病原宏基因组高通量测序用于成人肺部感染诊断的探讨

doi:10.3969/j.issn.1673-8640.2026.03.002

摘要/Abstract

摘要：

近年来，病原宏基因组高通量测序（mNGS）技术在感染性疾病，特别是肺部感染中的研究和应用发展迅速，在传统技术不易检测的少见病原体肺部感染的诊断中发挥了积极作用。然而，mNGS技术本身仍存在局限性，阳性阈值标准不统一，易出现念珠菌、结核分枝杆菌和耶氏肺孢子菌结果误判的情况。文章从微生物诊断管理角度探讨mNGS技术的研究方向及其发展。

关键词: 病原宏基因组高通量测序, 肺部感染, 微生物诊断管理

Abstract:

In recent years，metagenomic next-generation sequencing （mNGS）technology has developed rapidly in the research and application of infectious diseases，especially in pulmonary infections. It has played a positive role in the diagnosis of infections caused by rare pathogens that are difficult to determine by traditional methods. However，the mNGS technology still has limitations that need to be overcome. The positive threshold standards are not unified，and there are misjudgements in the determination of Candida，Mycobacterium tuberculosis and Pneumocystis jiroveci. This review focuses on the research direction and development of mNGS technology from the perspective of microbial diagnosis management.

Key words: Metagenomic next-generation sequencing, Pulmonary infection, Microbial diagnosis management

中图分类号:

R446.7

何礼贤. 病原宏基因组高通量测序用于成人肺部感染诊断的探讨[J]. 检验医学, 2026, 41(3): 217-222.

HE Lixian. Discussion on the application of high-throughput metagenomic sequencing of pathogens in the diagnosis of pulmonary infections in adults[J]. Laboratory Medicine, 2026, 41(3): 217-222.

