Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands.
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
Int J Mol Sci. 2024 Apr 5;25(7):4058. doi: 10.3390/ijms25074058.
Chronic obstructive pulmonary disease (COPD) patients and smokers have a higher incidence of intestinal disorders. The aim of this study was to gain insight into the transcriptomic changes in the lungs and intestines, and the fecal microbial composition after cigarette smoke exposure. Mice were exposed to cigarette smoke and their lung and ileum tissues were analyzed by RNA sequencing. The top 15 differentially expressed genes were investigated in publicly available gene expression datasets of COPD and Crohn's disease (CD) patients. The murine microbiota composition was determined by 16S rRNA sequencing. Increased expression of MMP12, GPNMB, CTSK, CD68, SPP1, CCL22, and ITGAX was found in the lungs of cigarette smoke-exposed mice and COPD patients. Changes in the intestinal expression of CD79B, PAX5, and FCRLA were observed in the ileum of cigarette smoke-exposed mice and CD patients. Furthermore, inflammatory cytokine profiles and adhesion molecules in both the lungs and intestines of cigarette smoke-exposed mice were profoundly changed. An altered intestinal microbiota composition and a reduction in bacterial diversity was observed in cigarette smoke-exposed mice. Altered gene expression in the murine lung was detected after cigarette smoke exposure, which might simulate COPD-like alterations. The transcriptomic changes in the intestine of cigarette smoke-exposed mice had some similarities with those of CD patients and were associated with changes in the intestinal microbiome. Future research could benefit from investigating the specific mechanisms underlying the observed gene expression changes due to cigarette smoke exposure, focusing on identifying potential therapeutic targets for COPD and CD.
慢性阻塞性肺疾病（COPD）患者和吸烟者的肠道疾病发病率较高。本研究旨在深入了解吸烟暴露后肺部和肠道的转录组变化以及粪便微生物组成。将小鼠暴露于香烟烟雾中，并通过 RNA 测序分析其肺部和回肠组织。在 COPD 和克罗恩病（CD）患者的公开基因表达数据集调查了前 15 个差异表达基因。通过 16S rRNA 测序确定了鼠微生物群组成。在香烟烟雾暴露的小鼠肺部和 COPD 患者中发现 MMP12、GPNMB、CTSK、CD68、SPP1、CCL22 和 ITGAX 的表达增加。在香烟烟雾暴露的小鼠回肠中观察到 CD79B、PAX5 和 FCRLA 的肠道表达变化。此外，香烟烟雾暴露的小鼠肺部和肠道的炎症细胞因子谱和粘附分子发生了深刻变化。观察到香烟烟雾暴露的小鼠肠道微生物群组成发生改变，细菌多样性降低。在香烟烟雾暴露后，在小鼠肺部检测到改变的基因表达，这可能模拟 COPD 样改变。香烟烟雾暴露的小鼠肠道的转录组变化与 CD 患者的变化有些相似，与肠道微生物组的变化有关。未来的研究可以从研究由于香烟烟雾暴露而观察到的基因表达变化的具体机制中受益，重点是确定 COPD 和 CD 的潜在治疗靶点。
