Abstract
Bacterial infection of lung airways underlies some of the main complications of COPD, significantly impacting disease progression and outcome. Colonization by bacteria may further synergize, amplify, or trigger pathways of tissue damage started by cigarette smoke, contributing to the characteristic airway inflammation and alveolar destruction of COPD. We sought to elucidate the presence and types of lung bacterial populations in different stages of COPD, aimed at revealing important insights into the pathobiology of the disease. Sequencing of the bacterial small subunit ribosomal RNA gene in 55 well-characterized clinical lung samples, revealed the presence of Novosphingobium spp. (>2% abundance) in lungs of patients with GOLD 3-GOLD 4 COPD, cystic fibrosis and a subset of control individuals. Novosphingobium-specific quantitative PCR was concordant with the sequence data and high levels of Novosphingobium spp. were quantifiable in advanced COPD, but not from other disease stages. Using a mouse model of subacute lung injury due to inhalation of cigarette smoke, bronchoalveolar lavage neutrophil and macrophage counts were significantly higher in mice challenged intratracheally with N. panipatense compared to control mice (p<0.01). Frequencies of neutrophils and macrophages in lung tissue were increased in mice challenged with N. panipatense at room air compared to controls. However, we did not observe an interaction between N. panipatense and subacute cigarette smoke exposure in the mouse. In conclusion, Novosphingobium spp. are present in more severe COPD disease, and increase inflammation in a mouse model of smoke exposure.
Highlights
Diverse microbial communities are found in each of the different environments of human body, where they interact with resident inflammatory cells in both health and disease [1,2,3,4,5,6]
Quantification of Novosphingobium in human lung tissues of chronic obstructive pulmonary disease (COPD) patients and controls Of the above list of bacteria identified in lungs, we focused in particular in Novosphingobium spp
Based on deep DNA sequencing, we estimated the number of bacterial species in lung tissues obtained from normal lungs and from diseased lungs by extrapolation based on amplified and sequenced 16S rRNA genes
Summary
Diverse microbial communities are found in each of the different environments of human body, where they interact with resident inflammatory cells in both health and disease [1,2,3,4,5,6]. The respiratory tract, like the gastrointestinal and skin systems, is continuously exposed to environmental agents; many pulmonary diseases lead to increased risk of infections and altered microbial communities [2,3,9,10]. It is anticipated that the better understanding of the microbiome in healthy and diseased lungs may better inform how diseases are modified in their course by infection and provide novel means to implement disease-specific treatments [11]. The lung is continuously challenged by inhaled particulates and microorganisms, and yet, healthy individuals rarely have bacteria isolated from their airways. There is a growing body of evidence of organisms, not identifiable by classical cultivation efforts, present within the human airway [14,15,16,17]
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