参考文献 54

[1]	PALACIOS G, DRUCE J, DU L, et al. A new arenavirus in a cluster of fatal transplant-associated diseases[J]. N Engl J Med, 2008, 358(10):991-998. DOI URL
[2]	WILSON M R, NACCACHE S N, SAMAYOA E, et al. Actionable diagnosis of neuroleptospirosis by nextgeneration sequencing[J]. N Engl J Med, 2014, 370(25):2408-2417. DOI URL
[3]	WU F, ZHAO S, YU B, et al. A new coronavirus associated with human respiratory disease in China[J]. Nature, 2020,579:265-269.
[4]	HE S, WEI J, FENG J, et al. The application of metagenomic next-generation sequencing in pathogen diagnosis:a bibliometric analysis based on Web of Science[J]. Front Cell Infect Microbiol, 2023, 13:1112229.
[5]	DIAO Z, HAN D, ZHANG R, et al. Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections[J]. J Adv Res, 2021, 38:201-212. DOI URL
[6]	ZHANG Z, TIAN L. Validation of mNGS results using extensive lab and clinical data[J]. BMC Microbiol, 2025, 25(1):173. DOI PMID
[7]	QIAN Y Y, WANG H Y, ZHOU Y, et al. Improving pulmonary infection diagnosis with metagenomic next generation sequencing[J]. Front Cell Infect Microbiol, 2021, 10:567615.
[8]	WENSEL C R, PLUZNICK J L, SALZBERG S L, et al. Next-generation sequencing:insights to advance clinical investigations of the microbiome[J]. J Clin Invest, 2022, 132(7):e154944. DOI URL
[9]	BLAUWKAMP T A, THAIR S, ROSEN M J, et al. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease[J]. Nat Microbiol, 2019, 4(4):663-674. DOI PMID
[10]	CHEN H, YIN Y, GAO H, et al. Clinical utility of in-house metagenomic next-generation sequencing for the diagnosis of lower respiratory tract infections and analysis of the host immune response[J]. Clin Infect Dis, 2020, 71(suppl 4):S416-S426. DOI PMID
[11]	WU X, LI Y, ZHANG M, et al. Etiology of severe community-acquired pneumonia in adults based on metagenomic next-generation sequencing:a prospective multicenter study[J]. Infect Dis Ther, 2020, 9(4):1003-1015. DOI
[12]	LIANG W, ZHANG Q, QIAN Q, et al. Diagnostic strategy of metagenomic nextgeneration sequencing for gram negative bacteria in respiratory infections[J]. Ann Clin Microbiol Antimicrob, 2024, 23(1):10 DOI
[13]	FANG X, MEI Q, FAN X, et al. Diagnostic value of metagenomic next-generation sequencing for the detection of pathogens in bronchoalveolar lavage fluid in ventilator-associated pneumonia patients[J]. Front Microbiol, 2020, 11:599756.
[14]	XIE G, ZHAO B, WANG X, et al. Exploring the clinical utility of metagenomic next-generation sequencing in the diagnosis of pulmonary infection[J]. Infect Dis Ther, 2021, 10(3):1419-1435. DOI PMID
[15]	FANG X, MEI Q, FAN X, et al. Diagnostic value of metagenomic next-generation sequencing for the detection of pathogens in bronchoalveolar lavage ffuid in ventilator-associated pneumonia patients[J]. Front Microbiol, 2020, 11:599756.
[16]	LIN T, TU X, ZHAO J, et al. Microbiological diagnostic performance of metagenomic next-generation sequencing compared with conventional culture for patients with community-acquired pneumonia[J]. Front Cell Infect Microbiol, 2023, 13:1136588.
[17]	陆思芬, 周永召, 王刚, 等. 基于宏基因组二代测序技术的840例疑似肺部感染患者下呼吸道微生物特征分析[J]. 中国呼吸与危重监护杂志, 2022, 21(6):403-411.
[18]	CHAI S, WANG C, LIU Y, et al. Distribution patterns of pathogens causing lower respiratory tract infection based on metagenomic next-generation sequencing[J]. Infec Drug Resist, 2023, 16:6635-6645. DOI URL
[19]	HAO J, LI W, WANG Y, et al. Clinical utility of metagenomic next-generation sequencing in pathogen detection for lower respiratory tract infections and impact on clinical outcomes in southernmost China[J]. Front Cell Infect Microbiol, 2023, 13:1271952.
[20]	WANG J Z, YUAN D, YANG X H, et al. Etiology of lower respiratory tract in pneumonia based on metagenomic next-generation sequencing:a retrospective study[J]. Front Cell Infect Microbiol, 2024, 13:1291980.
[21]	ZHAO Y, MAO R, ZHONG Y, et al. Application of metagenomic next-generation sequencing in pathogen detection for patients with lower respiratory tract infections caused by multidrug-resistant organisms and analysis of related factors[J]. Acta Microbiol Immunol Hung, 2024, 71(4):273-279. DOI URL
[22]	GAO Q, LI L, SU T, et al. A single-center,retrospective study of hospitalized patients with lower respiratory tract infections:clinical assessment of metagenomic next-generation sequencing and identiffcation of risk factors in patients[J]. Respir Res, 2024, 25(1):250. DOI
[23]	LIU M, ZHANG H, LI L, et al. The etiological diagnostic value of metagenomic next-generation sequencing in suspected community-acquired pneumonia[J]. BMC Infect Dis, 2024, 24(1):626. DOI PMID
[24]	ZHOU P, ZHANG D, FU J, et al. Evaluation of different sampling methods combined with metagenomic next-generation sequencing of respiratory specimens in etiological diagnosis of patients with severe pneumonia[J]. Infec Drug Resist, 2024, 17:5729-5738. DOI URL
[25]	ZHAO J, SUN Y, TANG J, et al. The clinical application of metagenomic next-generation sequencing in immunocompromised patients with severe respiratory infections in the ICU[J]. Respir Res, 2024, 25(1):360. DOI
[26]	CHEN H, HUANG Q, WU W, et al. Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections[J]. Eur J Med Res, 2024, 29(1):213. DOI PMID
[27]	MENG B, LIU H, WU Q, et al. Antimicrobial strategies of lower respiratory tract infections in immunocompromised patients based on metagenomic nextgeneration sequencing:a retrospective study[J]. BMC Infec Dis, 2025, 25(1):360. DOI
