Du Juan, Zhang Dong, Wang Fengliu, Shang Xuesong, Zhang Jingjia, Wang Guanhua, Ding Jingwen, Ren Aiwu, Jing Shuang, Bai Lu, Liu Ying, Zhao Ye, Li Peng, Yang Shuyi, Liu Jing, Xiang Xuefang, Chen Qiang, Xu Yingchun, Xia Jiang, Yang Qiwen
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Key Laboratory of Pathogen Infection Prevention and Control, Peking Union Medical College, Ministry of Education, Beijing, China.
Front Microbiol. 2025 Apr 29;16:1578820. doi: 10.3389/fmicb.2025.1578820. eCollection 2025.
Plasma microbial cell-free DNA (mcfDNA) is a key biomarker for diagnosing bloodstream infections (BSIs), which contribute significantly to morbidity and mortality, particularly in patients with severe trauma, chronic illnesses, or immunosuppressive conditions. However, the baseline distribution of mcfDNA in different populations remains unclear. This study characterizes plasma mcfDNA profiles across various human populations.
A total of 300 blood samples were collected from 10 groups: healthy individuals (Group A), patients with chronic diseases but no infections (Group B1-B7), patients with mild-to-moderate infections (Group C), and patients meeting sepsis criteria (Group D). Multiplex droplet digital PCR (ddPCR) was used to detect mcfDNA from 10 common sepsis-causing bacterial species, two fungal species, and three herpesviruses (HSV-1, Epstein-Barr virus [EBV], and Cytomegalovirus [CMV]).
Most pathogens in all groups showed low mcfDNA copy concentrations (~100 copies/mL), forming a baseline. Group A had no pathogens exceeding this level, while Group B showed elevated and (10-10 copies/mL). In Group C, 53 pathogens were detected above baseline, with EBV, CMV, and HSV-1 as the most common (copy concentrations 10-10 copies/mL). In Group D, 57 pathogens exceeded baseline, primarily EBV, , , , and CMV. Although statistical analysis showed no significant differences in pathogen distribution between Groups C and D, Gram-negative bacteria were more prevalent in Group D (70% vs. 53.3%, OR = 2.03), while viral pathogens were more frequently detected in Group C (93.3% vs. 76.7%, OR = 0.24). The microbial profiles and mcfDNA copy concentrations in Groups C and D were similar (10-10 copies/mL), distinguishing them from Groups A and B.
This study provides a comprehensive characterization of mcfDNA across different health states, demonstrating the utility of ddPCR in detecting microbial infections. These findings contribute to refining infection diagnostics and improving early detection strategies for BSIs and sepsis.
血浆微生物游离DNA（mcfDNA）是诊断血流感染（BSI）的关键生物标志物，血流感染对发病率和死亡率有显著影响，尤其是在严重创伤、慢性疾病或免疫抑制患者中。然而，mcfDNA在不同人群中的基线分布仍不清楚。本研究对不同人群的血浆mcfDNA特征进行了描述。
从10组人群中总共采集了300份血液样本：健康个体（A组）、患有慢性疾病但无感染的患者（B1 - B7组）、轻至中度感染患者（C组）以及符合脓毒症标准的患者（D组）。采用多重液滴数字PCR（ddPCR）检测来自10种常见的引起脓毒症的细菌、2种真菌和3种疱疹病毒（HSV - 1、爱泼斯坦 - 巴尔病毒[EBV]和巨细胞病毒[CMV]）的mcfDNA。
所有组中的大多数病原体显示出较低的mcfDNA拷贝浓度（约100拷贝/毫升），形成了一个基线。A组没有病原体超过这个水平，而B组显示 和 升高（10 - 10拷贝/毫升）。在C组中，检测到53种病原体高于基线水平，其中EBV、CMV和HSV - 1最为常见（拷贝浓度为10 - 10拷贝/毫升）。在D组中，57种病原体超过基线水平，主要是EBV、 、 、 和CMV。尽管统计分析显示C组和D组之间病原体分布没有显著差异，但革兰氏阴性菌在D组中更为普遍（70%对53.3%，OR = 2.03），而病毒病原体在C组中更频繁地被检测到（93.3%对76.7%，OR =
