Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia

Sisi Du, Xiaojing Wu, Binbin Li, Yimin Wang, Lianhan Shang, Xu Huang, Yudi Xia, Donghao Yu, Naicong Lu, Zhibo Liu, Chunlei Wang, Xinmeng Liu, Zhujia Xiong, Xiaohui Zou, Binghuai Lu, Yingmei Liu, Qingyuan Zhan, Bin Cao

PDF(1504 KB)
PDF(1504 KB)
Front. Med. ›› 2022, Vol. 16 ›› Issue (3) : 389-402. DOI: 10.1007/s11684-021-0856-3
RESEARCH ARTICLE
RESEARCH ARTICLE

Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia

Author information +
History +

Abstract

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R2=0.033; P=0.018), followed by acute kidney injury (AKI; R2=0.032; P=0.011) and plasma MIP-1β level (R2=0.027; P=0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients’ lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.

Keywords

severe community-acquired pneumonia / lung microbiota / clinical improvements / 7-category ordinal scale / Prevotellaceae

Cite this article

Download citation ▾
Sisi Du, Xiaojing Wu, Binbin Li, Yimin Wang, Lianhan Shang, Xu Huang, Yudi Xia, Donghao Yu, Naicong Lu, Zhibo Liu, Chunlei Wang, Xinmeng Liu, Zhujia Xiong, Xiaohui Zou, Binghuai Lu, Yingmei Liu, Qingyuan Zhan, Bin Cao. Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia. Front. Med., 2022, 16(3): 389‒402 https://doi.org/10.1007/s11684-021-0856-3

