The Respiratory Microbiome In Idiopathic Pulmonary Fibrosis

Molyneaux, Philip L.; Russell, Anne Marie; Cox, Michael J.; Moffatt, Miriam F.; Cookson, William; Maher, Toby

doi:10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a5174

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…We used sequence-based culture-independent methodologies to quantify both the numbers of bacterial genomes and the community composition of specimens collected by bronchoalveolar lavage. Some of the results of these studies have been previously reported in the form of an abstract (18).…”

Section: Methodsmentioning

confidence: 96%

The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis

Molyneaux

Cox

Willis‐Owen

et al. 2014

Am J Respir Crit Care Med

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446

406

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Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause that leads to respiratory failure and death within 5 years of diagnosis. Overt respiratory infection and immunosuppression carry a high morbidity and mortality, and polymorphisms in genes related to epithelial integrity and host defense predispose to IPF.Objectives: To investigate the role of bacteria in the pathogenesis and progression of IPF. Methods:We prospectively enrolled patients diagnosed with IPF according to international criteria together with healthy smokers, nonsmokers, and subjects with moderate chronic obstructive pulmonary disease as control subjects. Subjects underwent bronchoalveolar lavage (BAL), from which genomic DNA was isolated. The V3-V5 region of the bacterial 16S rRNA gene was amplified, allowing quantification of bacterial load and identification of communities by 16S rRNA quantitative polymerase chain reaction and pyrosequencing.Measurements and Main Results: Sixty-five patients with IPF had double the burden of bacteria in BAL fluid compared with 44 control subjects. Baseline bacterial burden predicted the rate of decline in lung volume and risk of death and associated independently with the rs35705950 polymorphism of the MUC5B mucin gene, a proven host susceptibility factor for IPF. Sequencing yielded 912,883 high-quality reads from all subjects. We identified Haemophilus, Streptococcus, Neisseria, and Veillonella spp. to be more abundant in cases than control subjects. Regression analyses indicated that these specific operational taxonomic units as well as bacterial burden associated independently with IPF.

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Section: Methodsmentioning

confidence: 96%

The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis

Molyneaux

Cox

Willis‐Owen

et al. 2014

Am J Respir Crit Care Med

Self Cite

446

406

View full text Add to dashboard Cite

show abstract

“…To date, there has been no assessment of the role of the respiratory microbiome in the pathogenesis, progression or exacerbation of IPF. However, it is anticipated that the assessment of the lung microbiome in IPF will shed important light on the role played by bacterial colonisation of the lower airways in the development and progression of fibrosis [47].…”

Section: The Role Of Bacteria In the Pathogenesis Of Ipfmentioning

confidence: 99%

The role of infection in the pathogenesis of idiopathic pulmonary fibrosis

Molyneaux

Maher

2013

European Respiratory Review

146

112

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Idiopathic pulmonary fibrosis (IPF) is a progressive, and invariably fatal, condition that is believed to arise in genetically susceptible individuals as a consequence of an aberrant wound-healing response following repetitive alveolar injury. The exact triggers, which initiate the fibrotic process, remain unknown. Infectious agents, including both viruses and bacteria, have the capacity to cause alveolarepithelial cell injury and apoptosis. Relatively few studies have examined the role of infection in IPF. Those that have, point to viruses playing a key role as cofactors in the initiation and progression of IPF. There is also some evidence to suggest that viral infection may be responsible for a proportion of acute exacerbations of IPF. The role played by bacteria in the pathogenesis of IPF is less clear cut. Studies from other respiratory diseases suggest that alterations in the lung microbiome are associated with disease and that these changes influence disease behaviour. Emerging molecular microbiological techniques are making the study of microbial communities in the lung easier. It is hoped that by combining such techniques with the careful longitudinal phenotyping of patients with IPF, it will be possible to elucidate the role played by bacteria and viruses in the pathogenesis of the disease. If infection plays a causal role in IPF then it is possible that therapeutic strategies, utilising currently available antiviral or antibiotic drugs, may be effective in modifying the course of this devastating condition.@ERSpublications Understanding viral and bacterial involvement in IPF could help development of novel therapeutic approaches

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“…[ Molyneaux et al (2012). We then focus on analyzing genera from both phyla Bacteroidetes and Firmicutes given their important status in normal lungs (Cui et al, 2014).…”

Section: Simulation Resultsmentioning

confidence: 99%

Exact Tests of Zero Variance Component in Presence of Multiple Variance Components with Application to Longitudinal Microbiome Study

Zhai

Knox²,

Twigg

et al. 2018

Preprint

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Summary:In the metagenomics studies, testing the association of microbiome composition and clinical conditions translates to testing the nullity of variance components. Computationally efficient score tests have been the major tools. But they can only apply to the null hypothesis with a single variance component and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to solve the problems of (1) testing the association of the overall microbiome composition in a longitudinal design and (2) detecting the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of human immunodeficiency virus (HIV) infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed lights on the impact of All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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The Respiratory Microbiome In Idiopathic Pulmonary Fibrosis

Cited by 4 publications

References 12 publications

The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis

The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis

The role of infection in the pathogenesis of idiopathic pulmonary fibrosis

Exact Tests of Zero Variance Component in Presence of Multiple Variance Components with Application to Longitudinal Microbiome Study

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