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New methods and technologies revealed distinct microbiome compositions and developmental trajectories in the differing parts of the respiratory tract of neonates and infants. In this review, we describe the current understanding of respiratory microbiota development in human neonates and highlight multiple factors that have been identified to impact human respiratory microbiome development including gestational age, mode of delivery, diet, antibiotic treatment, and early infections. Moreover, we discuss to date revealed respiratory microbiome\u2013disease associations in infants and children that may indicate a potentially imprinting cross talk between microbial communities and the host immune system in the respiratory tract. It becomes obvious how insufficient our knowledge still is regarding the exact mechanisms underlying such cross talk in humans. Lastly, we highlight strong findings that emphasize the important role of the gut\u2013lung axis in educating and driving pulmonary immunity. Further research is needed to better understand the host \u2013 respiratory microbiome interaction in order to enable the translation into microbiome\u2010based strategies to protect and improve human respiratory health from early childhood.<\/jats:p>","DOI":"10.1111\/apha.14266","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T06:18:59Z","timestamp":1737526739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The neonate respiratory microbiome"],"prefix":"10.1111","volume":"241","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3624-6251","authenticated-orcid":false,"given":"Sabine","family":"Pirr","sequence":"first","affiliation":[{"name":"Department of Pediatric Pneumology, Allergology and Neonatology Hannover Medical School  Hannover Germany"},{"name":"Cluster of Excellence RESIST 2155\u2014Resolving Infection Susceptibility, Hannover Medical School  Hannover 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