Yang-Jensen Sune K, Näegele Nora, Sonne Si Brask, Koeninger Louis, Pineault Marie, Tremblay Félix, Kristensen Nanna Ny, Bay Lene, Aubin Sophie, Morissette Mathieu C, Jensen Benjamin A H
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Human Health, Novonesis A/S, Lyngby, Denmark.
Gut Microbes. 2025 Dec;17(1):2519699. doi: 10.1080/19490976.2025.2519699. Epub 2025 Jun 29.
The gut microbiota has been implicated in numerous aspects of host health and immune regulation. Specifically, recent studies have linked gut microbes to the pathogenesis of chronic obstructive pulmonary disease (COPD), primarily induced by excessive cigarette smoke, although the underlying mechanisms remain elusive. Here, we investigated the role of gastrointestinal (GI) host-microbe interactions on pulmonary health. Using two distinct means of modulating GI host-microbe relations, we dissected how gut microbes fuel pulmonary inflammation in mouse models of cigarette smoke (CS)-induced lung disease. We found that CS caused profound changes to the colonic mucosa, with reduced mucus and increased bacterial encroachment. Modulating host-microbe interactions using antibiotics and recombinant human β-defensin 2 restricted colonic bacterial encroachment, limiting interactions between host and microbe. These strategies resulted in substantial ~50% decrease in pulmonary neutrophil infiltration following both acute and chronic exposure to CS. The reported findings provide additional evidence of a gut-lung axis, offering novel insight into the role of the gut microbiota in pulmonary immune activation, which could represent a novel avenue for future therapeutic strategies.
肠道微生物群与宿主健康和免疫调节的许多方面都有关联。具体而言，最近的研究已将肠道微生物与慢性阻塞性肺疾病（COPD）的发病机制联系起来，COPD主要由过度吸烟引起，但其潜在机制仍不清楚。在此，我们研究了胃肠道（GI）宿主-微生物相互作用对肺部健康的作用。我们使用两种不同的方法来调节GI宿主-微生物关系，剖析了在香烟烟雾（CS）诱导的肺部疾病小鼠模型中肠道微生物如何加剧肺部炎症。我们发现，CS导致结肠黏膜发生深刻变化，黏液减少，细菌侵袭增加。使用抗生素和重组人β-防御素2调节宿主-微生物相互作用可限制结肠细菌侵袭，减少宿主与微生物之间的相互作用。这些策略导致在急性和慢性暴露于CS后，肺部中性粒细胞浸润大幅减少约50%。这些研究结果为肠-肺轴提供了更多证据，为肠道微生物群在肺部免疫激活中的作用提供了新的见解，这可能代表了未来治疗策略的新途径。
