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Original research
Gut microbiota composition and metabolite profiling in smokers: a comparative study between emphysema and asymptomatic individuals with therapeutic implications
  1. Se Hee Lee1,2,
  2. Jiseon Kim1,
  3. Na Hyun Kim1,
  4. Ock-Hwa Kim1,3,
  5. Chang-Ho Shon1,
  6. Su Jung Kim4,
  7. Youngwon Jang1,
  8. Sunmi Yun5,
  9. Se Eun Lim5,
  10. So Yi Jung5,
  11. Hyun Ju Yoo4,
  12. Sun-Hee Heo1,
  13. Sei Won Lee1
  1. 1 Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  2. 2 Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
  3. 3 Division of Pulmonology, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Sejong Hospital, Chungnam National University, Sejong, Republic of Korea
  4. 4 Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  5. 5 Metagenome Service Department, Macrogen Inc, Seoul, Republic of Korea
  1. Correspondence to Dr Sei Won Lee, Pulmonology and Critical care, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; seiwon{at}


Background Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema.

Methods We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation.

Results Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3+CD4+IL-17+ T-cell population in the lung and spleen.

Conclusion Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema.

  • emphysema
  • COPD pathology

Data availability statement

The data that support the findings of this study are available from the corresponding author (SWL), upon reasonable request.

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Data availability statement

The data that support the findings of this study are available from the corresponding author (SWL), upon reasonable request.

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  • SHL and JK are joint first authors.

  • SHL and JK contributed equally.

  • Contributors SWL developed the concept and designed the experiment. SWL and YJ enrolled participants and collected clinical samples. JK, SHL and SWL developed the image reconstruction and analysis methods used in the study. JK, NHK, O-HK, C-HS and S-HH performed animal experiments. SJK and HJY performed metabolome analysis. SY, SEL and SYJ performed microbiome analysis. SHL, JK and SWL wrote the first draft of the manuscript and all authors contributed to redrafting the manuscript. The guarantor is SWL.

  • Funding This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1A2C1008431, 2023R1A2C2006688, RS-2023-00222687, SWL), Basic Science Research Program through the NRF of Korea funded by the Ministry of Education (No. 2020R1I1A1A01069464, JK) and the Bio & Medical Technology Development Program of NRF funded by the Korean government (MSIT) (No. 2022M3A9G8017220).

  • Competing interests None declared.

  • 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.