Dong Ruifeng, Gu Xiaona, Su Lixia, Wu Qingdong, Tang Yufu, Liang Hongying, Xue Xiangming, Zhang Teng, Zhan Jingming
Key Laboratory of Radiation Environment & Health of the Ministry of Ecology and Environment, China Institute of Radiation Protection, Taiyuan 030006, China.
Shanxi Key Laboratory of Forensic Medicine, School of Forensic Medicine, Shanxi Medical University, Jinzhong 030605, China.
Metabolites. 2025 Jul 22;15(8):492. doi: 10.3390/metabo15080492.
: This study aimed to evaluate the effects of lung injury induced by insoluble uranium oxide particles on gut microbiota and related metabolites in rats. : The rats were randomly divided into six UO dose groups. A rat lung injury model was established through UO aerosol. The levels of uranium in lung tissues were detected by ICP-MS. The expression levels of the inflammatory factors and fibrosis indexes were measured by enzyme-linked immunosorbent assay. Paraffin embedding-based hematoxylin & eosin staining for the lung tissue was performed to observe the histopathological imaging features. Metagenomic sequencing technology and HM700-targeted metabolomics were conducted in lung tissues. : Uranium levels in the lung tissues increased with dose increase. The expression levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Collagen I, and Hydroxyproline (Hyp) in rat lung homogenate increased with dose increase. Inflammatory cell infiltration and the deposition of extracellular matrix were observed in rat lung tissue post-exposure. Compared to the control group, the ratio of and in the gut microbiota decreased, the relative abundance of decreased, and the relative abundance of increased. The important differential metabolites mainly include αlpha-linolenic acid, gamma-linolenic acid, 2-Hydroxybutyric acid, Beta-Alanine, Maleic acid, Hyocholic acid, L-Lysine, L-Methionine, L-Leucine, which were mainly concentrated in unsaturated fatty acid biosynthesis, propionic acid metabolism, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, and other pathways in the UO group compared to the control group. : These findings suggest that uranium-induced lung injury can cause the disturbance of gut microbiota and its metabolites in rats, and these changes are mainly caused by and , focusing on unsaturated fatty acid biosynthesis and the propionic acid metabolism pathway.
本研究旨在评估不溶性氧化铀颗粒诱导的肺损伤对大鼠肠道微生物群及相关代谢产物的影响。将大鼠随机分为六个氧化铀剂量组。通过氧化铀气溶胶建立大鼠肺损伤模型。采用电感耦合等离子体质谱法检测肺组织中的铀含量。通过酶联免疫吸附测定法检测炎症因子和纤维化指标的表达水平。对肺组织进行基于石蜡包埋的苏木精-伊红染色，以观察组织病理学成像特征。对肺组织进行宏基因组测序技术和靶向HM700代谢组学分析。肺组织中的铀含量随剂量增加而升高。大鼠肺匀浆中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、I型胶原和羟脯氨酸（Hyp）的表达水平随剂量增加而升高。暴露后大鼠肺组织中观察到炎症细胞浸润和细胞外基质沉积。与对照组相比，肠道微生物群中拟杆菌属和梭菌属的比例降低，双歧杆菌属的相对丰度降低，肠球菌属的相对丰度增加。重要的差异代谢产物主要包括α-亚麻酸、γ-亚麻酸、2-羟基丁酸、β-丙氨酸、马来酸、猪去氧胆酸、L-赖氨酸、L-蛋氨酸、L-亮氨酸，与对照组相比，这些代谢产物在氧化铀组中主要集中在不饱和脂肪酸生物合成、丙酸代谢、氨酰-tRNA生物合成、苯丙氨酸代谢等途径中。这些研究结果表明，铀诱导的肺损伤可导致大鼠肠道微生物群及其代谢产物紊乱，这些变化主要由拟杆菌属和梭菌属引起，重点关注不饱和脂肪酸生物合成和丙酸代谢途径。
