Hospital Universitari del Parc Taulí, Sabadell, Spain
The respiratory microbiome: a new frontier in medicine
Hospital Universitary del Parc Taulí, Sabadell, Spain.
Bronchial colonization by potentially pathogenic bacteria is common in stable chronic obstructive pulmonary disease (COPD), and in about a half of patients positive cultures for Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis are found during stability periods. Available culture techniques are not suitable for the identification of an important part of the bacterial flora inhabitant of the respiratory mucosa, however. Most bacteria present do not grow adequately on commonly used selective cultures, and are masked by the presence of other bacteria with faster growing. Through independent culture techniques, such as amplification and sequencing, it is possible to determine the composition of bronchial microbiome, both bronchial and viral, defining the relationships between the colonizing flora and MPOC. The use of these techniques in bronchial secretions has shown the existence in a diverse microbiome in COPD, and a predominant presence of bacteria from the phylum Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes.
The bacterial flora observed in patients with COPD alters the pattern of continuity observed in the oropharynx and the bronchial tree of normal subjects, through a partial disappearance of microorganisms common in the healthy population. The magnitude of these changes parallels the severity of the disease, with a relative increase in the proportion of Proteobacteria in severe patients, inversely correlated with the decrease of Firmicutes in advanced COPD. Thus, the bacterial diversity in the respiratory tract appears to be clearly higher in the healthy subject and the patient with mild-moderate COPD, to be replaced in severe COPD by a narrow range of microorganisms, with a high proportion of potentially pathogenic bacteria mainly from the genera Streptococcus, Haemophilus and Moraxella. In patients with severe COPD, frequent colonization by Pseudomonas aeruginosa does not determine a change in the bronchial flora as a whole, which has a similar spectrum in all patients with advanced disease, independently of their colonizing patterns.
The study of the bacterial flora in COPD exacerbations have shown increases in specific bacterial genera in most patients, which include in most cases one or more potentially pathogenic species. These increases in many cases are not identified by culture, a finding that have confirmed the insufficient sensitivity of conventional techniques for identifying causative pathogens in COPD. This approach have shown that the bacterial pattern in exacerbations from patients colonized by Pseudomonas aeruginosa, when identified from independent culture techniques, are similar to patterns found in non-colonized patients, supporting the hypothesis that microorganisms causing exacerbations in Pseudomonas-colonized COPD patients are not different from the pathogens related to bronchial infections in non-colonized patients, and the colonizing role of Pseudomonas aeruginosa continues, both in stability periods and in exacerbations. These findings from microbiome analysis have potential implications for recommendations in therapeutic guidelines.
One additional advantage of the identification of the composition of respiratory microbiome by culture-independent techniques in respiratory samples is the characterization of the functional features of the bacterial genome, through metagenomics. This approach has shown that in COPD exacerbations the functional activity of the background flora may change, in spite of the absence of changes in their composition, with increases in the abundance of genes involved in carbohydrate metabolism and carcinogenesis, and parallel decreases in genes related to cell growth and catabolism.
Thus, the introduction of microbiological identification techniques not based on culture has demonstrated that the diversity of bacterial flora is reduced with advanced COPD, with an overrepresentation of potentially pathogenic microorganisms. In exacerbations, 16S rRNA gene sequencing have identified causal pathogenic bacteria which not recovered through cultures, and functional changes in bacterial flora with potential clinical significance.
Eduard Monsó graduated in Medicine from Universitat de Barcelona in 1981, and attained his Ph.D. Degree in Medicine at the Universitat Autònoma de Barcelona in 1987. He finished his training in Respiratory Medicine in 1985, working after his degree at the Institut Català de la Salud, and is currently Head of the Department of Respiratory Diseases at the Hospital Universitari del Parc Taulí de Sabadell and professor at the Universitat Autónoma de Barcelona. His research interests focused on COPD, bronchial infections, lung cancer, endoscopy techniques, respiratory epidemiology, occupational lung diseases and telemedicine. He is currently Head of the Research Group in Respiratory Diseases Metropolitana Nord de Barcelona (RESPINORD-BCN), part of Centro de Investigación Biomédica en Red de Enfermedades Respiratorias – Ciberes – Instituto de Salud Carlos III. Dr. Eduard Monsó is author of 150 published research papers.