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Background <p>Blood testing aids pneumonia diagnosis, but its effectiveness varies. Given the invasiveness of bronchoalveolar lavage fluid (BALF) sampling versus blood testing’s simplicity, this study investigates when blood can reliably substitute for BALF in detecting microbial presence, especially for pathogens.</p> Results <p>Metagenomic sequencing was performed on paired BALF-blood samples from 21 post-HSCT immunocompromised (ICP) and 21 immunocompetent (ICT) patients. The ICP cohort was expanded to 62 for biomarker validation. Host responses were profiled via metatranscriptomics (30 BALF samples). Microbial alpha and beta diversity differed significantly between blood and BALF in ICP, but not ICT, patients. ICP patients’ BALF contained a greater diversity and abundance of microbes. A higher proportion of microbial DNA sequences in ICP patients’ blood was also present in their BALF, suggesting a potentially more permeable alveolar-capillary barrier. Related genes (e.g., NABA CORE MATRISOME, extracellular matrix organization, cell-cell adhesion) were downregulated. Upregulated pathways like VEGFA-VEGFR2 signaling and Rho GTPases suggested increased vascular permeability. In ICP patients, 419 microbial sequences in blood indicated their presence in the lower respiratory tract with &gt; 70% certainty.</p> Conclusion <p>Host immune status significantly influences blood-BALF microbial diversity differences. Shared blood-BALF microbial DNA sequences show potential for aiding pneumonia pathogen diagnosis, offering a novel biomarker identification approach.</p>

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Microbial DNA analysis of paired blood-bronchoalveolar lavage fluid in post-HSCT patients with pneumonia implying application conditions of blood as a surrogate in pathogen detection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月18日

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  • Ruiqi Li,
  • Xiangyan He,
  • Zhonglin Chen,
  • Jie Shao,
  • Jiangzhou Feng,
  • Liping Wan,
  • Mengyuan Zhang,
  • Jun Yang,
  • Yin Tong,
  • Baoxia Dong,
  • Chongmei Huang,
  • Huiying Qiu,
  • Yu Cai,
  • Jiahua Niu,
  • Xiaowei Xu,
  • Xianming Song,
  • Jinmin Ma,
  • Hongfeng Ge,
  • Kun Zhou

摘要

Background

Blood testing aids pneumonia diagnosis, but its effectiveness varies. Given the invasiveness of bronchoalveolar lavage fluid (BALF) sampling versus blood testing’s simplicity, this study investigates when blood can reliably substitute for BALF in detecting microbial presence, especially for pathogens.

Results

Metagenomic sequencing was performed on paired BALF-blood samples from 21 post-HSCT immunocompromised (ICP) and 21 immunocompetent (ICT) patients. The ICP cohort was expanded to 62 for biomarker validation. Host responses were profiled via metatranscriptomics (30 BALF samples). Microbial alpha and beta diversity differed significantly between blood and BALF in ICP, but not ICT, patients. ICP patients’ BALF contained a greater diversity and abundance of microbes. A higher proportion of microbial DNA sequences in ICP patients’ blood was also present in their BALF, suggesting a potentially more permeable alveolar-capillary barrier. Related genes (e.g., NABA CORE MATRISOME, extracellular matrix organization, cell-cell adhesion) were downregulated. Upregulated pathways like VEGFA-VEGFR2 signaling and Rho GTPases suggested increased vascular permeability. In ICP patients, 419 microbial sequences in blood indicated their presence in the lower respiratory tract with > 70% certainty.

Conclusion

Host immune status significantly influences blood-BALF microbial diversity differences. Shared blood-BALF microbial DNA sequences show potential for aiding pneumonia pathogen diagnosis, offering a novel biomarker identification approach.