Darcy R Denner1, Naseer Sangwan2, Julia B Becker1, D Kyle Hogarth1, Justin Oldham1, Jamee Castillo1, Anne I Sperling1, Julian Solway1, Edward T Naureckas1, Jack A Gilbert3, Steven R White4. 1. Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, Ill. 2. Biosciences Division (BIO), Argonne National Laboratory, Argonne, Ill. 3. Biosciences Division (BIO), Argonne National Laboratory, Argonne, Ill; Departments of Ecology & Evolution and Surgery, University of Chicago, Chicago, Ill; Institute for Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, Ill; Marine Biological Laboratory, Woods Hole, Mass. 4. Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, Ill. Electronic address: swhite@bsd.uchicago.edu.
Abstract
BACKGROUND: The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. OBJECTIVES: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. METHODS: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. RESULTS: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. CONCLUSION: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use.
BACKGROUND: The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. OBJECTIVES: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. METHODS: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. RESULTS: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. CONCLUSION: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use.
Authors: Markus J Ege; Melanie Mayer; Anne-Cécile Normand; Jon Genuneit; William O C M Cookson; Charlotte Braun-Fahrländer; Dick Heederik; Renaud Piarroux; Erika von Mutius Journal: N Engl J Med Date: 2011-02-24 Impact factor: 91.245
Authors: P G Woodruff; R Khashayar; S C Lazarus; S Janson; P Avila; H A Boushey; M Segal; J V Fahy Journal: J Allergy Clin Immunol Date: 2001-11 Impact factor: 10.793
Authors: Emily S Charlson; Kyle Bittinger; Jun Chen; Joshua M Diamond; Hongzhe Li; Ronald G Collman; Frederic D Bushman Journal: PLoS One Date: 2012-09-06 Impact factor: 3.240
Authors: Leopoldo N Segal; Alexander V Alekseyenko; Jose C Clemente; Rohan Kulkarni; Benjamin Wu; Zhan Gao; Hao Chen; Kenneth I Berger; Roberta M Goldring; William N Rom; Martin J Blaser; Michael D Weiden Journal: Microbiome Date: 2013-07-01 Impact factor: 14.650
Authors: Michael L Walker; Kathryn E Holt; Gary P Anderson; Shu Mei Teo; Peter D Sly; Patrick G Holt; Michael Inouye Journal: Front Immunol Date: 2014-09-23 Impact factor: 7.561
Authors: Kathryn McCauley; Juliana Durack; Ricardo Valladares; Douglas W Fadrosh; Din L Lin; Agustin Calatroni; Petra K LeBeau; Hoang T Tran; Kei E Fujimura; Brandon LaMere; Geil Merana; Kole Lynch; Robyn T Cohen; Jacqueline Pongracic; Gurjit K Khurana Hershey; Carolyn M Kercsmar; Michelle Gill; Andrew H Liu; Haejin Kim; Meyer Kattan; Stephen J Teach; Alkis Togias; Homer A Boushey; James E Gern; Daniel J Jackson; Susan V Lynch Journal: J Allergy Clin Immunol Date: 2019-06-13 Impact factor: 10.793
Authors: Ayse Bilge Ozturk; Benjamin Arthur Turturice; David L Perkins; Patricia W Finn Journal: Curr Allergy Asthma Rep Date: 2017-08-10 Impact factor: 4.806
Authors: Sharon M Carney; Jose C Clemente; Michael J Cox; Robert P Dickson; Yvonne J Huang; Georgios D Kitsios; Kirsten M Kloepfer; Janice M Leung; Tricia D LeVan; Philip L Molyneaux; Bethany B Moore; David N O'Dwyer; Leopoldo N Segal; Stavros Garantziotis Journal: Am J Respir Cell Mol Biol Date: 2020-03 Impact factor: 6.914