School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.
School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
Chem Biol Interact. 2021 Aug 1;344:109496. doi: 10.1016/j.cbi.2021.109496. Epub 2021 May 1.
An increased risk of developing lung cancer has been associated with exposure to cigarette smoke carcinogens and alteration in the gut microbiota. However, there is limited understanding about the impact of exposure to NNK and BaP, the two important components of cigarette smoke carcinogens, on gut microbiota in lung cancer. The present study characterized the influence of exposure to a mixture of NNK plus BaP on lung cancer, feces metabolite composition, and gut microbiota in the A/J mice. The A/J mice were administered NNK plus BaP, and the changes in gut microbiota and feces metabolic profiles were characterized using 16S rRNA gene sequencing and metabolomics, respectively. Results presented here illustrated that a mixture of NNK plus BaP exposure triggered lung carcinogenesis as shown by light microscopy and histopathological evaluation. 16S rRNA sequencing of gut microbiota indicated that exposure to NNK plus BaP could modified fecal bacterial composition. Elevated levels of Actinobacteria, Bifidobacterium, and Intestinimonas and reduced levels of Alistipes, Odoribacter, and Acetatifactor are associated with NNK plus BaP triggered lung cancer. In addition, metabolomics profile revealed the regulation of metabolism including purine metabolism, phenylalanine metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and others. In conclusion, the results provide some guidance for using gut microbes as biomarkers to assess the progression of lung cancer, and lead to interventional targets to control the development of the disease in the future.
接触香烟烟雾致癌物和肠道微生物群改变与肺癌发生风险增加有关。然而，对于接触香烟烟雾致癌物中两种重要成分 NNK 和 BaP 对肺癌肠道微生物群的影响，人们的了解有限。本研究描述了暴露于 NNK 和 BaP 混合物对 A/J 小鼠肺癌、粪便代谢产物组成和肠道微生物群的影响。通过 16S rRNA 基因测序和代谢组学，分别对 NNK 和 BaP 混合物暴露后肠道微生物群和粪便代谢谱的变化进行了表征。这里呈现的结果表明，NNK 和 BaP 混合物暴露会引发肺癌，这可通过光学显微镜和组织病理学评估来证明。肠道微生物群的 16S rRNA 测序表明，NNK 和 BaP 暴露可改变粪便细菌组成。厚壁菌门、双歧杆菌和 Intestinimonas 的水平升高，而拟杆菌门、Odoribacter 和 Acetatifactor 的水平降低与 NNK 和 BaP 引发的肺癌有关。此外，代谢组学分析揭示了代谢的调节，包括嘌呤代谢、苯丙氨酸代谢、初级胆汁酸生物合成、甾体激素生物合成、不饱和脂肪酸生物合成、亚油酸代谢等。总之，这些结果为将肠道微生物群作为评估肺癌进展的生物标志物提供了一些指导，并为未来控制疾病发展提供了干预靶点。