[28]	ZHENG H, PENG P, WANG S, et al. Microbiological diagnostic performance and clinical effect of metagenomic next-generation sequencing for the detection of immunocompromised patients with community-acquired pneumonia[J]. Infec Drug Resist, 2025,18:1223-1236.
[29]	WANG C, YIN X, MA W, et al. Clinical application of bronchoalveolar lavage ffuid metagenomics next-generation sequencing in cancer patients with severe pneumonia[J]. Respir Res, 2024, 25(1):68. DOI
[30]	JIANG L, HAN L, ZHONG Y, et al. High utility of bronchoalveolar lavage ffuid metagenomic next-generation sequencing approach for etiological diagnosis of pneumonia[J]. BMC Infect Dis, 2024, 24(1):1232. DOI
[31]	HU X, JIANG L, LIU X, et al. The diagnostic value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in critically ill patients with respiratory tract infections[J]. Microbiol Spectr, 2024, 12(8):e0045824. DOI URL
[32]	ZHENG Y, LIU W, XIAO T, et al. Clinical utility of metagenomic next-generation sequencing on bronchoalveolar lavage fluid in diagnosis of lower respiratory tract infections[J]. BMC Pul Med, 2024, 24(1):422.
[33]	中国成人念珠菌病诊断与治疗专家共识组. 中国成人念珠菌病诊断与治疗专家共识[J]. 中华内科杂志, 2020, 59(1):5-17.
[34]	世界华人医学真菌专业委员会. 侵袭性肺真菌病诊断路径专家共识(2024版)[J]. 中华检验医学杂志, 2025, 48(4):459-468.
[35]	CORNELY O A, SPRUTE R, BASSETTI M, et al. Global guideline for the diagnosis and management of candidiasis:an initiative of the ECMM in cooperation with ISHAM and ASM[J]. Lancet infect Dis, 2025, 25(12):e684.
[36]	冯耘. mNGS在抗合成酶综合征合并间质性肺病诊治中的应用[EB/OL].[2024-05-07](2025-05-06).https://www.rccrc.cn/article/1703.
[37]	WU D, WANG W, XUN Q, et al. Metagenomic next-generation sequencing indicates more precise pathogens in patients with pulmonary infection:a retrospective study[J]. Front Cell Infect Microbiol, 2022, 12:977591.
[38]	JIN X, LI J, SHAO M, et al. Improving suspected pulmonary infection diagnosis by bronchoalveolar lavage fluid metagenomic next-generation sequencing:a multicenter retrospective study[J]. Microbiol Spectr, 2022, 10(4):e0247321. DOI URL
[39]	HAO J, LI W, WANG Y, et al. Clinical utility of metagenomic next-generation sequencing in pathogen detection for lower respiratory tract infections and impact on clinical outcomes in southernmost China[J]. Front Cell Infect Microbiol, 2023, 13:1271952.
[40]	LAI Y, CHEN B, CHEN S, et al. Experience of implementing metagenomic next-generation sequencing in patients with suspected pulmonary infection in clinical practice[J]. Sci Rep, 2025, 15(1):9579. DOI
[41]	PETO L, NADJM B, HORBY P, et al. The bacterial aetiology of adult community-acquired pneumonia in Asia:a systematic review[J]. Trans R Soc Trop Med Hyg, 2014, 108(6):326-337. DOI URL
[42]	QIN T, ZHOU H, REN H, et al. Incidence,etiology,and environmental risk factors of community-acquired pneumonia requiring hospitalization in China:a 3-year,prospective,age-stratified,multicenter case-control study[J]. Open Forum Infect Dis, 2021, 8(11):ofab499.
[43]	YOU Y, NI Y M, SHI G. Diagnostic accuracy of metagenomic next-generation sequencing in pulmonary tuberculosis:a systematic review and meta-analysis[J]. Syst Rev, 2024, 13(1):317. DOI
[44]	ZHOU H, LARKIN P M K, ZHAO D, et al. Clinical impact of metagenomic next-generation sequencing of bronchoalveolar lavage in the diagnosis and management of pneumonia. A multicenter prospective observational study[J]. J Mol Diag, 2021, 23(10):1259-1268. DOI URL
[45]	MIAO Q, MA Y, WANG Q, et al. Microbiological diagnostic performance of metagenomic next-generation sequencing when applied to clinical practice[J]. Clin Infect Dis, 2018, 67(suppl 2):S231-S240.
[46]	ZHOU X, WU H, RUAN Q, et al. Clinical evaluation of diagnosis efficacy of active Mycobacterium tuberculosis complex infection via metagenomic next-generation sequencing of direct clinical samples[J]. Front Cell Infect Microbiol, 2019, 9:351. DOI URL
[47]	TEKIN A, TRUONG H H, ROVATI L, et al. The diagnostic accuracy of metagenomic next-generation sequencing in diagnosing Pneumocystis pneumonia:a systemic review and meta-analysis[J]. Open Forum Infect Dis, 2023, 10(9):ofad442.
[48]	XING F, DENG C, LUO Z, et al. Rapid diagnosis of Pneumocystis jirovecii pneumonia and respiratory tract colonization by next generation sequencing[J]. Mycopathologia, 2024, 189(3):38. DOI
[49]	CAÑAS-ARBOLEDA A, HERNÁNDEZ-FLÓREZ C, JAVIER G, et al. Colonization by Pneumocystis jirovecii in patients with chronic obstructive pulmonary disease:association with exacerbations and lung function status[J]. Braz J Infect Dis, 2019, 23(5):352-357. DOI URL
[50]	MOHAMMADI-GHALEHBIN B, HABIBZADEH S, ARZANLOU M, et al. Colonization of Pneumocystis jirovecii in patients who received and not received corticosteroids admitted to the intensive care unit:airborne transmission approach[J]. Iran J Pathol, 2018, 13(2):136-143. DOI URL
[51]	FATEMI Y, BERGL P A. Diagnostic stewardshiop:appropriate testing and judicious treastments[J]. Crit Care Clin, 2022, 38(1):69-87. DOI URL
[52]	FABRE V, DAVIS A, DIEKEMA D J, et al. Principles of diagnostic stewardship:a practical guide from the society for healthcare epidemiology of america diagnostic stewardship task force[J]. Infect Control Hosp Epidemiol, 2023, 44(2):178-185. DOI URL
[53]	北京协和医院, 国家卫健委临床检验中心, 中国食品药品检定研究院, 临床实验室检测和体外诊断系统病原宏基因组学高通量测序的性能确认[Z].
[54]	WU X, SUN T, HE H, et al. Effect of metagenomic next-generation sequencing on clinical outcomes of patients with severe community-acquired pneumonia in ICU:a multicenter randomized controlled trial[J]. Chest, 2025, 167(2):362-373. DOI URL