Skip to main content

Advertisement

SpringerLink
Log in

Gut–lung Microbiota Interactions in Chronic Obstructive Pulmonary Disease (COPD): Potential Mechanisms Driving Progression to COPD and Epidemiological Data

  • COPD
  • Published:
Lung Aims and scope Submit manuscript

Abstract

This paper focuses on the gut–lung axis in the context of Inflammatory Bowel Disease (IBD) and Chronic Obstructive Pulmonary Disease (COPD), highlighting the key role played by microbial dysbiosis and the impact of environmental and genetic factors on the innate and acquired immune system and on chronic inflammation in the intestinal and pulmonary tracts. Recent evidence indicates that Antigen-Presenting Cells (APCs) perform regulatory activity influencing the composition of the microbiota. APCs (macrophages, dendritic cells, B cells) possess membrane receptors known as Pattern Recognition Receptors (PRRs), a category of toll-like receptors (TLRs). PRRs recognise distinct microbial structures and microbial metabolites called Signals, which modulate the saprophytic microbial equilibrium of the healthy microbiota by recognising molecular profiles associated with commensal microbes (Microbe-Associated Molecular Patterns, MAMPs). During dysbiosis, pathogenic bacteria can prompt an inflammatory response, producing PAMPs (Pathogen-Associated Molecular Patterns) thereby activating the proliferation of inflammatory response cells, both local and systemic. This series of regulatory and immune-response events is responsible (together with chronic infection, incorrect diet, obesity, etc.) for the systemic chronic inflammation (SCI) known as “low-grade inflammation” typical of COPD and IBD. This review looks at immunological research and explores the role of the microbiota, looking at two recent clinical studies, SPIROMICS and AERIS. There is a need for further clinical studies to characterize the pulmonary microbiota and to obtain new information about the pathogenesis of lung disease to improve our knowledge and treatment strategies and identify new therapeutic targets.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Black H, Mendoza M, Murin S (2007) Thoracic manifestations of inflammatory bowel disease. Chest 131(2):524–532. https://doi.org/10.1378/chest.06-1074

    Article  PubMed  Google Scholar 

  2. Global Initiative for Chronic Obstructive Lung Disease (GOLD). http://www.goldcopd.org. Accessed 2021

  3. Vutcovici M, Bitton A, Ernst P, Kezouh A, Suissa S, Brassard P (2016) Inflammatory bowel disease and risk of mortality in COPD. Eur Respir J 47:1357–1364. https://doi.org/10.1183/13993003.01945-2015

    Article  PubMed  Google Scholar 

  4. Raj AA, Birring SS, Green R, Grant A, de Caestecker J, Pavord ID (2008) Prevalence of inflammatory bowel disease in patients with airways disease. Respir Med 102(5):780–785. https://doi.org/10.1016/j.rmed.2007.08.014

    Article  PubMed  CAS  Google Scholar 

  5. Labarca G, Drake L, Horta G, Jantz MA, Mehta HJ, Fernandez-Bussy S, Folch E, Majid A, Picco M (2019) Association between inflammatory bowel disease and chronic obstructive pulmonary disease: a systematic review and meta analysis. BMC Pulm Med. https://doi.org/10.1186/s12890-019-0963-y

    Article  PubMed  PubMed Central  Google Scholar 

  6. Brassard P, Vutcovici M, Ernst P, Patenaude V, Sewitch M, Suissa S, Bitton A (2015) Increased incidence of inflammatory bowel disease in Québec residents with airway diseases. Eur Respir J 45(4):962–968. https://doi.org/10.1183/09031936.00079414

    Article  PubMed  Google Scholar 

  7. Lee J, Im JP, Han K, Park S, Soh H, Choi K, Kim J, Chun J, Kim JS (2019) Risk of inflammatory bowel disease in patients with chronic obstructive pulmonary disease: a nationwide, population-based study. World J Gastroenterol 25(42):6354–6364. https://doi.org/10.3748/wjg.v25.i42.6354

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chiu YC, Lee SW, Liu CW, Lan TY, Wu LS (2022) Relationship between gut microbiota and lung function decline in patients with chronic obstructive pulmonary disease: a 1-year follow-up study. Respir Res. https://doi.org/10.1186/s12931-022-01928-8

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chunxi L, Haiyue L, Yanxia L, Jianbing P, Jin S (2020) The gut microbiota and respiratory diseases: new evidence. J Immunol Res 2020:2340670. https://doi.org/10.1155/2020/2340670

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Ekbom A, Brandt L, Granath F, Löfdahl CG, Egesten A (2008) Increased risk of both ulcerative colitis and Crohn’s disease in a population suffering from COPD. Lung 186(3):167–172. https://doi.org/10.1007/s00408-008-9080-z

