{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:51:02Z","timestamp":1787748662380,"version":"build-2784847793"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":1058,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08 HL141652"],"award-info":[{"award-number":["K08 HL141652"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08 HL151907"],"award-info":[{"award-number":["K08 HL151907"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL119280"],"award-info":[{"award-number":["R01 HL119280"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08 HL141652"],"award-info":[{"award-number":["K08 HL141652"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08 HL151907"],"award-info":[{"award-number":["K08 HL151907"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL119280"],"award-info":[{"award-number":["R01 HL119280"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bronchopulmonary dysplasia (BPD) is a common lung disease of premature infants. Hyperoxia exposure and microbial dysbiosis are contributors to BPD development. However, the mechanisms linking pulmonary microbial dysbiosis to worsening lung injury are unknown. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that regulates oxidative stress responses and modulates hyperoxia-induced lung injury. We hypothesized that airway dysbiosis would attenuate Nrf2-dependent antioxidant function, resulting in a more severe phenotype of BPD. Here, we show that preterm infants with a Gammaproteobacteria-predominant dysbiosis have increased endotoxin in tracheal aspirates, and mice monocolonized with the representative Gammaproteobacteria Escherichia coli show increased tissue damage compared with germ-free (GF) control mice. Furthermore, we show Nrf2-deficient mice have worse lung structure and function after exposure to hyperoxia when the airway microbiome is augmented with E. coli. To confirm the disease-initiating potential of airway dysbiosis, we developed a novel humanized mouse model by colonizing GF mice with tracheal aspirates from human infants with or without severe BPD, producing gnotobiotic mice with BPD-associated and non\u2013BPD-associated lung microbiomes. After hyperoxia exposure, BPD-associated mice demonstrated a more severe BPD phenotype and increased expression of Nrf2-regulated genes, compared with GF and non\u2013BPD-associated mice. Furthermore, augmenting Nrf2-mediated antioxidant activity by supporting colonization with Lactobacillus species improved dysbiotic-augmented lung injury. Our results demonstrate that a lack of protective pulmonary microbiome signature attenuates an Nrf2-mediated antioxidant response, which is augmented by a respiratory probiotic blend. We anticipate antioxidant pathways will be major targets of future microbiome-based therapeutics for respiratory disease.<\/jats:p>","DOI":"10.1165\/rcmb.2021-0508oc","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T11:56:45Z","timestamp":1666785405000},"page":"267-278","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":18,"title":["Microbial-induced Redox Imbalance in the Neonatal Lung Is Ameliorated by Live Biotherapeutics"],"prefix":"10.1093","volume":"68","author":[{"given":"Amelia E.","family":"Freeman","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent A.","family":"Willis","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Wenger","sequence":"additional","affiliation":[{"name":"Heersink School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Gaggar","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namasivayam","family":"Ambalavanan","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent E.","family":"Tipple","sequence":"additional","affiliation":[{"name":"Section of Neonatal-Perinatal Medicine, Department of Pediatrics, The University of Oklahoma Health Science Center, Oklahoma City, 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