Article Text

Download PDFPDF
Original research
Faecal microbial transfer and complex carbohydrates mediate protection against COPD
  1. Kurtis F Budden1,
  2. Shakti D Shukla1,
  3. Kate L Bowerman2,
  4. Annalicia Vaughan3,4,5,6,
  5. Shaan L Gellatly1,
  6. David L A Wood2,
  7. Nancy Lachner2,
  8. Sobia Idrees3,4,
  9. Saima Firdous Rehman1,3,4,
  10. Alen Faiz7,
  11. Vyoma K Patel3,4,
  12. Chantal Donovan1,4,
  13. Charlotte A Alemao1,
  14. Sj Shen3,4,
  15. Nadia Amorim3,4,
  16. Rajib Majumder3,4,
  17. Kanth S Vanka1,
  18. Jazz Mason1,
  19. Tatt Jhong Haw1,
  20. Bree Tillet8,
  21. Michael Fricker1,
  22. Simon Keely1,
  23. Nicole Hansbro3,4,
  24. Gabrielle T Belz8,
  25. Jay Horvat1,
  26. Thomas Ashhurst9,10,
  27. Caryn van Vreden9,11,
  28. Helen McGuire11,
  29. Barbara Fazekas de St Groth11,
  30. Nicholas J C King9,10,11,12,
  31. Ben Crossett13,
  32. Stuart J Cordwell13,14,
  33. Lorenzo Bonaguro15,16,
  34. Joachim L Schultze15,16,17,
  35. Emma E Hamilton‐Williams8,
  36. Elizabeth Mann18,
  37. Samuel C Forster19,
  38. Matthew A Cooper20,
  39. Leopoldo N Segal21,
  40. Sanjay H Chotirmall22,
  41. Peter Collins23,24,
  42. Rayleen Bowman5,6,
  43. Kwun M Fong5,6,
  44. Ian A Yang5,6,
  45. Peter A B Wark1,
  46. Paul G Dennis25,
  47. Philip Hugenholtz2,
  48. Philip M Hansbro1,3,4
  1. 1Priority Research Centre for Healthy Lungs and Immune Health Research Program, The University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia
  2. 2School of Chemistry and Molecular Biosciences, Australian Centre for Ecogenomics, The University of Queensland, Brisbane, QLD, Australia
  3. 3Centre for Inflammation, Centenary Institute, Sydney, NSW, Australia
  4. 4School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia
  5. 5UQ Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
  6. 6Department of Thoracic Medicine, The Prince Charles Hospital, Chermside, QLD, Australia
  7. 7Respiratory Bioinformatics and Molecular Biology, School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia
  8. 8Frazer Institute, University of Queensland, Woolloongabba, QLD, Australia
  9. 9Sydney Cytometry, Charles Perkins Centre, Centenary Institute and The University of Sydney, Sydney, NSW, Australia
  10. 10Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, Australia
  11. 11Ramaciotti Facility for Human Systems Biology, Charles Perkins Centre and The University of Sydney, Sydney, NSW, Australia
  12. 12Discipline of Pathology, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia
  13. 13Sydney Mass Spectrometry, The University of Sydney, Sydney, NSW, Australia
  14. 14School of Life and Environmental Sciences, Charles Perkins Centre and The University of Sydney, Sydney, NSW, Australia
  15. 15Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
  16. 16Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
  17. 17PRECISE Platform for Single Cell Genomics and Epigenomics, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) and the University of Bonn, Bonn, Germany
  18. 18Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK
  19. 19Centre for Innate Immunity and Infectious Diseases and Department of Molecular and Translational Science, Hudson Institute of Medical Research and Monash University, Melbourne, VIC, Australia
  20. 20Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  21. 21Division of Pulmonary and Critical Care Medicine, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA
  22. 22Lee Kong Chian School of Medicine, Translational Respiratory Research Laboratory, Singapore
  23. 23Mater Research Institute, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
  24. 24Department of Dietetics & Food Services, Mater Hospital, Brisbane, QLD, Australia
  25. 25School of Earth and Environmental Sciences, The University of Queensland, Brisbane, QLD, Australia
  1. Correspondence to Professor Philip M Hansbro, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia; Philip.Hansbro{at}uts.edu.au

Abstract

Objective Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear.

Design Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation.

Results FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes.

Conclusion The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

  • COLONIC MICROFLORA
  • BASIC SCIENCES
  • DIETARY FIBRE
  • IMMUNOLOGY
  • INFLAMMATORY DISEASES

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. Shotgun metagenomics sequencing data for the microbiome of mice have been deposited in the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/) under accession number PRJNA740117 (https://dataview.ncbi.nlm.nih.gov/object/PRJNA740117?reviewer=f8tgn1h6vsiqrfpnpiqt1r61i6) and may be re-used with appropriate acknowledgement. Raw data not included there can be obtained with the consent of the corresponding author.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. Shotgun metagenomics sequencing data for the microbiome of mice have been deposited in the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/) under accession number PRJNA740117 (https://dataview.ncbi.nlm.nih.gov/object/PRJNA740117?reviewer=f8tgn1h6vsiqrfpnpiqt1r61i6) and may be re-used with appropriate acknowledgement. Raw data not included there can be obtained with the consent of the corresponding author.

View Full Text

Footnotes

  • KFB, SDS and KLB are joint first authors.

  • Twitter @KurtisBudden, @sjsijieshen, @nadiamorim, @simonkeely

  • KFB, SDS and KLB contributed equally.

  • Contributors KFB, SDS, KLB, SLG, NGH, AV, TJH, EEH-W, EM, KMF, IAY, PH and PMH designed the study. KFB, SDS, SLG, SFR, CD, BT, NA, RM, CAA, KSV, JM, MF, TA, CvV, HMG and AV performed experiments. KFB, SDS, SLG, NL, KSV and JM processed samples. KFB, SDS, KLB, SLG, DLAW, SI, VKP, AF, SFR, SS, KSV, TA, BC, SJC, LB, JLS, TA, BFdSG, NJCK and AV analysed the data. KFB, SDS, KLB, AV, TJH, LNS, SHC, IAY, SCF, PABW, PH and PMH interpreted the results. KFB, SDS, KLB, SI and AV prepared the manuscript. PMH is the guarantor for this paper. All authors edited and reviewed the manuscript.

  • Funding This work and PMH were supported by grants and fellowships from the National Health and Medical Research Council (NHMRC) of Australia (1059238, 1079187, 1175134), the Rainbow Foundation, Australian Research Council (110101107), Cancer Council of NSW, University of Newcastle and University of Technology Sydney and The Prince Charles Hospital Foundation (RF2017-05, INN2018-30). JLS was supported by German Research Foundation (DFG) under Germany’s Excellence Strategy (EXC2151-390873048) as well as under SFB 1454 (432325352), the BMBF-funded excellence project Diet–Body–Brain (DietBB), EU grant under Horizon 2020 DiscovAir (874656) and the EU project SYSCID (733100).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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

  • 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.