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

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

  • Nat Microbiol. 2022 Sep;7(9):1361-1375. doi: 10.1038/s41564-022-01196-8.
Zhengzheng Yan  # 1 2,  Boxuan Chen  # 1,  Yuqiong Yang  # 3,  Xinzhu Yi  # 1,  Mingyuan Wei  # 1,  Gertrude Ecklu-Mensah 4,  Mary M Buschmann 4,  Haiyue Liu 5,  Jingyuan Gao 1,  Weijie Liang 1,  Xiaomin Liu 1,  Junhao Yang 1,  Wei Ma 6,  Zhenyu Liang 3,  Fengyan Wang 3,  Dandan Chen 7,  Lingwei Wang 7,  Weijuan Shi 3,  Martin R Stampfli 8,  Pan Li 9,  Shenhai Gong 10,  Xia Chen 11,  Wensheng Shu 1,  Emad M El-Omar 9,  Jack A Gilbert 4,  Martin J Blaser 12,  Hongwei Zhou 13,  Rongchang Chen 14,  Zhang Wang 15
Affiliations

Affiliations

  • 1 Institute of Ecological Sciences, South China Normal University, Guangzhou, China.
  • 2 Department of Anesthesiology, Nanfang Hospital, Guangdong Provincial Key Laboratory of Proteomics, Southern Medical University, Guangzhou, China.
  • 3 First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, Guangzhou, China.
  • 4 Department of Pediatrics, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA.
  • 5 Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, China.
  • 6 Institute of Statistics and Big Data, Renmin University of China, Beijing, China.
  • 7 Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, China.
  • 8 Department of Medicine, Firestone Institute of Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
  • 9 Microbiome Research Centre, St. George and Sutherland Clinical School, UNSW, Sydney, New South Wales, Australia.
  • 10 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
  • 11 Department of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan, China.
  • 12 Center for Advanced Biotechnology and Medicine, Rutgers University, New Brunswick, NJ, USA.
  • 13 Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China. hzhou@smu.edu.cn.
  • 14 Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, China. chenrc@vip.163.com.
  • 15 Institute of Ecological Sciences, South China Normal University, Guangzhou, China. wangz@m.scnu.edu.cn.
  • # Contributed equally.
PMID: 35995842 DOI: 10.1038/s41564-022-01196-8
Abstract

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.

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