METHODS: We collected 16 protected specimen brush (PSB) and 8 broncho-alveolar lavage (BAL) samples from 8 iatrogenic subglottic tracheal stenosis patients, including 8 PSB samples from tracheal scar sites, 8 PSB samples from scar-free sites and 8 BAL samples, by lavaging the subsegmental bronchi of the right-middle lobe. Metagenomic sequencing was performed to characterize the microbiome profiling of 16 PSB and 8 BAL samples. Untargeted metabolomics was performed in 6 PSB samples (3 from tracheal scar PSB and 3 from tracheal scar-free PSB) using high-performance liquid chromatography‒mass spectrometry (LC‒MS).
RESULTS: At the species level, the top four bacterial species were Neisseria subflava, Streptococcus oralis, Capnocytophaga gingivals, and Haemophilus aegyptius. The alpha and beta diversity among tracheal scar PSB, scar-free PSB and BAL samples were compared, and no significant differences were found. Untargeted metabolomics was performed in 6 PSB samples using LC‒MS, and only one statistically significant metabolite, carnitine, was identified. Pathway enrichment analysis of carnitine revealed significant enrichment in fatty acid oxidation.
CONCLUSIONS: Our study found that carnitine levels in tracheal scar tissue were significantly lower than those in scar-free tissue, which might be a new target for the prevention and treatment of iatrogenic tracheal stenosis in the future.
方法:我们从8例医源性声门下气管狭窄患者中收集了16例受保护的样本刷(PSB)和8例支气管肺泡灌洗(BAL)样本,包括来自气管疤痕部位的8个PSB样本,8个来自无疤痕部位的PSB样本和8个BAL样本,通过灌洗右中叶的亚段支气管。进行宏基因组测序以表征16个PSB和8个BAL样品的微生物组谱。使用高效液相色谱-质谱(LC-MS)对6个PSB样品(3个来自气管瘢痕PSB,3个来自气管无瘢痕PSB)进行了非靶向代谢组学研究。
结果:在物种层面,前四种细菌是亚黄奈瑟菌,口链球菌,Capnocytophagagingival,和埃及嗜血杆菌.气管瘢痕PSB之间的α和β多样性,比较无疤痕的PSB和BAL样本,没有发现显著差异。使用LC-MS在6个PSB样品中进行了非靶向代谢组学,只有一种具有统计学意义的代谢物,肉碱,已确定。肉碱的途径富集分析揭示了脂肪酸氧化的显着富集。
结论:我们的研究发现,气管瘢痕组织中的肉碱水平明显低于无瘢痕组织,可能成为今后医源性气管狭窄防治的新靶点。