ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1590290
This article is part of the Research TopicMucosal Microbiota Immunomodulation of the Gut-Lung AxisView all 7 articles
Pregnancy exacerbates neutrophil responses in murine lungs and alters gut microbiota composition after cigarette smoke exposure
Provisionally accepted
Ali DehghaniLei Wang
Johan GarssenEirini Styla
Thea Leusink-Muis
Ingrid Van Ark
Gert Folkerts
Jeroen Van Bergenhenegouwen
Saskia Braber*- Utrecht University, Utrecht, Netherlands
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Air 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. Pregnant 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. CS 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 nonpregnant mice. CS exposure also resulted in a decrease in cecal SCFA levels in pregnant dams.In 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.
Keywords: Pregnancy, Air Pollution, Environmental tobacco smoke, Neutrophil chemotaxis, Gut Microbiota, Lung Transcriptomics
Received: 09 Mar 2025; Accepted: 22 Jul 2025.
Copyright: © 2025 Dehghani, Wang, Garssen, Styla, Leusink-Muis, Ark, Folkerts, Van Bergenhenegouwen and Braber. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Saskia Braber, Utrecht University, Utrecht, Netherlands
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