Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure

IntroductionAir pollution, particularly environmental tobacco smoke, poses significant health risks, especially to pregnant women and their infants. This study explores the difference in response to cigarette smoke (CS) exposure between pregnant and non-pregnant mice by examining lung transcriptomic...

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Main Authors: Ali Dehghani, Lei Wang, Johan Garssen, Eirini Styla, Thea Leusink-Muis, Ingrid van Ark, Gert Folkerts, Jeroen van Bergenhenegouwen, Saskia Braber
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1590290/full
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author Ali Dehghani
Ali Dehghani
Lei Wang
Lei Wang
Johan Garssen
Johan Garssen
Eirini Styla
Thea Leusink-Muis
Ingrid van Ark
Gert Folkerts
Jeroen van Bergenhenegouwen
Jeroen van Bergenhenegouwen
Saskia Braber
Saskia Braber
author_facet Ali Dehghani
Ali Dehghani
Lei Wang
Lei Wang
Johan Garssen
Johan Garssen
Eirini Styla
Thea Leusink-Muis
Ingrid van Ark
Gert Folkerts
Jeroen van Bergenhenegouwen
Jeroen van Bergenhenegouwen
Saskia Braber
Saskia Braber
author_sort Ali Dehghani
collection DOAJ
description IntroductionAir pollution, particularly environmental tobacco smoke, poses significant health risks, especially to pregnant women and their infants. This study explores the difference in response to cigarette smoke (CS) exposure between pregnant and non-pregnant mice by examining lung transcriptomic profiles, neutrophil numbers, key mediators of neutrophil chemotaxis, and gut microbiota composition. MethodsPregnant and non-pregnant mice were exposed to either air or CS. Bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cells and mediators. RNA sequencing was conducted on lung tissue to identify transcriptomic alterations. Gut microbiota composition and short-chain fatty acid (SCFA) levels were assessed to explore the interactions within the gut-lung axis. ResultsCS exposure resulted in a significant increase in inflammatory cells in the BALF, notably neutrophils, with pregnant dams showing a more substantial increase compared to non-pregnant mice. Transcriptomic analysis revealed neutrophil chemotaxis as the most enriched pathway in CS-exposed pregnant dams. Key genes associated with neutrophil-mediated inflammation, such as CXCL1, S100A8, and S100A9, were significantly upregulated. Gut microbiota analysis showed altered composition and reduced alpha and beta diversity in CS-exposed pregnant dams compared with air-exposed pregnant dams, along with compositional differences between CS-exposed pregnant and non-pregnant mice. CS exposure also resulted in a decrease in cecal SCFA levels in pregnant dams. DiscussionIn conclusion, pregnancy as well as CS exposure induce differences in lung transcriptomic responses which might drive exacerbated lung inflammatory responses measured as neutrophil influx and activity. Microbiota functional and compositional states are also affected by both pregnancy and CS exposure, possibly indicating a gut-lung bidirectional effect.
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spelling doaj-art-e5c50cde3caf4faa85c65504d7d23e342025-08-20T03:59:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.15902901590290Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposureAli Dehghani0Ali Dehghani1Lei Wang2Lei Wang3Johan Garssen4Johan Garssen5Eirini Styla6Thea Leusink-Muis7Ingrid van Ark8Gert Folkerts9Jeroen van Bergenhenegouwen10Jeroen van Bergenhenegouwen11Saskia Braber12Saskia Braber13Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsOutpatient Clinic for Occupational Medicine, Department of Public and Occupational Health, Amsterdam UMC, Amsterdam, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDanone Research and Innovation, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDanone Research and Innovation, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDanone Research and Innovation, Utrecht, NetherlandsIntroductionAir pollution, particularly environmental tobacco smoke, poses significant health risks, especially to pregnant women and their infants. This study explores the difference in response to cigarette smoke (CS) exposure between pregnant and non-pregnant mice by examining lung transcriptomic profiles, neutrophil numbers, key mediators of neutrophil chemotaxis, and gut microbiota composition. MethodsPregnant and non-pregnant mice were exposed to either air or CS. Bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cells and mediators. RNA sequencing was conducted on lung tissue to identify transcriptomic alterations. Gut microbiota composition and short-chain fatty acid (SCFA) levels were assessed to explore the interactions within the gut-lung axis. ResultsCS exposure resulted in a significant increase in inflammatory cells in the BALF, notably neutrophils, with pregnant dams showing a more substantial increase compared to non-pregnant mice. Transcriptomic analysis revealed neutrophil chemotaxis as the most enriched pathway in CS-exposed pregnant dams. Key genes associated with neutrophil-mediated inflammation, such as CXCL1, S100A8, and S100A9, were significantly upregulated. Gut microbiota analysis showed altered composition and reduced alpha and beta diversity in CS-exposed pregnant dams compared with air-exposed pregnant dams, along with compositional differences between CS-exposed pregnant and non-pregnant mice. CS exposure also resulted in a decrease in cecal SCFA levels in pregnant dams. DiscussionIn conclusion, pregnancy as well as CS exposure induce differences in lung transcriptomic responses which might drive exacerbated lung inflammatory responses measured as neutrophil influx and activity. Microbiota functional and compositional states are also affected by both pregnancy and CS exposure, possibly indicating a gut-lung bidirectional effect.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1590290/fullpregnancyair pollutionenvironmental tobacco smokeneutrophil chemotaxisgut microbiotalung transcriptomics
spellingShingle Ali Dehghani
Ali Dehghani
Lei Wang
Lei Wang
Johan Garssen
Johan Garssen
Eirini Styla
Thea Leusink-Muis
Ingrid van Ark
Gert Folkerts
Jeroen van Bergenhenegouwen
Jeroen van Bergenhenegouwen
Saskia Braber
Saskia Braber
Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure
Frontiers in Immunology
pregnancy
air pollution
environmental tobacco smoke
neutrophil chemotaxis
gut microbiota
lung transcriptomics
title Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure
title_full Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure
title_fullStr Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure
title_full_unstemmed Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure
title_short Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure
title_sort pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure
topic pregnancy
air pollution
environmental tobacco smoke
neutrophil chemotaxis
gut microbiota
lung transcriptomics
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1590290/full
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