NHC Key Laboratory of Pneumoconiosis, Shanxi Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, China.
Quality Control Office, Xishan Occupational Disease Prevention and Control Institute, Taiyuan, China.
Microbiol Spectr. 2024 Nov 5;12(11):e0004924. doi: 10.1128/spectrum.00049-24. Epub 2024 Sep 16.
Coal workers' pneumoconiosis (CWP) is a severe occupational disease resulting from prolonged exposure to coal dust. However, its pathogenesis remains elusive, compounded by a lack of early detection markers and effective treatments. Although the impact of gut microbiota on lung diseases is acknowledged, its specific role in CWP is unclear. This study aims to explore changes in the gut microbiome and metabolome in CWP, while also assessing the correlation between gut microbes and alterations in lung function. Fecal specimens from 43 CWP patients and 48 dust-exposed workers (DEW) were examined using 16S rRNA gene sequencing for microbiota and liquid chromatography-mass spectrometry for metabolite profiling. We observed similar gut microbial α-diversity but significant differences in flora composition (β-diversity) between patients with CWP and the DEW group. After adjusting for age using multifactorial linear regression analysis (MaAsLin2), the distinct gut microbiome profile in CWP patients revealed an increased presence of pro-inflammatory microorganisms such as and . Furthermore, in CWP patients, alterations in gut microbiota-particularly reduced α-diversity and changes in microbial composition-were significantly correlated with impaired pulmonary function, a relationship not observed in DEW. This underscores the specific impact of gut microbiota on pulmonary health in individuals with CWP. Metabolomic analysis of fecal samples from CWP patients and DEW identified 218 differential metabolites between the two groups, with a predominant increase in metabolites in CWP patients, suggesting enhanced metabolic activity in CWP. Key altered metabolites included various lipids, amino acids, and organic compounds, with silibinin emerging as a potential biomarker. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis linked these metabolites to pathways relevant to the development of pulmonary fibrosis. Additionally, studies on the interaction between microbiota and metabolites showed positive correlations between certain bacteria and increased metabolites in CWP, further elucidating the complex interplay in this disease state. Our findings suggest a potential contributory role of gut microbiota in CWP pathogenesis through metabolic regulation, with implications for diagnostic biomarkers and understanding disease mechanisms, warranting further molecular investigation.
The findings have significant implications for the early diagnosis and treatment of coal workers' pneumoconiosis, highlighting the potential of gut microbiota as diagnostic biomarkers. They pave the way for new research into gut microbiota-based therapeutic strategies, potentially focusing on modifying gut microbiota to mitigate disease progression.
本研究旨在探讨 CWP 患者肠道微生物群和代谢组的变化,并评估肠道微生物与肺功能改变的相关性。
采用 16S rRNA 基因测序技术对 43 例 CWP 患者和 48 例尘暴露工人(DEW)的粪便标本进行微生物群落分析,采用液相色谱-质谱联用技术进行代谢组学分析。
我们观察到 CWP 患者和 DEW 组的肠道微生物 α 多样性相似,但菌群组成(β 多样性)存在显著差异。通过多因素线性回归分析(MaAsLin2)调整年龄因素后,CWP 患者肠道微生物群的独特特征显示,促炎微生物如 和 的丰度增加。此外,在 CWP 患者中,肠道微生物群的改变,特别是 α 多样性降低和微生物组成的变化,与肺功能受损显著相关,而在 DEW 中未观察到这种关系。这突显了肠道微生物群对 CWP 患者肺部健康的特定影响。对 CWP 患者和 DEW 的粪便样本进行代谢组学分析,发现两组之间有 218 个差异代谢物,CWP 患者的代谢物明显增加,提示 CWP 患者的代谢活性增强。关键的改变代谢物包括各种脂质、氨基酸和有机化合物,其中水飞蓟素作为一种潜在的生物标志物出现。京都基因与基因组百科全书通路富集分析将这些代谢物与与肺纤维化发展相关的途径联系起来。此外,对微生物群和代谢物相互作用的研究表明,某些细菌与 CWP 中增加的代谢物之间存在正相关,进一步阐明了这种疾病状态下的复杂相互作用。
这些发现表明,肠道微生物群可能通过代谢调节在 CWP 发病机制中发挥作用,为诊断生物标志物和理解疾病机制提供了新的见解,值得进一步进行分子研究。