    Article  PubMed  Google Scholar 

  11. Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, Belzer C, Delgado Palacio S, Arboleya Montes S, Mancabelli L, Lugli GA, Rodriguez JM, Bode L, de Vos W, Gueimonde M, Margolles A, van Sinderen D, Ventura M (2017) The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev. https://doi.org/10.1128/MMBR.00036-17

    Article  PubMed  PubMed Central  Google Scholar 

  12. Girosi D, Bellodi S, Sabatini F, Rossi GA (2006) The lung and the gut: common origins, close links. Paediatr Respir Rev 7(Suppl 1):S235–S239. https://doi.org/10.1016/j.prrv.2006.04.192

    Article  PubMed  Google Scholar 

  13. Raftery AL, Tsantikos E, Harris NL, Hibbs ML (2020) Links between inflammatory bowel disease and chronic obstructive pulmonary disease. Front Immunol. https://doi.org/10.3389/fimmu.2020.02144

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kanner RE, Anthonisen NR, Connett JE (2001) Lower respiratory illnesses promote FEV 1 decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study. Am J RespirCrit Care Med 164(3):358–364. https://doi.org/10.1164/ajrccm.164.3.2010017

    Article  CAS  Google Scholar 

  15. Vestbo J, Prescott E, Lange P (1996) Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. copenhagen city heart study group. Am J Respir Crit Care Med 153(5):1530–1535. https://doi.org/10.1164/ajrccm.153.5.8630597

    Article  PubMed  CAS  Google Scholar 

  16. Turek EM, Cox MJ, Hunter M, Hui J, James P, Willis-Owen SAG, Cuthbertson L, James A, Musk AW, Moffatt MF, Cookson WOCM (2021) Airway microbial communities, smoking and asthma in a general population sample. EBioMedicine 71:103538. https://doi.org/10.1016/j.ebiom.2021.103538

    Article  PubMed  PubMed Central  Google Scholar 

  17. Enaud R, Prevel R, Ciarlo E, Beaufils F, Wieërs G, Guery B, Delhaes L (2020) The gut-lung axis in health and respiratory diseases: a place for inter-organ and inter-kingdom crosstalks. Front Cell Infect Microbiol 10(9):2020. https://doi.org/10.3389/fcimb.2020.00009

    Article  CAS  Google Scholar 

  18. Dumas A, Bernard L, Poquet Y, Lugo-Villarino G, Neyrolles O (2018) The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases. Cell Microbiol 20(12):e12966. https://doi.org/10.1111/cmi.12966

    Article  PubMed  CAS  Google Scholar 

  19. Slack E, Hapfelmeier S, Stecher B, Velykoredko Y, Stoel M, Lawson MA, Geuking MB, Beutler B, Tedder TF, Hardt WD, Bercik P, Verdu EF, McCoy KD, Macpherson AJ (2009) Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. Science 325(5940):617–620. https://doi.org/10.1126/science.1172747

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kuhn KA, Stappenbeck TS (2013) Peripheral education of the immune system by the colonic microbiota. Semin Immunol 25(5):364–369. https://doi.org/10.1016/j.smim.2013.10.002

    Article  PubMed  CAS  Google Scholar 

  21. Borger JG, Lau M, Hibbs ML (2019) The influence of innate lymphoid cells and unconventional T cells in chronic inflammatory lung disease. Front Immunol 10(1597):2019. https://doi.org/10.3389/fimmu.2019.01597

    Article  CAS  Google Scholar 

  22. Abels ER, Breakefield XO (2016) Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol 36(3):301–312. https://doi.org/10.1007/s10571-016-0366-z

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Lawson C, Vicencio JM, Yellon D, Davidson SM (2016) Microvesicles and exosomes: new players in metabolicand cardiovascular disease. J Endocrinol 228(2):R57-71. https://doi.org/10.1530/JOE-15-0201

    Article  PubMed  Google Scholar 

  24. Parkin J, Cohen B (2001) An overview of the immune system. Lancet 357(9270):1777–1789. https://doi.org/10.1016/S0140-6736(00)04904-7

    Article  PubMed  CAS  Google Scholar 

  25. Dommett R, Zilbauer M, George JT, Bajaj-Elliott M (2005) Innate immune defence in the human gastrointestinal tract. Mol Immunol 42(8):903–912. https://doi.org/10.1016/j.molimm.2004.12.004

    Article  PubMed  CAS  Google Scholar 

  26. Gorjifard S, Goldszmid RS (2016) Microbiota-myeloid cell crosstalk beyond the gut. J Leukoc Biol 100(5):865–879. https://doi.org/10.1189/jlb.3RI0516-222R

