The Challenging Road of Moving from Association to Causation for Microbiome Research in Idiopathic Pulmonary Fibrosis.
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ABSTRACT:
SUBMITTER: Segal LN
PROVIDER: S-EPMC6515869 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease of unknown cause. Current evidence suggests that it arises in genetically susceptible individuals as a consequence of an aberrant wound-healing response following repetitive alveolar injury. Overt respiratory infection and immunosuppression carry a high mortality, while polymorphisms in genes related to epithelial integrity and host defence predispose to IPF. Recent advances in sequencing technologies have allowed the use of molecular microbial technologies to characterise the respiratory microbiota in patients with IPF. Studies have suggested that changes in the overall bacterial burden are related to disease progression and highlighted significant differences between the microbiota in IPF subjects and healthy controls. Indeed differences in the microbiota between IPF patients may differentiate those with stable compared to progressive disease. As our understanding of the IPF microbiome evolves, along with refinement and advances in sampling and sequencing methodologies we may be able to use microbial signatures as a biomarker to guide prognostication and even treatment stratification in this devastating disease.
| S-EPMC5497092 | biostudies-literature
Project description:A little more than 10 years ago, the completed sequencing of the human genome boldly promised to usher in an era of enhanced understanding and accelerated development of treatments for most human diseases. Ten years later, many of these therapeutic goals have not been reached, but genomic technologies have dramatically enhanced our understanding of how genes and gene networks contribute to the pathogenesis of disease. In this review, we describe how genomic technologies have shaped our study of idiopathic pulmonary fibrosis (IPF), a devastating, progressive scarring of the lung parenchyma, a disease without a known cause, or treatment. We frame the important genomic discoveries in IPF of the previous decade in the clinical context of establishing a diagnosis of IPF and predicting the prognosis. Gene expression profiling of peripheral blood will help identify potential biomarkers for assessing the clinical severity of IPF. We highlight the growth of epigenetic research in IPF, including the contribution of microRNAs to the pathogenesis of disease. We suggest that the full power of genomic discoveries in IPF will be realized when researchers apply these techniques prospectively in large collaborative studies across institutions, support the training of young investigators in genomics, and employ systems biology approaches to the interpretation of genomic data.
| S-EPMC3229869 | biostudies-literature
Project description:Patient-reported outcomes (PROs) include questionnaires or surveys that ask patients for their perceptions about things like symptoms they are experiencing or quality of life. For incurable, morbid, life-shortening conditions like idiopathic pulmonary fibrosis (IPF), PROs are particularly germane: They elucidate for clinicians and researchers what it is like for patients to live with such a disease, and they may detect important treatment effects not captured by other metrics (eg, pulmonary physiology). However, a relative paucity of research on PROs in IPF has left significant knowledge gaps in this area and contributed to the timidity investigators have about using PROs as prominent outcomes in IPF drug trials. Additional research on existing instruments is needed to establish or bolster their basic psychometric properties in IPF. When PROs are used as end points in therapeutic trials, analyzing PRO response data can be challenging, but these challenges can be overcome with a transparent, thoughtful, and sophisticated statistical approach. In this article, we discuss some of the basics of PRO assessment, existing knowledge gaps in IPF-related PRO research, and the potential usefulness of using PROs in IPF trials and conclude by offering specific recommendations for an approach to analyzing repeated-measures PRO data from IPF trials.
| S-EPMC3425334 | biostudies-other
Project description: Not available
| S-BSST12 | biostudies-other
Project description:The interest in the lung microbiome and virome and their contribution to the pathogenesis, perpetuation and progression of idiopathic pulmonary fibrosis (IPF) has been increasing during the last decade. The utilization of high-throughput sequencing to detect microbial and/or viral genetic material in bronchoalveolar lavage fluid or lung tissue samples has amplified the ability to identify and quantify specific microbial and viral populations. In stable IPF, higher microbial burden is associated with worse prognosis but no specific microbe has been identified to contribute to this. Additionally, no causative relation has been established. Regarding viral infections, although in the past they have been associated with IPF, causation has not been proved. Although in the past the diagnosis of acute exacerbation of IPF (AE-IPF) was not considered in patients with overt infection, this was amended in the last few years and infection is considered a cause for exacerbation. Besides this, a higher microbial burden has been found in the lungs of patients with AE-IPF and an association with higher morbidity and mortality has been confirmed. In contrast, an association of AE-IPF with viral infection has not been established. Despite the progress during the last decade, a comprehensive knowledge of the microbiome and virome in IPF and their role in disease pathogenesis are yet elusive. Although association with disease severity, risk for progression and mortality has been established, causation has not been proven and the potential use as a biomarker or the benefits of antimicrobial therapeutic strategies are yet to be determined.