References

[1]
Liapikou A, Rosales-Mayor E, Torres A. The management of severe community acquired pneumonia in the intensive care unit. Expert Rev Respir Med 2014; 8(3): 293–303
CrossRef Pubmed Google scholar
[2]
Espinoza R, Silva JRLE, Bergmann A, de Oliveira Melo U, Calil FE, Santos RC, Salluh JIF. Factors associated with mortality in severe community-acquired pneumonia: a multicenter cohort study. J Crit Care 2019; 50: 82–86
CrossRef Pubmed Google scholar
[3]
Phua J, Dean NC, Guo Q, Kuan WS, Lim HF, Lim TK. Severe community-acquired pneumonia: timely management measures in the first 24 hours. Crit Care 2016; 20(1): 237
CrossRef Pubmed Google scholar
[4]
Li HY, Guo Q, Song WD, Zhou YP, Li M, Chen XK, Liu H, Peng HL, Yu HQ, Chen X, Liu N, Lü ZD, Liang LH, Zhao QZ, Jiang M. Mortality among severe community-acquired pneumonia patients depends on combinations of 2007 IDSA/ATS minor criteria. Int J Infect Dis 2015; 38: 141–145
CrossRef Pubmed Google scholar
[5]
Torres A, Chalmers JD, Dela Cruz CS, Dominedò C, Kollef M, Martin-Loeches I, Niederman M, Wunderink RG. Challenges in severe community-acquired pneumonia: a point-of-view review. Intensive Care Med 2019; 45(2): 159–171
CrossRef Pubmed Google scholar
[6]
Charlson ES, Bittinger K, Haas AR, Fitzgerald AS, Frank I, Yadav A, Bushman FD, Collman RG. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med 2011; 184(8): 957–963
CrossRef Pubmed Google scholar
[7]
Zakharkina T, Martin-Loeches I, Matamoros S, Povoa P, Torres A, Kastelijn JB, Hofstra JJ, de Wever B, de Jong M, Schultz MJ, Sterk PJ, Artigas A, Bos LDJ. The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia. Thorax 2017; 72(9): 803–810
CrossRef Pubmed Google scholar
[8]
Dickson RP, Erb-Downward JR, Huffnagle GB. Towards an ecology of the lung: new conceptual models of pulmonary microbiology and pneumonia pathogenesis. Lancet Respir Med 2014; 2(3): 238–246
CrossRef Pubmed Google scholar
[9]
Dickson RP, Erb-Downward JR, Martinez FJ, Huffnagle GB. The microbiome and the respiratory tract. Annu Rev Physiol 2016; 78(1): 481–504
CrossRef Pubmed Google scholar
[10]
Dickson RP. The microbiome and critical illness. Lancet Respir Med 2016; 4(1): 59–72
CrossRef Pubmed Google scholar
[11]
Brown RL, Sequeira RP, Clarke TB. The microbiota protects against respiratory infection via GM-CSF signaling. Nat Commun 2017; 8(1): 1512
CrossRef Pubmed Google scholar
[12]
Pettigrew MM, Gent JF, Kong Y, Wade M, Gansebom S, Bramley AM, Jain S, Arnold SLR, McCullers JA. Association of sputum microbiota profiles with severity of community-acquired pneumonia in children. BMC Infect Dis 2016; 16(1): 317
CrossRef Pubmed Google scholar
[13]
Panzer AR, Lynch SV, Langelier C, Christie JD, McCauley K, Nelson M, Cheung CK, Benowitz NL, Cohen MJ, Calfee CS. Lung microbiota is related to smoking status and to development of acute respiratory distress syndrome in critically ill trauma patients. Am J Respir Crit Care Med 2018; 197(5): 621–631
CrossRef Pubmed Google scholar
[14]
Dickson RP, Schultz MJ, van der Poll T, Schouten LR, Falkowski NR, Luth JE, Sjoding MW, Brown CA, Chanderraj R, Huffnagle GB, Bos LDJ; Biomarker Analysis in Septic ICU Patients (BASIC) Consortium. Lung microbiota predict clinical outcomes in critically ill patients. Am J Respir Crit Care Med 2020; 201(5): 555–563
CrossRef Pubmed Google scholar
[15]
Nair GB, Niederman MS. Updates on community acquired pneumonia management in the ICU. Pharmacol Ther 2021; 217: 107663
CrossRef Pubmed Google scholar
[16]
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44(Suppl 2): S27–S72
CrossRef Pubmed Google scholar
[17]
Interventional Pulmonology Group of the Chinese Thoracic Society, Chinese Medical Association. Guideline for diagnostic flexible bronchoscopy in adults (2019). Chin J Tuberc Respir Dis (Zhonghua Jie He He Hu Xi Za Zhi) 2019; 42(8): 573–590 (in Chinese)
Pubmed
[18]
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020; 382(19): 1787–1799
CrossRef Pubmed Google scholar
[19]
Wang Y, Fan G, Horby P, Hayden F, Li Q, Wu Q, Zou X, Li H, Zhan Q, Wang C, Cao B; CAP-China Network. Comparative outcomes of adults hospitalized with seasonal influenza A or B virus infection: application of the 7-category ordinal scale. Open Forum Infect Dis 2019; 6(3): ofz053
CrossRef Pubmed Google scholar
[20]
Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, Fu S, Gao L, Cheng Z, Lu Q, Hu Y, Luo G, Wang K, Lu Y, Li H, Wang S, Ruan S, Yang C, Mei C, Wang Y, Ding D, Wu F, Tang X, Ye X, Ye Y, Liu B, Yang J, Yin W, Wang A, Fan G, Zhou F, Liu Z, Gu X, Xu J, Shang L, Zhang Y, Cao L, Guo T, Wan Y, Qin H, Jiang Y, Jaki T, Hayden FG, Horby PW, Cao B, Wang C. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020; 395(10236): 1569–1578
CrossRef Pubmed Google scholar
[21]
Zhou F, Wang Y, Liu Y, Liu X, Gu L, Zhang X, Pu Z, Yang G, Liu B, Nie Q, Xue B, Feng J, Guo Q, Liu J, Fan H, Chen J, Zhang Y, Xu Z, Pang M, Chen Y, Nie X, Cai Z, Xu J, Peng K, Li X, Xiang P, Zhang Z, Jiang S, Su X, Zhang J, Li Y, Jin X, Jiang R, Dong J, Song Y, Zhou H, Wang C, Cao B; CAP-China Network. Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network. Eur Respir J 2019; 54(2): 1802406
CrossRef Pubmed Google scholar
[22]
Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, Brochard L, Brower R, Esteban A, Gattinoni L, Rhodes A, Slutsky AS, Vincent JL, Rubenfeld GD, Thompson BT, Ranieri VM. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 2012; 38(10): 1573–1582
CrossRef Pubmed Google scholar
[23]
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801–810
CrossRef Pubmed Google scholar
[24]
Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012; 120(4): c179–c184
Pubmed
[25]
Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW Jr, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Prokop CS, Shoham S, Slavin MA, Stevens DA, Thompson GR III, Vazquez JA, Viscoli C, Walsh TJ, Warris A, Wheat LJ, White PL, Zaoutis TE, Pappas PG. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 2020; 71(6): 1367–1376
CrossRef Pubmed Google scholar
[26]
Kelly BJ, Imai I, Bittinger K, Laughlin A, Fuchs BD, Bushman FD, Collman RG. Composition and dynamics of the respiratory tract microbiome in intubated patients. Microbiome 2016; 4(1): 7
CrossRef Pubmed Google scholar
[27]
Venier AG, Leroyer C, Slekovec C, Talon D, Bertrand X, Parer S, Alfandari S, Guerin JM, Megarbane B, Lawrence C, Clair B, Lepape A, Perraud M, Cassier P, Trivier D, Boyer A, Dubois V, Asselineau J, Rogues AM, Thiébaut R; DYNAPYO study group. Risk factors for Pseudomonas aeruginosa acquisition in intensive care units: a prospective multicentre study. J Hosp Infect 2014; 88(2): 103–108
CrossRef Pubmed Google scholar
[28]
Hoang S, Georget A, Asselineau J, Venier AG, Leroyer C, Rogues AM, Thiébaut R. Risk factors for colonization and infection by Pseudomonas aeruginosa in patients hospitalized in intensive care units in France. PLoS One 2018; 13(3): e0193300
CrossRef Pubmed Google scholar
[29]
Bachta KER, Allen JP, Cheung BH, Chiu CH, Hauser AR. Systemic infection facilitates transmission of Pseudomonas aeruginosa in mice. Nat Commun 2020; 11(1): 543
CrossRef Pubmed Google scholar
[30]
Hilton SK, Castro-Nallar E, Pérez-Losada M, Toma I, McCaffrey TA, Hoffman EP, Siegel MO, Simon GL, Johnson WE, Crandall KA. Metataxonomic and metagenomic approaches vs. culture-based techniques for clinical pathology. Front Microbiol 2016; 7: 484
CrossRef Pubmed Google scholar
[31]
Emonet S, Lazarevic V, Leemann Refondini C, Gaïa N, Leo S, Girard M, Nocquet Boyer V, Wozniak H, Després L, Renzi G, Mostaguir K, Dupuis Lozeron E, Schrenzel J, Pugin J. Identification of respiratory microbiota markers in ventilator-associated pneumonia. Intensive Care Med 2019; 45(8): 1082–1092
CrossRef Pubmed Google scholar
[32]
Chawla LS, Amdur RL, Faselis C, Li P, Kimmel PL, Palant CE. Impact of acute kidney injury in patients hospitalized with pneumonia. Crit Care Med 2017; 45(4): 600–606
CrossRef Pubmed Google scholar
[33]
Husain-Syed F, Slutsky AS, Ronco C. Lung-kidney cross-talk in the critically ill patient. Am J Respir Crit Care Med 2016; 194(4): 402–414
CrossRef Pubmed Google scholar
[34]
Polverino F, Laucho-Contreras ME, Petersen H, Bijol V, Sholl LM, Choi ME, Divo M, Pinto-Plata V, Chetta A, Tesfaigzi Y, Celli BR, Owen CA. A pilot study linking endothelial injury in lungs and kidneys in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2017; 195(11): 1464–1476
CrossRef Pubmed Google scholar
[35]
Hepokoski M, Englert JA, Baron RM, Crotty-Alexander LE, Fuster MM, Beitler JR, Malhotra A, Singh P. Ventilator-induced lung injury increases expression of endothelial inflammatory mediators in the kidney. Am J Physiol Renal Physiol 2017; 312(4): F654–F660
CrossRef Pubmed Google scholar
[36]
Rogers PD, Thornton J, Barker KS, McDaniel DO, Sacks GS, Swiatlo E, McDaniel LS. Pneumolysin-dependent and-independent gene expression identified by cDNA microarray analysis of THP-1 human mononuclear cells stimulated by Streptococcus pneumoniae. Infect Immun 2003; 71(4): 2087–2094
CrossRef Pubmed Google scholar
[37]
Turturice BA, McGee HS, Oliver B, Baraket M, Nguyen BT, Ascoli C, Ranjan R, Rani A, Perkins DL, Finn PW. Atopic asthmatic immune phenotypes associated with airway microbiota and airway obstruction. PLoS One 2017; 12(10): e0184566
CrossRef Pubmed Google scholar
[38]
Zemanick ET, Wagner BD, Robertson CE, Ahrens RC, Chmiel JF, Clancy JP, Gibson RL, Harris WT, Kurland G, Laguna TA, McColley SA, McCoy K, Retsch-Bogart G, Sobush KT, Zeitlin PL, Stevens MJ, Accurso FJ, Sagel SD, Harris JK. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J 2017; 50(5): 1700832
CrossRef Pubmed Google scholar
[39]
Tsang TK, Lee KH, Foxman B, Balmaseda A, Gresh L, Sanchez N, Ojeda S, Lopez R, Yang Y, Kuan G, Gordon A. Association between the respiratory microbiome and susceptibility to influenza virus infection. Clin Infect Dis 2020; 71(5): 1195–1203
CrossRef Pubmed Google scholar
[40]
Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, Li Y, Shen N, Ghedin E, Morris A, Diaz P, Huang L, Wikoff WR, Ubeda C, Artacho A, Rom WN, Sterman DH, Collman RG, Blaser MJ, Weiden MD. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol 2016; 1(5): 16031
CrossRef Pubmed Google scholar
[41]
Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K, Curtis JL, Flores SC, Fontenot AP, Ghedin E, Huang L, Jablonski K, Kleerup E, Lynch SV, Sodergren E, Twigg H, Young VB, Bassis CM, Venkataraman A, Schmidt TM, Weinstock GM; Lung HIV Microbiome Project. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med 2013; 187(10): 1067–1075
CrossRef Pubmed Google scholar
[42]
Li X, Sun Y, An Y, Wang R, Lin H, Liu M, Li S, Ma M, Xiao C. Air pollution during the winter period and respiratory tract microbial imbalance in a healthy young population in Northeastern China. Environ Pollut 2019; 246: 972–979
CrossRef Pubmed Google scholar
[43]
Larsen JM, Steen-Jensen DB, Laursen JM, Søndergaard JN, Musavian HS, Butt TM, Brix S. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota. PLoS One 2012; 7(2): e31976
CrossRef Pubmed Google scholar
[44]
Thorsen J, Rasmussen MA, Waage J, Mortensen M, Brejnrod A, Bønnelykke K, Chawes BL, Brix S, Sørensen SJ, Stokholm J, Bisgaard H. Infant airway microbiota and topical immune perturbations in the origins of childhood asthma. Nat Commun 2019; 10(1): 5001
CrossRef Pubmed Google scholar

