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Airway microbiome composition correlates with lung function and arterial stiffness in an age-dependent manner


Autoři: Shuen Yee Lee aff001;  Micheál Mac Aogáin aff001;  Kai Deng Fam aff001;  Kar Ling Chia aff001;  Nur A’tikah Binte Mohamed Ali aff001;  Margaret M. C. Yap aff001;  Eric P. H. Yap aff001;  Sanjay H. Chotirmall aff001;  Chin Leong Lim aff001
Působiště autorů: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225636

Souhrn

Objective

To investigate age-associated changes in airway microbiome composition and their relationships with lung function and arterial stiffness among genetically matched young and elderly pairs.

Methods

Twenty-four genetically linked family pairs comprised of younger (≤40 years) and older (≥60 years) healthy participants were recruited (Total n = 48). Lung function and arterial stiffness (carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx)) were assessed. Sputum samples were collected for targeted 16S rRNA gene amplicon sequencing and correlations between microbiome composition, lung function and arterial stiffness were investigated.

Results

Elderly participants exhibited reductions in lung function (FEV1 (p<0.001), FVC (p<0.001) and percentage FEV1/FVC (p = 0.003)) and a 1.3–3.9-fold increase in arterial stiffness (p<0.001) relative to genetically related younger adults. Elderly adults had a higher relative abundance of Firmicutes (p = 0.035) and lower relative abundance of Proteobacteria (p = 0.014), including specific genera Haemophilus (p = 0.024) and Lautropia (p = 0.020) which were enriched in the younger adults. Alpha diversity was comparable between young and elderly pairs (p>0.05) but was inversely associated with lung function (FEV1%Predicted and FVC %Predicted) in the young (p = 0.006 and p = 0.003) though not the elderly (p = 0.481 and p = 0.696). Conversely, alpha diversity was negatively associated with PWV in the elderly (p = 0.01) but not the young (p = 0.569). Specifically, phylum Firmicutes including the genus Gemella were correlated with lung function (FVC %Predicted) in the young group (p = 0.047 and p = 0.040), while Fusobacteria and Leptotrichia were associated with arterial stiffness (PWV) in the elderly (both p = 0.004).

Conclusion

Ageing is associated with increased Firmicutes and decreased Proteobacteria representation in the airway microbiome among a healthy Asian cohort. The diversity and composition of the airway microbiome is independently associated with lung function and arterial stiffness in the young and elderly groups respectively. This suggests differential microbial associations with these phenotypes at specific stages of life with potential prognostic implications.

Klíčová slova:

Aging – Elderly – Geriatrics – Microbiome – Pulmonary function – Saliva – Sputum – Stiffness


Zdroje

1. Budinger GRS, Kohanski RA, Gan W, Kobor MS, Amaral LA, Armanios M, et al. The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop. J Gerontol A Biol Sci Med Sci. 2017;72(11):1492–500. doi: 10.1093/gerona/glx090 28498894

2. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135(10):e146–e603. doi: 10.1161/CIR.0000000000000485 28122885

3. Sharma G, Goodwin J. Effect of aging on respiratory system physiology and immunology. Clin Interv Aging. 2006;1(3):253–60. 18046878

4. Janssens JP, Pache JC, Nicod LP. Physiological changes in respiratory function associated with ageing. Eur Respir J. 1999;13(1):197–205. doi: 10.1034/j.1399-3003.1999.13a36.x 10836348

5. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a "set up" for vascular disease. Circulation. 2003;107(1):139–46. doi: 10.1161/01.cir.0000048892.83521.58 12515756

6. Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study. Hypertension. 2004;43(6):1239–45. doi: 10.1161/01.HYP.0000128420.01881.aa 15123572

7. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values'. Eur Heart J. 2010;31(19):2338–50. doi: 10.1093/eurheartj/ehq165 20530030

8. Jankowich MD, Taveira T, Wu WC. Decreased lung function is associated with increased arterial stiffness as measured by peripheral pulse pressure: data from NHANES III. Am J Hypertens. 2010;23(6):614–9. doi: 10.1038/ajh.2010.37 20224559

