汉防己甲素治疗后煤工尘肺患者肠道菌群的变化特征  

Changes in intestinal flora of coal workers'pneumoconiosis patients after tetrandrine intervention

作　　者：刘晓璐 李宝平 沈福海 孙治平 赵永梅[5] 侯博文 高丽妮 李倩倩 李欣宇 马超逸 LIU Xiaolu;LI Baoping;SHEN Fuhai;SUN Zhiping;ZHAO Yongmei;HOU Bowen;GAO Lini;LI Qianqian;LI Xinyu;MA Chaoyi(School of Public Health,North China University of Technology,Tangshan,Hebei 063210,China;Hebei Key Laboratory of Occupational Health and Safety for Coal Industry,North China University of Technology,Tangshan,Hebei 063210,China;Occupational Disease Department,Emergency General Hospital,Beijing 100028,China;The First Hospital of Shanxi Medical University,National Health Commission Key Laboratory of Pneumoconiosis,Shanxi,Taiyuan 030001,China;Department of Occupational Health,Centre for Disease Control and Prevention,Chaoyang District,Beijing 100021,China)

机构地区：[1]华北理工大学公共卫生学院,河北唐山063210 [2]华北理工大学河北省煤矿卫生与安全重点实验室,河北唐山063210 [3]应急总医院职业病科,北京100028 [4]山西医科大学第一医院国家卫生健康委员会尘肺病重点实验室,山西太原030001 [5]北京市朝阳区疾病预防控制中心职业卫生科,北京100021

出　　处：《环境与职业医学》2024年第6期625-631,共7页Journal of Environmental and Occupational Medicine

基　　金：国家卫生健康委员会尘肺病重点实验室开放课题基金资助项目(NHC202305)。

摘　　要：[背景]尘肺病是目前我国广泛存在的职业病,作为肺部疾病的一种,其病理损害主要为肺部不可逆的纤维化改变。目前有多项研究显示,煤工尘肺等肺部疾病的发生、发展与肠道菌群有密切的联系。[目的]基于16SrDNA高通量测序结果,观察煤工尘肺患者的肠道菌群特征及服用汉防己甲素(粉防己碱)治疗后肠道菌群的变化。[方法]于2023年4—7月,纳入就诊于应急总医院职业病科门诊共80例煤工尘肺患者。所有患者均服用汉防己甲素片治疗4周。同期设健康对照24例。汉防己甲素片治疗前为A组,治疗后为B组,健康人群为C组。治疗前后分别收集粪便样本,利用16SrDNA高通量测序技术基于V3-V4平台,检测患者治疗后的肠道菌群变化。[结果]治疗前A组、治疗后B组与健康人群C组对比发现门水平及属水平优势菌群相同,治疗后B组与健康人群C组中拟杆菌门、双歧杆菌属、拟杆菌属及粪杆菌属相对丰度均高于治疗前A组,放线菌门、布劳特氏菌属及罗姆布次菌属相对丰度均低于治疗前A组(均P<0.05)。健康人群C组在梭菌属、巨单胞菌属及乳杆菌属的相对丰度上均低于治疗前A组与治疗后B组,差异均有统计学意义(P<0.05)。Alpha多样性分析示:A组Chao1指数高于C组(P<0.01)。与治疗前A组相比:治疗后B组Shannon指数均升高,壹期患者中Simpson指数升高差异均有统计学意义(P<0.05),Chao1指数差异无统计学意义(P>0.05);贰期和叁期患者Chao1指数、Shannon指数、Simpson指数值差异均无统计学意义(P>0.05)。Beta多样性分析显示:煤工尘肺A组与健康人群C组间菌群结构差异有统计学意义(P<0.05);不同分期治疗前后菌群结构差异均有统计学意义(P<0.05)。偏正交最小二乘法分析(PLS-DA)显示A组与C组、治疗前后A组与B组存在明显的组间差异。LEfSe分析显示治疗后在壹期、贰期和叁期中发现对差异贡献显著标志物基本一致,主要为[Background]Pneumoconiosis is a widespread occupational disease in China at present.As a type of lung diseases,its pathological damage is mainly irreversible fibrotic changes in the lungs.Several studies have shown that the occurrence and development of lung diseases such as coal workers'pneumoconiosis are closely related to intestinal flora.[Objective]To observe intestinal flora of coal workers'pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets.[Methods]A total of 80 patients with coal workers'pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled.All patients were treated with tetrandrine tablets for 4 weeks,with group A before the treatment of tetrandrine tablets and group B after the treatment.In the same period,24 healthy controls(group C)were set up.Stool samples were collected before and after the treatment.Using 16SrDNA high-throughput sequencing,gene V3-V4 sequencing technology,and bioinformatic analysis platform,we evaluated the intestinal flora after treatment by groups.[Results]The dominant flora at the phylum level and genus level were the same across three groups.The relative abundances of phylum Bacteroidetes,Bifidobacterium,Bacteroides,and Facealibacterium in groups B and C were higher than those in group A,and the relative abundances of phy-lum Actinobacteria,genus Blautia,and genus Romboutsia in groups B and C were lower than those in group A(P<0.05).The relative abundances of genus Clostridium,genus Megamonas,and genus Lactobacillus in group C was lower than that in groups A and B(P<0.05).The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C(P<0.01).Compared with group A,the Shannon index was higher in group B,and the increases of Simpson index were all statistically significant in stage I patients(P<0.05),but the differences in Chao

关 键 词：尘肺病 煤工尘肺 肠道菌群 16SrDNA基因测序 汉防己甲素片 

分 类 号：R135.2[医药卫生—劳动卫生]