Acknowledgements

This study was funded by the National Key Research and Development Program of China (No. 2017YFC1309301), the CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2018-I2M-1-003), the National Science Grant for Distinguished Young Scholars (No. 81425001/H0104), and the Ministry of Science and Technology of China (No. 2017ZX10103004).

Compliance with ethics guidelines

Sisi Du, Xiaojing Wu, Binbin Li, Yimin Wang, Lianhan Shang, Xu Huang, Yudi Xia, Donghao Yu, Naicong Lu, Zhibo Liu, Chunlei Wang, Xinmeng Liu, Zhujia Xiong, Xiaohui Zou, Binghuai Lu, Yingmei Liu, Qingyuan Zhan, and Bin Cao declare that they have no competing interests. Our study was conducted in China-Japan Friendship Hospital, Beijing, China, and approved by the China-Japan Friendship Hospital Ethics Committee (Approval No. 2018-20-K15). It was conducted in accordance with the he Helsinki Declaration of 1975, as revised in 2000 (5). We obtained written informed consent from all enrolled patients or their legal representative for patients who were unable to provide consent.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-021-0856-3 and is accessible for authorized users.

RIGHTS & PERMISSIONS

2021 Higher Education Press
AI Summary AI Mindmap
PDF(1504 KB)

Accesses

Citations

Detail

Sections
Recommended

/