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Gourbal B, Pinaud S, Beckers GJM, Van Der Meer JWM, Conrath U, Netea MG (2018) Innate immune memory: an evolutionary perspective. Immunol Rev 283(1):21–40. https://doi.org/10.1111/imr.12647

    Article  PubMed  CAS  Google Scholar 

  28. McCoy KD, Burkhard R, Geuking MB (2019) The microbiome and immune memory formation. Immunol Cell Biol 97(7):625–635. https://doi.org/10.1111/imcb.12273

    Article  PubMed  CAS  Google Scholar 

  29. Budden KF, Shukla SD, Rehman SF, Bowerman KL, Keely S, Hugenholtz P, Armstrong-James DPH, Adcock IM, Chotirmall SH, Chung KF, Hansbro PM (2019) Functional effects of the microbiota in chronic respiratory disease. Lancet Respir Med 7(10):907–920. https://doi.org/10.1016/S2213-2600(18)30510-1

    Article  PubMed  Google Scholar 

  30. Guo MY, Chen HK, Ying HZ, Qiu FS, Wu JQ (2021) The role of respiratory flora in the pathogenesis of chronic respiratory diseases. Biomed Res Int. https://doi.org/10.1155/2021/6431862

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sulaiman I, Wu BG, Li Y, Tsay JC, Sauthoff M, Scott AS, Ji K, Koralov SB, Weiden M, Clemente JC, Jones D, Huang YJ, Stringer KA, Zhang L, Geber A, Banakis S, Tipton L, Ghedin E, Segal LN (2021) Functional lower airways genomic profiling of the microbiome to capture active microbial metabolism. Eur Respir J. https://doi.org/10.1183/13993003.03434-2020

    Article  PubMed  PubMed Central  Google Scholar 

  32. Magryś A (2021) Microbiota: a missing link in the pathogenesis of chronic lung inflammatory diseases. Pol J Microbiol 70(1):25–32. https://doi.org/10.33073/pjm-2021-013

    Article  PubMed  PubMed Central  Google Scholar 

  33. Pickard JM, Zeng MY, Caruso R, Núñez G (2017) Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev 279(1):70–89. https://doi.org/10.1111/imr.12567

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Sekirov I, Russell SL, Antunes CM, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev 90(3):859–904. https://doi.org/10.1152/physrev.00045.2009

    Article  PubMed  CAS  Google Scholar 

  35. McGuckin MA, Linden SK, Sutton P, Florin TH (2011) Mucin dynamics and enteric pathogens. Nat Rev Microbiol 9(4):265–278. https://doi.org/10.1038/nrmicro2538

    Article  PubMed  CAS  Google Scholar 

  36. Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3(9):710–720. https://doi.org/10.1038/nri1180

    Article  PubMed  CAS  Google Scholar 

  37. Satoh-Takayama N, Kato T, Motomura Y, Kageyama T, Taguchi-Atarashi N, Kinoshita-Daitoku R, Kuroda E, Di Santo JP, Mimuro H, Moro K, Ohno H (2020) Bacteria-induced group 2 innate lymphoid cells in the stomach provide immune protection through induction of IgA. Immunity 52(4):635-649.e4. https://doi.org/10.1016/j.immuni.2020.03.002

    Article  PubMed  CAS  Google Scholar 

  38. Mestecky J, Russell MW (2009) Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S-IgA at mucosal surfaces. Immunol Lett 124(2):57–62. https://doi.org/10.1016/j.imlet.2009.03.013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Maynard CL, Elson CO, Hatton RD, Weaver CT (2012) Reciprocal interactions of the intestinal microbiota and immune system. Nature 489(7415):231–241. https://doi.org/10.1038/nature11551

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Berni Canani R, Paparo L, Nocerino R, Di Scala C, Della Gatta G, Maddalena Y, Buono A, Voto L, Ercolini D (2019) Gut microbiome as target for innovative strategies against food allergy. Front Immunol. https://doi.org/10.3389/fimmu.2019.00191

    Article  PubMed  PubMed Central  Google Scholar 

  41. Latorre E, Layunta E, Grasa L, Pardo J, García S, Alcalde A, Mesonero JE (2018) Toll-like receptors 2 and 4 modulate intestinal IL-10 differently in ileum and colon. United Eur Gastroenterol J 6(3):446–453. https://doi.org/10.1177/2050640617727180

    Article  CAS  Google Scholar 

  42. Fung TC, Bessman NJ, Hepworth MR, Kumar N, Shibata N, Kobuley D, Wang K, Ziegler CGK, Goc J, Shima T, Umesaki Y, Sartor RB, Sullivan KV, Lawley TD, Kunisawa J, Kiyono H, Sonnenberg GF (2016) Lymphoid-tissue-resident commensal bacteria promote members of the IL-10 cytokine family to establish mutualism. Immunity 44(3):634–646. https://doi.org/10.1016/j.immuni.2016.02.019

