Multi-omics analyses of airway host–microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions

Zhengzheng Yan, Boxuan Chen, Yuqiong Yang, Xinzhu Yi, Mingyuan Wei, Gertrude Ecklu-Mensah, Mary M. Buschmann, Haiyue Liu, Jingyuan Gao, Weijie Liang, Xiaomin Liu, Junhao Yang, Wei Ma, Zhenyu Liang, Fengyan Wang, Dandan Chen, Lingwei Wang, Weijuan Shi, Martin R. Stampfli, Pan LiShenhai Gong, Xia Chen, Wensheng Shu, Emad M. El-Omar, Jack A. Gilbert, Martin J. Blaser, Hongwei Zhou, Rongchang Chen, Zhang Wang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe–host interactions in COPD through an in-depth profiling of the sputum metagenome, metabolome, host transcriptome and proteome from 99 patients with COPD and 36 healthy individuals in China. Multi-omics data were integrated using sequential mediation analysis, to assess in silico associations of the microbiome with two primary COPD inflammatory endotypes, neutrophilic or eosinophilic inflammation, mediated through microbial metabolic interaction with host gene expression. Hypotheses of microbiome–metabolite–host interaction were identified by leveraging microbial genetic information and established metabolite–human gene pairs. A prominent hypothesis for neutrophil-predominant COPD was altered tryptophan metabolism in airway lactobacilli associated with reduced indole-3-acetic acid (IAA), which was in turn linked to perturbed host interleukin-22 signalling and epithelial cell apoptosis pathways. In vivo and in vitro studies showed that airway microbiome-derived IAA mitigates neutrophilic inflammation, apoptosis, emphysema and lung function decline, via macrophage–epithelial cell cross-talk mediated by interleukin-22. Intranasal inoculation of two airway lactobacilli restored IAA and recapitulated its protective effects in mice. These findings provide the rationale for therapeutically targeting microbe–host interaction in COPD.

Original languageEnglish (US)
Pages (from-to)1361-1375
Number of pages15
JournalNature Microbiology
Issue number9
StatePublished - Sep 2022

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology


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