南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (1): 146-155.doi: 10.12122/j.issn.1673-4254.2024.01.17

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基于16S rRNA测序分析阻塞性睡眠呼吸暂停患者肠道靶标菌群的变化

朱继伟，卢曼路，焦倩倩，孙运良，刘 璐，丁红红，于 燕，潘 磊   

  1. 滨州医学院附属医院呼吸与危重症医学科，山东 滨州 256603
  • 发布日期:2024-01-24

Analysis of gut target microbiota and species difference in patients with obstructive sleep apnea based on 16S rRNA sequencing

ZHU Jiwei, LU Manlu, JIAO Qianqian, SUN Yunliang, LIU Lu, DING Honghong, YU Yan, PAN Lei   

  1. Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou 256603, China
  • Published:2024-01-24

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摘要： 目的 分析阻塞性睡眠呼吸暂停（OSA）患者和健康人群肠道菌群的差异，探讨肠道菌群在OSA发病中的作用及意义。方法 随机纳入2022年1月~12月就诊于本院诊断为OSA的患者39例作为OSA组，健康志愿者20例作为对照组。收集两组人群的粪便标本，通过16S rRNA高通量测序分析其微生物组成，分析两组人群肠道菌群之间的Alpha多样性、Beta多样性、物种差异与标志物种和差异生物功能代谢通路功能预测分析。结果 Alpha多样性分析显示，OSA组的物种多样性指数Shannon和Simpson、物种丰度指数Observed species及菌群均匀度指数Pielou 均低于对照组（P<0.05）；Beta多样性分析显示，两组间群落结构存在差异（P<0.05）。OSA组肠道菌群群落结构上与对照组存在差异，潜在致病菌属如假单胞菌属、巨单胞菌属等菌群丰度增加（P<0.05）。LEfSe分析结果显示，与对照组相比，OSA组假单胞菌属、巨单胞菌属、梭杆菌属丰度升高（P<0.05）。关联网络分析结果显示，影响宿主稳态的为差异标志菌群；随机森林分析和ROC曲线结果显示，假单胞菌属是具有重要鉴别意义的生物标志菌属。差异代谢通路预测功能显示，维持肠道菌群稳态起主要作用功能的是生物合成功能，假单胞菌属参与了芳香族生物胺降解和酮葡萄糖酸代谢。结论 OSA患者存在肠道菌群紊乱，肠菌中假单胞菌属可能通过参与物质代谢影响OSA发生发展，可望作为防治OSA的潜在肠菌靶标。

关键词: 阻塞性睡眠呼吸暂停；肠道菌群；16S rRNA；多样性；高通量测序

Abstract: Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea (OSA) and healthy individuals and the role of gut microbiota in the pathogenesis of OSA. Methods Thirty-nine patients with OSA admitted to our hospital between May and December, 2022 and 20 healthy individuals were enrolled in this study. Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high- throughput sequencing analysis. The alpha diversity, beta diversity, and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed. Results The species diversity (Shannon and Simpson) indexes, richness (observed species) and evenness (Pielou) of gut microbiota were significantly lower in OSA patients than in the healthy individuals (P<0.05). The OSA patients had also a significantly lowered community diversity (P<0.05) with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes (P<0.05). LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas, Meganomonas, and Fusobacterium (P<0.05). The differential marker flora affected host homeostasis. Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis. Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis, and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway. Conclusion OSA patients have obvious gut microbiota disturbances, and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Key words: obstructive sleep apnea; gut microbiota; 16S rRNA; diversity; high-throughput sequencing