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Kotlyarov S, Kotlyarova A (2021) Anti-inflammatory function of fatty acids and involvement of their metabolites in the resolution of inflammation in chronic obstructive pulmonary disease. Int J Mol Sci 22(23):12803. https://doi.org/10.3390/ijms222312803

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Vaughan A, Frazer ZA, Hansbro PM, Yang IA (2019) COPD and the gut-lung axis: the therapeutic potential of fibre. J Thorac Dis 11(Suppl 17):S2173–S2180. https://doi.org/10.21037/jtd.2019.10.40

    Article  PubMed  PubMed Central  Google Scholar 

  45. Opron K, Begley LA, Erb-Downward JR, Freeman C, Madapoosi S, Alexis NE, Barjaktarevic I, Graham Barr R, Bleecker ER, Bowler RP, Christenson SA, Comellas AP, Cooper CB, Couper DJ, Doerschuk CM, Dransfield MT, Han MK, Hansel NN, Hastie AT, Hoffman EA, Kaner RJ, Krishnan J, O’Neal WK, Ortega VE, Paine R 3rd, Peters SP, Michael Wells J, Woodruff PG, Martinez FJ, Curtis JL, Huffnagle GB, Huang YJ (2021) Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort. NPJ Biofilms Microbiomes 7(1):14. https://doi.org/10.1038/s41522-021-00185-9

    Article  PubMed  PubMed Central  Google Scholar 

  46. Garcia-Nuñez M, Millares L, Pomares X, Ferrari R, Pérez-Brocal V, Gallego M, Espasa M, Moya A, Monsó E (2014) Severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease. J Clin Microbiol 52(12):4217–4223. https://doi.org/10.1128/JCM.01967-14

    Article  PubMed  PubMed Central  Google Scholar 

  47. Budden KF, Shukla SD, Rehman SF, Bowerman KL, Keely S, Hugenholtz P, Hansbro PM (2019) Functional effects of the microbiota in chronic respiratory disease. Lancet Respir Med 7(10):907–920. https://doi.org/10.1016/S2213-2600(18)30510-1

    Article  PubMed  Google Scholar 

  48. Toraldo DM, Conte L (2019) Influence of the lung microbiota dysbiosis in chronic obstructive pulmonary disease exacerbations: the controversial use of corticosteroid and antibiotic treatments and the role of eosinophils as a disease marker. J Clin Med Res 11(10):667–675. https://doi.org/10.14740/jocmr3875

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Herath SC, Normansell R, Maisey S, Poole P (2018) Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD009764.pub3

    Article  PubMed  PubMed Central  Google Scholar 

  50. Bourne S, Cohet C, Kim V, Barton A, Tuck A, Aris E, Mesia-Vela S, Devaster JM, Ballou WR, Clarke SC, Wilkinson T (2014) Acute exacerbation and respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study. BMJ Open 4(3):e004546. https://doi.org/10.1136/bmjopen-2013-004546

    Article  PubMed  PubMed Central  Google Scholar 

  51. Lai HC, Lin TL, Chen TW, Kuo YL, Chang CJ, Wu TR, Shu CC, Tsai YH, Swift S, Lu CC (2022) Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory parabacteroides goldsteinii lipopolysaccharide. Gut Microbiota 71:309–321. https://doi.org/10.1136/gutjnl-2020-322599

    Article  CAS  Google Scholar 

Download references

Funding

The authors have not disclosed any funding.

Author information

Authors and Affiliations

  1. Laboratory Human Anatomy, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy

    Francesco De Nuccio

  2. University of Salento, Lecce, Italy

    Prisco Piscitelli

  3. Respiratory Care Unit, “V. Fazzi” Hospital Rehabilitation Department, ASL, 73100, Lecce, Italy

    Domenico Maurizio Toraldo

Authors
  1. Francesco De Nuccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prisco Piscitelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Domenico Maurizio Toraldo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

FD and DMT provided the idea for the article and wrote the manuscript text; all authors reviewed the manuscript.

Corresponding author

Correspondence to Domenico Maurizio Toraldo.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Nuccio, F., Piscitelli, P. & Toraldo, D.M. Gut–lung Microbiota Interactions in Chronic Obstructive Pulmonary Disease (COPD): Potential Mechanisms Driving Progression to COPD and Epidemiological Data. Lung 200, 773–781 (2022). https://doi.org/10.1007/s00408-022-00581-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-022-00581-8

Keywords

Search

Navigation