Publicação
Immune cell and microenvironment crosstalk in fibrotic interstitial lung diseases
| Resumo: | Interstitial lung diseases (ILDs) constitute a heterogeneous group of lung parenchymal pathologies with high diagnostic complexity and associated with significant morbidity and mortality. Some of these pathologies may present a fibrotic phenotype and continue to progress regardless of therapy. Hypersensitivity pneumonitis (HP), an ILD associated with repeated and prolonged inhalation of antigens, particularly relevant in the northern region of Portugal, is the most prevalent ILD in the FIBRALUNG cohort, justifying its inclusion in this study. Another major focus of this project was the lung microbiome, as it has been described as being associated with the different phenotypes of these diseases. The main objective of this study was to characterize the lung microbiome associated with fibrotic HP, comparing it not only with non-fibrotic forms of the disease, but also with participants without ILD or with non-fibrotic tobaccoassociated ILD, and with other types of ILD, such as idiopathic pulmonary fibrosis (IPF), considering the prototype of progressive fibrotic disease. Microbial DNA sequencing of bronchoalveolar lavage (BAL) samples analyzed the diversity and composition of the lung microbiome and associated them with sociodemographic and clinical variables. The results revealed significant differences in microbial composition between groups, particularly in fibrotic HP, with a greater abundance of genera associated with the oral microbiota, such as Fusobacterium, Porphyromonas and Selenomonas, suggesting a link with the oral-pulmonary axis. Further analysis of the salivary microbiome of these patients could contribute to a better understanding of the impact of the microbiome on the susceptibility and progression of these diseases. There was also a significant association between the microbial profile of fibrotic HP and the diffusing capacity of carbon monoxide (DLCO). This data suggests that the microbiome may play not only a descriptive but also a potentially functional role in the progression of fibrotic HP, and that clinical variables like DLCO may help identify subgroups of patients with distinct microbial signatures. A comprehensive study that allows correlating microbial composition with a possible progression profile could contribute to the early identification and reporting of these patients. This study contributed to a better understanding of HP and the role of the microbiome in its progression, pointing to potential microbial biomarkers associated with fibrosis. Further work on this topic could support clinical practice by enabling more accurate patient stratification, improving differential diagnosis, and paving the way for personalized microbiome-based therapeutic strategies. |
|---|---|
| Autores principais: | Meneses, Alexandra Sofia Gomes |
| Assunto: | Interstitial lung diseases Hypersensitivity pneumonitis Lung microbiome Pulmonary fibrosis Progressive fibrotic diseases |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | Interstitial lung diseases (ILDs) constitute a heterogeneous group of lung parenchymal pathologies with high diagnostic complexity and associated with significant morbidity and mortality. Some of these pathologies may present a fibrotic phenotype and continue to progress regardless of therapy. Hypersensitivity pneumonitis (HP), an ILD associated with repeated and prolonged inhalation of antigens, particularly relevant in the northern region of Portugal, is the most prevalent ILD in the FIBRALUNG cohort, justifying its inclusion in this study. Another major focus of this project was the lung microbiome, as it has been described as being associated with the different phenotypes of these diseases. The main objective of this study was to characterize the lung microbiome associated with fibrotic HP, comparing it not only with non-fibrotic forms of the disease, but also with participants without ILD or with non-fibrotic tobaccoassociated ILD, and with other types of ILD, such as idiopathic pulmonary fibrosis (IPF), considering the prototype of progressive fibrotic disease. Microbial DNA sequencing of bronchoalveolar lavage (BAL) samples analyzed the diversity and composition of the lung microbiome and associated them with sociodemographic and clinical variables. The results revealed significant differences in microbial composition between groups, particularly in fibrotic HP, with a greater abundance of genera associated with the oral microbiota, such as Fusobacterium, Porphyromonas and Selenomonas, suggesting a link with the oral-pulmonary axis. Further analysis of the salivary microbiome of these patients could contribute to a better understanding of the impact of the microbiome on the susceptibility and progression of these diseases. There was also a significant association between the microbial profile of fibrotic HP and the diffusing capacity of carbon monoxide (DLCO). This data suggests that the microbiome may play not only a descriptive but also a potentially functional role in the progression of fibrotic HP, and that clinical variables like DLCO may help identify subgroups of patients with distinct microbial signatures. A comprehensive study that allows correlating microbial composition with a possible progression profile could contribute to the early identification and reporting of these patients. This study contributed to a better understanding of HP and the role of the microbiome in its progression, pointing to potential microbial biomarkers associated with fibrosis. Further work on this topic could support clinical practice by enabling more accurate patient stratification, improving differential diagnosis, and paving the way for personalized microbiome-based therapeutic strategies. |
|---|