9. Zureik M, Benetos A, Neukirch C, Courbon D, Bean K, Thomas F, et al. Reduced pulmonary function is associated with central arterial stiffness in men. Am J Respir Crit Care Med. 2001;164(12):2181–5. doi: 10.1164/ajrccm.164.12.2107137 11751184

10. Barr RG, Ahmed FS, Carr JJ, Hoffman EA, Jiang R, Kawut SM, et al. Subclinical atherosclerosis, airflow obstruction and emphysema: the MESA Lung Study. Eur Respir J. 2012;39(4):846–54. doi: 10.1183/09031936.00165410 22034646

11. Jacobs DR Jr., Yatsuya H, Hearst MO, Thyagarajan B, Kalhan R, Rosenberg S, et al. Rate of decline of forced vital capacity predicts future arterial hypertension: the Coronary Artery Risk Development in Young Adults Study. Hypertension. 2012;59(2):219–25. doi: 10.1161/HYPERTENSIONAHA.111.184101 22203738

12. Bolton CE, Cockcroft JR, Sabit R, Munnery M, McEniery CM, Wilkinson IB, et al. Lung function in mid-life compared with later life is a stronger predictor of arterial stiffness in men: the Caerphilly Prospective Study. Int J Epidemiol. 2009;38(3):867–76. doi: 10.1093/ije/dyn374 19204008

13. Engstrom G, Lind P, Hedblad B, Wollmer P, Stavenow L, Janzon L, et al. Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins. Circulation. 2002;106(20):2555–60. doi: 10.1161/01.cir.0000037220.00065.0d 12427651

14. Zureik M, Kauffmann F, Touboul PJ, Courbon D, Ducimetiere P. Association between peak expiratory flow and the development of carotid atherosclerotic plaques. Arch Intern Med. 2001;161(13):1669–76. doi: 10.1001/archinte.161.13.1669 11434800

15. Polverino F, Celli BR, Owen CA. COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series). Pulm Circ. 2018;8(1):2045894018758528. doi: 10.1177/2045894018758528 29468936

16. Mills NL, Miller JJ, Anand A, Robinson SD, Frazer GA, Anderson D, et al. Increased arterial stiffness in patients with chronic obstructive pulmonary disease: a mechanism for increased cardiovascular risk. Thorax. 2008;63(4):306–11. doi: 10.1136/thx.2007.083493 18024535

17. Qvist L, Nilsson U, Johansson V, Larsson K, Ronmark E, Langrish J, et al. Central arterial stiffness is increased among subjects with severe and very severe COPD: report from a population-based cohort study. Eur Clin Respir J. 2015;2.

18. van Rooyen Y, Schutte AE, Huisman HW, Eloff FC, Du Plessis JL, Kruger A, et al. Inflammation as Possible Mediator for the Relationship Between Lung and Arterial Function. Lung. 2016;194(1):107–15. doi: 10.1007/s00408-015-9804-9 26411588

19. Dickson RP, Huffnagle GB. The Lung Microbiome: New Principles for Respiratory Bacteriology in Health and Disease. PLoS Pathog. 2015;11(7):e1004923. doi: 10.1371/journal.ppat.1004923 26158874

20. Coburn B, Wang PW, Diaz Caballero J, Clark ST, Brahma V, Donaldson S, et al. Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep. 2015;5:10241. doi: 10.1038/srep10241 25974282

21. Dickson RP, Erb-Downward JR, Freeman CM, McCloskey L, Beck JM, Huffnagle GB, et al. Spatial Variation in the Healthy Human Lung Microbiome and the Adapted Island Model of Lung Biogeography. Ann Am Thorac Soc. 2015;12(6):821–30. doi: 10.1513/AnnalsATS.201501-029OC 25803243

22. Bassis CM, Erb-Downward JR, Dickson RP, Freeman CM, Schmidt TM, Young VB, et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio. 2015;6(2):e00037. doi: 10.1128/mBio.00037-15 25736890

23. Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, et al. Analysis of the lung microbiome in the "healthy" smoker and in COPD. PLoS One. 2011;6(2):e16384. doi: 10.1371/journal.pone.0016384 21364979

24. Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. 2010;5(5):e10667. doi: 10.1371/journal.pone.0010667 20498852

25. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178–84. doi: 10.1038/nature11319 22797518

26. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268–73. doi: 10.1126/science.1223490 22674334

27. El Assar M, Angulo J, Vallejo S, Peiro C, Sanchez-Ferrer CF, Rodriguez-Manas L. Mechanisms involved in the aging-induced vascular dysfunction. Front Physiol. 2012;3:132. doi: 10.3389/fphys.2012.00132 22783194

28. Mitchell GF, DeStefano AL, Larson MG, Benjamin EJ, Chen MH, Vasan RS, et al. Heritability and a genome-wide linkage scan for arterial stiffness, wave reflection, and mean arterial pressure: the Framingham Heart Study. Circulation. 2005;112(2):194–9. doi: 10.1161/CIRCULATIONAHA.104.530675 15998672

29. Gursli S, Sandvik L, Bakkeheim E, Skrede B, Stuge B. Evaluation of a novel technique in airway clearance therapy—Specific Cough Technique (SCT) in cystic fibrosis: A pilot study of a series of N-of-1 randomised controlled trials. SAGE Open Med. 2017;5:2050312117697505. doi: 10.1177/2050312117697505 28540046

30. Fan X, Peters BA, Min D, Ahn J, Hayes RB. Comparison of the oral microbiome in mouthwash and whole saliva samples. PLoS One. 2018;13(4):e0194729. doi: 10.1371/journal.pone.0194729 29641531

31. Ma WY, Yang CY, Shih SR, Hsieh HJ, Hung CS, Chiu FC, et al. Measurement of Waist Circumference: midabdominal or iliac crest? Diabetes Care. 2013;36(6):1660–6. doi: 10.2337/dc12-1452 23275359

32. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948. doi: 10.1183/09031936.05.00035205 16264058

33. Nakagomi A, Shoji T, Okada S, Ohno Y, Kobayashi Y. Validity of the augmentation index and pulse pressure amplification as determined by the SphygmoCor XCEL device: a comparison with invasive measurements. Hypertens Res. 2018;41(1):27–32. doi: 10.1038/hr.2017.81 28978987

34. Sutton-Tyrrell K, Najjar SS, Boudreau RM, Venkitachalam L, Kupelian V, Simonsick EM, et al. Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults. Circulation. 2005;111(25):3384–90. doi: 10.1161/CIRCULATIONAHA.104.483628 15967850

35. Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30(3):445–8. doi: 10.1097/HJH.0b013e32834fa8b0 22278144

36. Mac Aogain M, Chandrasekaran R, Lim AYH, Low TB, Tan GL, Hassan T, et al. Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study. Eur Respir J. 2018;52(1).

37. Amplicon PCR, Clean-up, P.C.R. & Index, P.C.R. 16S Metagenomic Sequencing Library Preparation. https://www.illumina.com/content/dam/illumina-support/documents/documentation/chemistry_documentation/16s/16s-metagenomic-library-prep-guide-15044223-b.pdf.

38. Davis NM, Proctor DM, Holmes SP, Relman DA, Callahan BJ. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome. 2018;6(1):226. doi: 10.1186/s40168-018-0605-2 30558668

39. Qaseem A, Wilt TJ, Weinberger SE, Hanania NA, Criner G, van der Molen T, et al. Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease: A Clinical Practice Guideline Update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011;155(3):179–91. doi: 10.7326/0003-4819-155-3-201108020-00008 21810710

40. Seidel J, Valenzano DR. The role of the gut microbiome during host ageing. F1000Res. 2018;7.

41. O’Toole PW, Jeffery IB. Gut microbiota and aging. Science. 2015;350(6265):1214–5. doi: 10.1126/science.aac8469 26785481

42. Murray MA, Chotirmall SH. The Impact of Immunosenescence on Pulmonary Disease. Mediators Inflamm. 2015;2015:692546. doi: 10.1155/2015/692546 26199462

43. Chotirmall SH, Burke CM. Aging and the microbiome: implications for asthma in the elderly? Expert Rev Respir Med. 2015;9(2):125–8. doi: 10.1586/17476348.2015.1002473 25582135

