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<p>Chronic obstructive pulmonary disease (COPD) remains a major health burden with few effective therapies, particularly for emphysema. The gut–lung axis and microbial metabolites, such as short-chain fatty acids (SCFAs), have emerged as modulators of lung inflammation. We investigated the therapeutic effects of <i>Lactobacillus fermentum</i> HEM20792 (LF), identified through a colon mimetic personalized pharmaceutical meta-analytical screening (PMAS) platform using fecal samples from severe COPD patients. LF and <i>Lactobacillus sakei</i> HEM20224 (LS) were orally administered to smoke-exposed mice, followed by lung function testing, histopathology, RNA sequencing, single-cell transcriptomics, and fecal microbiome/SCFAs analyses. LF attenuated emphysematous changes, improved compliance, and reduced macrophage and IL-17+ lymphocyte infiltration. Single-cell analysis showed restoration of alveolar macrophages and reduction of pathogenic C1q<sup>+</sup> macrophages, while transcriptomics revealed normalization of NF-κB and arachidonic acid pathways and attenuation of IL-17– and SPP1-associated signaling. LF also increased fecal SCFAs levels. These findings provide preclinical evidence for LF as a promising microbiome-based therapeutic candidate for COPD.</p>

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A colon mimetic screening approach reveals Lactobacillus fermentum as a microbiome-based therapy for COPD

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月14日

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  • Na Hyun Kim,
  • Jaeik Oh,
  • Jang Ho Lee,
  • Sunyoung Lee,
  • Eun Sung Jung,
  • Dong Ho Suh,
  • Hye-Ji Kang,
  • Bobae Kim,
  • Hye-Shin Kim,
  • Hae Rim Jung,
  • Heeseo Kim,
  • I Na Rae Yun,
  • Yosep Ji,
  • Sung-Yup Cho,
  • Sei Won Lee

摘要

Chronic obstructive pulmonary disease (COPD) remains a major health burden with few effective therapies, particularly for emphysema. The gut–lung axis and microbial metabolites, such as short-chain fatty acids (SCFAs), have emerged as modulators of lung inflammation. We investigated the therapeutic effects of Lactobacillus fermentum HEM20792 (LF), identified through a colon mimetic personalized pharmaceutical meta-analytical screening (PMAS) platform using fecal samples from severe COPD patients. LF and Lactobacillus sakei HEM20224 (LS) were orally administered to smoke-exposed mice, followed by lung function testing, histopathology, RNA sequencing, single-cell transcriptomics, and fecal microbiome/SCFAs analyses. LF attenuated emphysematous changes, improved compliance, and reduced macrophage and IL-17+ lymphocyte infiltration. Single-cell analysis showed restoration of alveolar macrophages and reduction of pathogenic C1q+ macrophages, while transcriptomics revealed normalization of NF-κB and arachidonic acid pathways and attenuation of IL-17– and SPP1-associated signaling. LF also increased fecal SCFAs levels. These findings provide preclinical evidence for LF as a promising microbiome-based therapeutic candidate for COPD.