy are associated with later respiratory phenotypes, particularly wheeze.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>What the study showed<\/jats:title>\n                  <jats:p>Two endotypes were identified. Moraxella-dominated and Streptococcus-dominated, with differences in alpha diversity and associations with age at wheeze onset and wheezing rates.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>The significance and clinical impact of the research outcomes<\/jats:title>\n                  <jats:p>Nasal microbiota endotypes may help identify infants at risk of wheeze and support early risk stratification, pending validation in larger cohorts.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.16.25333459","type":"posted-content","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T15:10:13Z","timestamp":1755616213000},"source":"Crossref","is-referenced-by-count":0,"title":["Insights into the relationship between nasal bacterial composition and susceptibility to early-life respiratory disease: a pilot observational study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-4952","authenticated-orcid":false,"given":"Jose A.","family":"Caparr\u00f3s-Mart\u00edn","sequence":"first","affiliation":[{"name":"UWA Medical School, UWA Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"Curtin Health and Innovation Research Institute (CHIRI), Curtin University, Perth, Western Australia, Australia"},{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Kicic-Starcevich","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3703-4111","authenticated-orcid":false,"given":"Patricia","family":"Agudelo-Romero","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"European Virus Bioinformatics Centre, Friedrich-Schiller-Universit\u00e4t Jena, 07737, Thuringia, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G","family":"Hancock","sequence":"additional","affiliation":[{"name":"UWA Medical School, UWA Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"Department of Sleep and Respiratory Medicine, Perth Children\u2019s Hospital, Perth, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Iosifidis","sequence":"additional","affiliation":[{"name":"UWA Medical School, UWA Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"School of Population Health, Curtin University, Bentley, Western Australia, Australia"},{"name":"Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2586-3358","authenticated-orcid":false,"given":"Yuliya V","family":"Karpievitch","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"School of Population Health, Curtin University, Bentley, Western Australia, Australia"},{"name":"School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6823-4696","authenticated-orcid":false,"given":"David J","family":"Martino","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guicheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"UWA Medical School, UWA Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"School of Population Health, Curtin University, Bentley, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desiree T","family":"Silva","sequence":"additional","affiliation":[{"name":"UWA Medical School, UWA Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"School of Population Health, Curtin University, Bentley, Western Australia, Australia"},{"name":"The Kids Research Institute Australia, The University of Western Australia, Nedlands, WA, Australia"},{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia"},{"name":"Department of Paediatrics and Neonatology, Joondalup Health Campus, Perth, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4335-615X","authenticated-orcid":false,"given":"Anthony","family":"Bosco","sequence":"additional","affiliation":[{"name":"Asthma and Airway Disease Research Center, The University of Arizona Tucson, Arizona"},{"name":"Department of Immunobiology, The University of Arizona College of Medicine Tucson, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L","family":"Prescott","sequence":"additional","affiliation":[{"name":"UWA Medical School, UWA Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"The Kids Research Institute Australia, The University of Western Australia, Nedlands, WA, Australia"},{"name":"Nova Institute for Health, Baltimore, Maryland, United States; Department of Family and Community Medicine, University of Maryland, Baltimore, Maryland, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter N","family":"LeSou\u00ebf","sequence":"additional","affiliation":[{"name":"UWA Medical School, UWA Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0008-9733","authenticated-orcid":false,"given":"Anthony","family":"Kicic","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Perth, Western Australia, Australia"},{"name":"School of Population Health, Curtin University, Bentley, Western Australia, Australia"},{"name":"Centre for Cell Therapy and 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