Publicação
Oral microbial and inflammatory signatures of chronic obstructive pulmonary disease
| Resumo: | Chronic obstructive pulmonary disease (COPD) affects approximately 10% of the world's population and is currently considered the third leading cause of death worldwide. COPD is a chronic inflammatory condition of the lungs, highly heterogeneous and difficult to treat and manage, being punctuated by exacerbations, which are events of increased symptoms. In recent years, numerous studies have been conducted to understand and clarify the pathophysiological mechanisms of this disease, discover biomarkers, and propose effective strategies for disease management, such as pulmonary rehabilitation. Pulmonary rehabilitation is the most cost-effective, non-pharmacological intervention for COPD management. It is thought that the composition and abundance of lung microbiota are determined by the balance between microbial migration from the oral cavity/upper airways (microaspiration) and host elimination mechanisms (mucociliary clearance and alveolar macrophage patrol). Chronic lung inflammation impairs the elimination mechanisms, giving bacteria an exceptional opportunity to proliferate in the airways, forming a resident community. Airway microbiota has been implicated in the course and progression of COPD. Although oral microbiota has been pointed as the primary bacterial reservoir of the lower airways, the association between oral microbiota composition and COPD has been neglected. Therefore, the main objective of this thesis was to fill this gap in knowledge and uncover the oral microbial and inflammatory signatures of COPD and understand the interplay between oral microbiota and the immune system of people with COPD in stability, under the influence of pulmonary rehabilitation and during exacerbations. To achieve this, we conducted three pioneer studies, where we found that oral microbiota is significantly different between people with COPD and healthy individuals, showing promise for disease stratification and exhibiting signatures of disease severity and exacerbations, in stability. Additionally, we showed that the interaction between oral microbiota and the immune system contributes, at least in part, to the responsiveness to pulmonary rehabilitation in domains such as exercise capacity, dyspnoea during exercise, and symptoms reduction. Finally, we observed that oral microbiota displays consistent patterns of change associated with the onset of exacerbations and signatures of inflammatory responses that are activated during these periods of increased symptoms. These new findings validate the use of saliva for COPD assessment and highlight the significant role played by oral microbiota, especially by genus Prevotella, in the context of this disease, emphasizing the potential of non-invasive sampling and making a significant contribution to the field of chronic respiratory diseases. Taken together, our results provide a foundation for future research on new microbiota-based therapies and personalized medicine, with the promise of revolutionizing COPD management strategies. The limitations of the studies and the need for validation and further investigation underscore the heterogeneity and complexity of COPD and the importance of exploring multiple facets of the disease to develop effective interventions and treatments. |
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| Autores principais: | Dias, Sara Melo |
| Assunto: | COPD Saliva Oral microbiota Inflammation Pulmonary rehabilitation Responsiveness Exacerbations |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | Chronic obstructive pulmonary disease (COPD) affects approximately 10% of the world's population and is currently considered the third leading cause of death worldwide. COPD is a chronic inflammatory condition of the lungs, highly heterogeneous and difficult to treat and manage, being punctuated by exacerbations, which are events of increased symptoms. In recent years, numerous studies have been conducted to understand and clarify the pathophysiological mechanisms of this disease, discover biomarkers, and propose effective strategies for disease management, such as pulmonary rehabilitation. Pulmonary rehabilitation is the most cost-effective, non-pharmacological intervention for COPD management. It is thought that the composition and abundance of lung microbiota are determined by the balance between microbial migration from the oral cavity/upper airways (microaspiration) and host elimination mechanisms (mucociliary clearance and alveolar macrophage patrol). Chronic lung inflammation impairs the elimination mechanisms, giving bacteria an exceptional opportunity to proliferate in the airways, forming a resident community. Airway microbiota has been implicated in the course and progression of COPD. Although oral microbiota has been pointed as the primary bacterial reservoir of the lower airways, the association between oral microbiota composition and COPD has been neglected. Therefore, the main objective of this thesis was to fill this gap in knowledge and uncover the oral microbial and inflammatory signatures of COPD and understand the interplay between oral microbiota and the immune system of people with COPD in stability, under the influence of pulmonary rehabilitation and during exacerbations. To achieve this, we conducted three pioneer studies, where we found that oral microbiota is significantly different between people with COPD and healthy individuals, showing promise for disease stratification and exhibiting signatures of disease severity and exacerbations, in stability. Additionally, we showed that the interaction between oral microbiota and the immune system contributes, at least in part, to the responsiveness to pulmonary rehabilitation in domains such as exercise capacity, dyspnoea during exercise, and symptoms reduction. Finally, we observed that oral microbiota displays consistent patterns of change associated with the onset of exacerbations and signatures of inflammatory responses that are activated during these periods of increased symptoms. These new findings validate the use of saliva for COPD assessment and highlight the significant role played by oral microbiota, especially by genus Prevotella, in the context of this disease, emphasizing the potential of non-invasive sampling and making a significant contribution to the field of chronic respiratory diseases. Taken together, our results provide a foundation for future research on new microbiota-based therapies and personalized medicine, with the promise of revolutionizing COPD management strategies. The limitations of the studies and the need for validation and further investigation underscore the heterogeneity and complexity of COPD and the importance of exploring multiple facets of the disease to develop effective interventions and treatments. |
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