44. Garcia-Nunez M, Millares L, Pomares X, Ferrari R, Perez-Brocal V, Gallego M, et al. Severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease. J Clin Microbiol. 2014;52(12):4217–23. doi: 10.1128/JCM.01967-14 25253795

45. Liu HY, Zhang SY, Yang WY, Su XF, He Y, Zhou HW, et al. Oropharyngeal and Sputum Microbiomes Are Similar Following Exacerbation of Chronic Obstructive Pulmonary Disease. Front Microbiol. 2017;8:1163. doi: 10.3389/fmicb.2017.01163 28690603

46. Wang Z, Bafadhel M, Haldar K, Spivak A, Mayhew D, Miller BE, et al. Lung microbiome dynamics in COPD exacerbations. Eur Respir J. 2016;47(4):1082–92. doi: 10.1183/13993003.01406-2015 26917613

47. Leung JM, Tiew PY, Mac Aogain M, Budden KF, Yong VF, Thomas SS, et al. The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD. Respirology. 2017;22(4):634–50. doi: 10.1111/resp.13032 28342288

48. Sze MA, Dimitriu PA, Suzuki M, McDonough JE, Campbell JD, Brothers JF, et al. Host Response to the Lung Microbiome in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2015;192(4):438–45. doi: 10.1164/rccm.201502-0223OC 25945594

49. Huang YJ, Boushey HA. The Sputum Microbiome in Chronic Obstructive Pulmonary Disease Exacerbations. Ann Am Thorac Soc. 2015;12 Suppl 2:S176–80.

50. O’Dwyer DN, Dickson RP, Moore BB. The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease. J Immunol. 2016;196(12):4839–47. doi: 10.4049/jimmunol.1600279 27260767

51. Budden KF, Shukla SD, Rehman SF, Bowerman KL, Keely S, Hugenholtz P, et al. Functional effects of the microbiota in chronic respiratory disease. Lancet Respir Med. 2019.

52. Carmody LA, Zhao J, Schloss PD, Petrosino JF, Murray S, Young VB, et al. Changes in cystic fibrosis airway microbiota at pulmonary exacerbation. Ann Am Thorac Soc. 2013;10(3):179–87. doi: 10.1513/AnnalsATS.201211-107OC 23802813

53. Takahashi Y, Saito A, Chiba H, Kuronuma K, Ikeda K, Kobayashi T, et al. Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis. Respir Res. 2018;19(1):34. doi: 10.1186/s12931-018-0736-9 29486761

54. Flight WG, Smith A, Paisey C, Marchesi JR, Bull MJ, Norville PJ, et al. Rapid Detection of Emerging Pathogens and Loss of Microbial Diversity Associated with Severe Lung Disease in Cystic Fibrosis. J Clin Microbiol. 2015;53(7):2022–9. doi: 10.1128/JCM.00432-15 25878338

55. Jorth P, Ehsan Z, Rezayat A, Caldwell E, Pope C, Brewington JJ, et al. Direct Lung Sampling Indicates That Established Pathogens Dominate Early Infections in Children with Cystic Fibrosis. Cell Rep. 2019;27(4):1190–204.e3. doi: 10.1016/j.celrep.2019.03.086 31018133

56. Tuleta I, Skowasch D, Aurich F, Eckstein N, Schueler R, Pizarro C, et al. Asthma is associated with atherosclerotic artery changes. PLoS One. 2017;12(10):e0186820. doi: 10.1371/journal.pone.0186820 29073174

57. Steinmann M, Abbas C, Singer F, Casaulta C, Regamey N, Haffner D, et al. Arterial stiffness is increased in asthmatic children. Eur J Pediatr. 2015;174(4):519–23. doi: 10.1007/s00431-014-2423-2 25248341

58. Hosgood HD 3rd, Mongodin EF, Wan Y, Hua X, Rothman N, Hu W, et al. The respiratory tract microbiome and its relationship to lung cancer and environmental exposures found in rural China. Environ Mol Mutagen. 2019.


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