The fungal microbiota modulate neonatal oxygen-induced lung injury
Abstract Background The immature lungs of very preterm infants are exposed to supraphysiologic oxygen, contributing to bronchopulmonary dysplasia (BPD), a chronic lung disease that is the most common morbidity of prematurity. While the microbiota significantly influences neonatal health, the relatio...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s40168-025-02032-x |
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| author | Isaac Martin Mary Silverberg Ahmed Abdelgawad Kosuke Tanaka Brian A. Halloran Teodora Nicola Erin D. Myers Jay P. Desai Catrina T. White Ibrahim Karabayir Oguz Akbilgic Laura Tipton Samuel J. Gentle Namasivayam Ambalavanan Brian M. Peters Luan D. Vu Viral G. Jain Charitharth V. Lal Stephania A. Cormier Joseph F. Pierre Tamás Jilling Ajay J. Talati Kent A. Willis |
| author_facet | Isaac Martin Mary Silverberg Ahmed Abdelgawad Kosuke Tanaka Brian A. Halloran Teodora Nicola Erin D. Myers Jay P. Desai Catrina T. White Ibrahim Karabayir Oguz Akbilgic Laura Tipton Samuel J. Gentle Namasivayam Ambalavanan Brian M. Peters Luan D. Vu Viral G. Jain Charitharth V. Lal Stephania A. Cormier Joseph F. Pierre Tamás Jilling Ajay J. Talati Kent A. Willis |
| author_sort | Isaac Martin |
| collection | DOAJ |
| description | Abstract Background The immature lungs of very preterm infants are exposed to supraphysiologic oxygen, contributing to bronchopulmonary dysplasia (BPD), a chronic lung disease that is the most common morbidity of prematurity. While the microbiota significantly influences neonatal health, the relationship between the intestinal microbiome, particularly micro-eukaryotic members such as fungi and yeast, and lung injury severity in newborns remains unknown. Results Here, we show that the fungal microbiota modulates hyperoxia-induced lung injury severity in very low birth weight premature infants and preclinical pseudohumanized and altered fungal colonization mouse models. Instead of fungal communities dominated by Candida and Saccharomyces, the first stool microbiomes of infants who developed BPD had less interconnected community architectures with a greater diversity of rarer fungi. After using a pseudohumanized model to show that transfer to the neonatal microbiome from infants with BPD increased the severity of lung injury, we used gain and loss of function approaches to demonstrate that modulating the extent of initial neonatal fungal colonization affected the extent of BPD-like lung injury in mice. We also identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury. Conclusions These findings demonstrate that features of the initial intestinal fungal microbiome are associated with the later development of BPD in premature neonates and exert a microbiome-driven effect that is transferable and modifiable in murine models, which suggests both causality and a potential therapeutic strategy. Video Abstract |
| format | Article |
| id | doaj-art-8f05104de448424f896c1a846284a912 |
| institution | Kabale University |
| issn | 2049-2618 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj-art-8f05104de448424f896c1a846284a9122025-02-02T12:33:58ZengBMCMicrobiome2049-26182025-01-0113112010.1186/s40168-025-02032-xThe fungal microbiota modulate neonatal oxygen-induced lung injuryIsaac Martin0Mary Silverberg1Ahmed Abdelgawad2Kosuke Tanaka3Brian A. Halloran4Teodora Nicola5Erin D. Myers6Jay P. Desai7Catrina T. White8Ibrahim Karabayir9Oguz Akbilgic10Laura Tipton11Samuel J. Gentle12Namasivayam Ambalavanan13Brian M. Peters14Luan D. Vu15Viral G. Jain16Charitharth V. Lal17Stephania A. Cormier18Joseph F. Pierre19Tamás Jilling20Ajay J. Talati21Kent A. Willis22Division of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamCollege of Medicine, The University of Tennessee Health Science CenterDivision of Neonatology, Department of Pediatrics, College of Medicine, The University of Tennessee Health Science CenterDivision of Neonatology, Department of Pediatrics, College of Medicine, The University of Tennessee Health Science CenterDivision of Cardiology, Department of Medicine, Wake Forest University School of Medicine, Wake Forest UniversityDivision of Cardiology, Department of Medicine, Wake Forest University School of Medicine, Wake Forest UniversityDepartments of Biology and Mathematics & Statistics, James Madison UniversityDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, The University of Tennessee Health Science CenterDepartment of Molecular Microbiology and Immunology, The University of Texas at San AntonioDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDepartment of Biological Sciences, Louisiana State UniversityDepartment of Nutritional Sciences, College of Agricultural and Life Sciences, The University of WI–MadisonDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamDivision of Neonatology, Department of Pediatrics, College of Medicine, The University of Tennessee Health Science CenterDivision of Neonatology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at BirminghamAbstract Background The immature lungs of very preterm infants are exposed to supraphysiologic oxygen, contributing to bronchopulmonary dysplasia (BPD), a chronic lung disease that is the most common morbidity of prematurity. While the microbiota significantly influences neonatal health, the relationship between the intestinal microbiome, particularly micro-eukaryotic members such as fungi and yeast, and lung injury severity in newborns remains unknown. Results Here, we show that the fungal microbiota modulates hyperoxia-induced lung injury severity in very low birth weight premature infants and preclinical pseudohumanized and altered fungal colonization mouse models. Instead of fungal communities dominated by Candida and Saccharomyces, the first stool microbiomes of infants who developed BPD had less interconnected community architectures with a greater diversity of rarer fungi. After using a pseudohumanized model to show that transfer to the neonatal microbiome from infants with BPD increased the severity of lung injury, we used gain and loss of function approaches to demonstrate that modulating the extent of initial neonatal fungal colonization affected the extent of BPD-like lung injury in mice. We also identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury. Conclusions These findings demonstrate that features of the initial intestinal fungal microbiome are associated with the later development of BPD in premature neonates and exert a microbiome-driven effect that is transferable and modifiable in murine models, which suggests both causality and a potential therapeutic strategy. Video Abstracthttps://doi.org/10.1186/s40168-025-02032-xMultikingdom microbiomeGut microbiomeFungal microbiomeMycobiomePreterm infantChronic lung injury |
| spellingShingle | Isaac Martin Mary Silverberg Ahmed Abdelgawad Kosuke Tanaka Brian A. Halloran Teodora Nicola Erin D. Myers Jay P. Desai Catrina T. White Ibrahim Karabayir Oguz Akbilgic Laura Tipton Samuel J. Gentle Namasivayam Ambalavanan Brian M. Peters Luan D. Vu Viral G. Jain Charitharth V. Lal Stephania A. Cormier Joseph F. Pierre Tamás Jilling Ajay J. Talati Kent A. Willis The fungal microbiota modulate neonatal oxygen-induced lung injury Microbiome Multikingdom microbiome Gut microbiome Fungal microbiome Mycobiome Preterm infant Chronic lung injury |
| title | The fungal microbiota modulate neonatal oxygen-induced lung injury |
| title_full | The fungal microbiota modulate neonatal oxygen-induced lung injury |
| title_fullStr | The fungal microbiota modulate neonatal oxygen-induced lung injury |
| title_full_unstemmed | The fungal microbiota modulate neonatal oxygen-induced lung injury |
| title_short | The fungal microbiota modulate neonatal oxygen-induced lung injury |
| title_sort | fungal microbiota modulate neonatal oxygen induced lung injury |
| topic | Multikingdom microbiome Gut microbiome Fungal microbiome Mycobiome Preterm infant Chronic lung injury |
| url | https://doi.org/10.1186/s40168-025-02032-x |
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