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Original research
Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide
  1. Hsin-Chih Lai1,2,3,4,5,
  2. Tzu-Lung Lin1,
  3. Ting-Wen Chen6,7,8,
  4. Yu-Lun Kuo9,
  5. Chih-Jung Chang3,
  6. Tsung-Ru Wu10,
  7. Ching-Chung Shu11,
  8. Ying-Huang Tsai3,
  9. Simon Swift12,
  10. Chia-Chen Lu13,14
  1. 1Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  2. 2Microbiota Research Center and Emerging Viral Infections Research Center, Chang Gung University, Taoyuan, Taiwan
  3. 3Central Research Laboratory, Xiamen Chang Gung Hospital, XiaMen, China
  4. 4Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
  5. 5Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
  6. 6Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan
  7. 7Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
  8. 8Center For Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Chiao Tung University, Hsinchu, Taiwan
  9. 9Biotools, Co, Ltd, New Taipei City, Taiwan
  10. 10Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan
  11. 11Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  12. 12Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand
  13. 13Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan
  14. 14Department of Chest Medicine, Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan
  1. Correspondence to Dr Chia-Chen Lu, Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan; chiachen.lulu{at}gmail.com

Abstract

Objective Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.

Design A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.

Results Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.

Conclusion The gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

  • intestinal microbiology
  • immunology

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Footnotes

  • H-CL and T-LL contributed equally.

  • Correction notice This article has been corrected since it published Online First. Figures 4 and 6 have been updated.

  • Contributors T-LL conceived the project, contributed to experimental design, performed experiments, interpreted the results, prepared the figures and wrote the manuscript; T-WC performed the scRNAseq analysis; Y-LK performed the microbiota analysis; C-JC and T-RW contributed to experimental design and performed experiments; C-CS, Y-HT and SS reviewed and edited the manuscript; H-CL and C-CL conceived and supervised the project, interpreted the results and wrote the manuscript; all authors discussed the results and approved the manuscript.

  • Funding This study was funded by CORPD1F0013 and CORPD1J0052 from Chang Gung Memorial Hospital, 108–2321-B-182–002, 109–2320-B-030–010, 109–2327-B-182–001 from Ministry of Science and Technology (MOST), Microbiota Research CenterCentre from Chang Gung University, and the Research CenterCentre for Emerging Viral Infections from The Featured Areas Research CenterCentre ProgramProgramme within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan and MOST, Taiwan (MOST109-3017-F-182–001).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Animal experiments were approved by the Institutional Animal Care and Use Protocol of Fu Jen Catholic University and were performed according to their guidelines (animal ethics approval numbers A10558 and A10849).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. The data that support the findings of this study are available from the corresponding author, on reasonable request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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