| S-EPMC8074588 | biostudies-literature
Project description:Lung microbiome ecosystem homeostasis in idiopathic pulmonary fibrosis (IPF) remains uncharacterized. The aims of this study were to identify unique microbial signatures of the lung microbiome and analyze microbial gene function in IPF patients. DNA isolated from BALF samples was obtained for high-throughput gene sequencing. Microbial metagenomic data were used for principal component analysis (PCA) and analyzed at different taxonomic levels. Shotgun metagenomic data were annotated using the KEGG database and were analyzed for functional and metabolic pathways. In this study, 17 IPF patients and 38 healthy subjects (smokers and non-smokers) were recruited. For the PCA, the first and the second principal component explained 16.3 and 13.4% of the overall variability, respectively. The β diversity of microbiome was reduced in the IPF group. Signature of IPF's microbes was enriched of Streptococcus, Pseudobutyrivibrio, and Anaerorhabdus. The translocation of lung microbiome was shown that 32.84% of them were from oral. After analysis of gene function, ABC transporter systems, biofilm formation, and two-component regulatory system were enriched in IPF patients' microbiome. Here we shown the microbiology characteristics in IPF patients. The microbiome may participate in altering internal conditions and involving in generating antibiotic resistance in IPF patients.
| S-EPMC6536613 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a group of common and lethal forms of idiopathic interstitial pulmonary disease. IPF is characterized by a progressive decline in lung function with a median survival of 2-3 years after diagnosis. Although the pathogenesis of the disease remains unknown, genetic predisposition could play a causal role in IPF. A set of genes have been identified as candidate genes of IPF in the past 20 years. However, the recent technological advances that allow for the analysis of millions of polymorphisms in different subjects have deepened the understanding of the genetic complexity of IPF susceptibility. Genome-wide association studies and whole-genome sequencing continue to reveal the genetic loci associated with IPF risk. In this review, we describe candidate genes on the basis of their functions and aim to gain a better understanding of the genetic basis of IPF. The discovered candidate genes may help to clarify pivotal aspects in the diagnosis, prognosis, and therapies of IPF.
| S-EPMC4745857 | biostudies-literature
Project description:Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host-microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.
| S-EPMC8779068 | biostudies-literature
Project description:Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) have been defined as events of clinically significant respiratory deterioration with an unidentifiable cause. They carry a significant mortality and morbidity and while their exact pathogenesis remains unclear, the possibility remains that hidden infection may play a role. The aim of this pilot study was to determine whether changes in the respiratory microbiota occur during an AE-IPF. Bacterial DNA was extracted from bronchoalveolar lavage from patients with stable IPF and those experiencing an AE-IPF. A hyper-variable region of the 16S ribosomal RNA gene (16S rRNA) was amplified, quantified and pyrosequenced. Culture independent techniques demonstrate AE-IPF is associated with an increased BAL bacterial burden compared to stable disease and highlight shifts in the composition of the respiratory microbiota during an AE-IPF.
| S-EPMC5286769 | biostudies-literature
Project description:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings. METHODS:Thirty-four subjects diagnosed with IPF were included in this analysis. The 16S rDNA was purified from bronchoalveolar lavage fluid obtained at the time of diagnosis and analyzed using next-generation sequencing techniques to characterize the bacterial communities. Furthermore, microbiomes from mice with bleomycin-induced lung fibrosis were analyzed. RESULTS:The most prevalent lung phyla were Firmicutes, Proteobacteria and Bacteroidetes. Decreased microbial diversity was found in patients with low forced vital capacity (FVC) and early mortality. Additionally, the diversity and relative abundance of Firmicutes, Streptococcaceae, and Veillonellaceae were significantly associated with FVC, 6-min walk distance, and serum surfactant protein D. Bleomycin-induced lung fibrosis resulted in decrease of diversity and alteration of microbiota in PCoA analysis. These results support the observations in human specimens. CONCLUSIONS:This study identified relationships between specific taxa in BALF and clinical findings, which were also supported by experiments in a mouse model. Our data suggest the possibility that loss of microbial diversity is associated with disease activities of IPF.
| S-EPMC6389110 | biostudies-literature