Comparison of the Respiratory Microbiome in Healthy Nonsmokers and Smokers

Abstract

Rationale: Results from 16S rDNA-encoding gene sequence-based, culture-independent techniques have led to conflicting conclusions about the composition of the lower respiratory tract microbiome. Objectives: To compare the microbiome of the upper and lower respiratory tract in healthy HIV-uninfected nonsmokers and smokers in a multicenter cohort. Methods: Participants were nonsmokers and smokers without significant comorbidities. Oral washes and bronchoscopic alveolar lavages were collected in a standardized manner. Sequence analysis of bacterial 16S rRNA-encoding genes was performed, and the neutral model in community ecology was used to identify bacteria that were the most plausible members of a lung microbiome. Measurements and Main Results: Sixty-four participants were enrolled. Most bacteria identified in the lung were also in the mouth, but specific bacteria such as Enterobacteriaceae, Haemophilus, Methylobacterium, and Ralstonia species were disproportionally represented in the lungs compared with values predicted by the neutral model. Tropheryma was also in the lung, but not the mouth. Mouth communities differed between nonsmokers and smokers in species such as Porphyromonas, Neisseria, and Gemella, but lung bacterial populations did not. Conclusions: This study is the largest to examine composition of the lower respiratory tract microbiome in healthy individuals and the first to use the neutral model to compare the lung to the mouth. Specific bacteria appear in significantly higher abundance in the lungs than would be expected if they originated from the mouth, demonstrating that the lung microbiome does not derive entirely from the mouth. The mouth microbiome differs in nonsmokers and smokers, but lung communities were not significantly altered by smoking.

Cigarette smoking and the oral microbiome in a large study of American adults

“…Loss of beneficial oral species due to smoking can lead to pathogen colonization and ultimately to disease; this contention is strongly supported by the well-established role of smoking in the onset and progression of periodontitis (Nociti et al, 2015). Previous studies have shown alterations in the abundance of selected oral bacteria in smokers compared with non-smokers (Colman et al, 1976;Ertel et al, 1991;Charlson et al, 2010;Kumar et al, 2011;Hugoson et al, 2012;Morris et al, 2013;Belstrom et al, 2014;Mason et al, 2015); however, results across these studies are largely inconsistent, possibly due to small sample sizes in some, use of different sampling sites in the mouth and use of different laboratory methodologies, some of which impose limitations on bacterial profiling.…”

A Brave New World: The Lung Microbiota in an Era of Change

“…One challenging observation is that the lower airway microbiome is more similar to the upper airway microbiome of the same individual than it is to the lung microbiome of a different person (17). Although part of this might be explained if significant carryover had occurred, most data suggest substantial diversity in healthy individuals (7)(8)(9)19). Therefore, it is important to establish the degree of overlap between different individuals.…”

“…Among various factors, the low culturable bacterial burden in the lung, contamination with upper airway microbiota during sampling, and the difficulties in growing fastidious bacteria have contributed to the presumption that the lung is sterile (3,4). With the use of culture-independent techniques, there is now substantial literature identifying the presence of bacteria products in the lower airways of normal individuals (5)(6)(7)(8). Data from quantitative PCR for 16S ribosomal RNA (rRNA) genes confirm that the bacterial burden in the lower airways is less than in the upper airways.…”

“…It is therefore expected that an unfavorable signal-to-noise ratio will commonly occur when trying to evaluate the lung microbiome of airways with low bacterial burden. New computational background subtraction techniques based on mathematical modeling, such as a neutral model, single-sided outlier test and SourceTracker, may account for carryover and have the potential to identify true lung taxa (7,17,18).…”

Le microbiome pulmonaire en 2015

“…Jusqu'à récemment, les données publiées concernaient essentiellement les microbiomes digestif, cutané, buccal ou génital et leurs liens avec différentes pathologies comme par exemple le diabète. Mais, très récemment, de nombreux microorganismes (bactéries, virus, champignons) ont également été mis en évidence dans les voies aériennes inférieures des sujets en bonne santé, rendant caduque le concept classique de stérilité des voies aériennes normales [1][2][3][4][5]. Plusieurs questions se posent aujourd'hui : ces germes sont-ils des « touristes » ou des résidents permanents du tractus respiratoire ?…”