scholarly journals The Role of Lower Airway Dysbiosis in Asthma: Dysbiosis and Asthma

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Junying Lu ◽  
Lingxin Xiong ◽  
Xiaohao Zhang ◽  
Zhongmin Liu ◽  
Shiji Wang ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Chronic Respiratory Disease ◽  
Lower Airway ◽  
Healthy Controls ◽  
Steroid Resistant ◽  
Lung Microbiome ◽  
Culture Independent ◽  
Airway Microbiome ◽  
New Evidence

With the development of culture-independent techniques, numerous studies have demonstrated that the lower airway is not sterile in health and harbors diverse microbial communities. Furthermore, new evidence suggests that there is a distinct lower airway microbiome in those with chronic respiratory disease. To understand the role of lower airway dysbiosis in the pathogenesis of asthma, in this article, we review the published reports about the lung microbiome of healthy controls, provide an outlook on the contribution of lower airway dysbiosis to asthma, especially steroid-resistant asthma, and discuss the potential therapies targeted for lower airway dysbiosis.

scholarly journals 3439 Role of the Airway Microbiome in Viral Bronchiolitis Associated Respiratory Failure

2019 ◽  
Vol 3 (s1) ◽  
pp. 20-20
Author(s):  
Emily Wasserman ◽  
Stefan Worgall ◽  
Anurag Sharma
Keyword(s):  
Respiratory Failure ◽  
Airway Hyperresponsiveness ◽  
Respiratory Status ◽  
Lung Microbiome ◽  
Rhinovirus Infection ◽  
Microbiome Profile ◽  
Airway Microbiome ◽  
Study Population ◽  
Tracheal Aspirates

OBJECTIVES/SPECIFIC AIMS: This study aims to determine if a bronchiolitis specific microbiome exists and how it evolves through disease course. Objective 1. Determine the microbiome profile of the airway in virus induced bronchiolitis-associated respiratory failure. Objective 2. Identify changes in the airway microbiome profile through the course of virus induced bronchiolitis associated respiratory failure, and the relationship between microbiome composition and clinical respiratory status. Objective 3. Determine the impact of rhinovirus infection on the lung and stool microbiome in a murine asthma model. METHODS/STUDY POPULATION: Objectives 1 &2: We are conducting a single-center prospective case-control study of patients admitted to the Komansky - Weill Cornell Pediatric Critical Care Unit. Infants less than two years of age with a diagnosis of bronchiolitis requiring intubation and mechanical ventilation are enrolled as subjects. Infants less than two years of age intubated and requiring mechanical ventilation without primary lung pathology are enrolled as controls. To evaluate our primary objective, tracheal aspirates will be collected from both subjects and controls on the day of intubation. We will perform 16s RNA sequencing on the tracheal aspirate samples and compare the resulting microbiomes. To evaluate secondary objective, we will collect tracheal aspirates of our study population on a daily basis and map the microbiome in parallel with objective measures of respiratory status including oxygen index and successful extubation. Both subjects and controls are being enrolled as a convenience sample. Objective 3: Mice, heterozygous for the sptlc2 gene (Spltc2 +/−) demonstrate reduced de-novo sphingolipids and increased airway hyperresponsiveness with methacholine challenge. Airway hyper-responsiveness is a cardinal feature of asthma. This airway hyperresponsiveness is exacerbated in the setting of rhinovirus (Figure 1). Using 16s sequencing, we will examine the lung microbiome of Sptlc2 +/− ad Sptlc2 +/+ at 1- and 7-days following rhinovirus infection. RESULTS/ANTICIPATED RESULTS: This clinical study is currently IRB approved and enrollment is ongoing. We have enrolled 12 subjects and 5 controls. Sample analysis will begin following the 2018-2019 respiratory season, with an anticipated cohort of 20 subjects and 20 controls. With regards to the murine studies, we have demonstrated that the lung microbiome of Sptlc2 +/− and Sptlc2 +/+ mice is similar at baseline (Figure 2) and remains similar following 1-day infection with rhinovirus. We do however, see a distinct change in the microbiome profile of the stool of Sptlc2 +/− mice following rhinovirus infection (Figure 3). Lung analysis at day 7 post infection is pending. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies will lay the groundwork for detailing the functional role of the airway microbiome in bronchiolitis, with the objective of developing new modalities for disease treatment and prevention. In addition our murine studies allow us to view the microbiome in the context of sphingolipid deficiency, providing a potential mechanistic link to rhinovirus and ORMDL3 associated asthma.

scholarly journals Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis

2007 ◽  
Vol 53 (9) ◽  
pp. 1609-1614 ◽  
Author(s):  
Xiao-Yan Zhong ◽  
Ines von Mühlenen ◽  
Ying Li ◽  
Anjeung Kang ◽  
Anurag Kumar Gupta ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Animal Experiments ◽  
Basic Research ◽  
Healthy Controls ◽  
Serum Samples ◽  
Cell Free Dna ◽  
Free Dna ◽  
New Evidence

Abstract Background: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). Methods: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharose™ bead adsorption of plasma and elution to isolate antibody-bound DNA. Results: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319–21 000) and in 26 RA patients 17 000 GE/mL plasma (2100–2 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700–239 000) and from RA patients 222 000 GE/mL (21 000–2 375 000, P = 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P = 0.001). The concentrations of DNA did not vary with the type of therapy patients received. Conclusions: These results provide new evidence for a role of cell-free DNA-antibody complexes in the etiology of RA, suggest new avenues for basic research, and may prove to be relevant to diagnosis and assessment of therapy.

scholarly journals Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ

2017 ◽  
Vol 3 (3) ◽  
pp. 00008-2017 ◽  
Author(s):  
Jing Wang ◽  
Melissa Lesko ◽  
Michelle H. Badri ◽  
Bianca C. Kapoor ◽  
Benjamin G. Wu ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lavage Fluid ◽  
Interferon Γ ◽  
Lower Airway ◽  
Novel Therapy ◽  
Lung Microbiome ◽  
Airway Microbiome ◽  
Ifn Γ ◽  
Cell Supernatant

Therapies targeting inflammation reveal inconsistent results in idiopathic pulmonary fibrosis (IPF). Aerosolised interferon (IFN)-γ has been proposed as a novel therapy. Changes in the host airway microbiome are associated with the inflammatory milieu and may be associated with disease progression. Here, we evaluate whether treatment with aerosolised IFN-γ in IPF impacts either the lower airway microbiome or the host immune phenotype.Patients with IPF who enrolled in an aerosolised IFN-γ trial underwent bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of bronchoalveolar lavage fluid (BALF) was used to evaluate the lung microbiome. Biomarkers were measured by Luminex assay in plasma, BALF and BAL cell supernatant. The compPLS framework was used to evaluate associations between taxa and biomarkers.IFN-γ treatment did not change α or β diversity of the lung microbiome and few taxonomic changes occurred. While none of the biomarkers changed in plasma, there was an increase in IFN-γ and a decrease in Fit-3 ligand, IFN-α2 and interleukin-5 in BAL cell supernatant, and a decrease in tumour necrosis factor-β in BALF. Multiple correlations between microbial taxa common to the oral mucosa and host inflammatory biomarkers were found.These data suggest that the lung microbiome is independently associated with the host immune tone and may have a potential mechanistic role in IPF.

scholarly journals The Role of the Lung’s Microbiome in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis

2019 ◽  
Vol 20 (22) ◽  
pp. 5618 ◽  
Author(s):  
Paolo Spagnolo ◽  
Philip L. Molyneaux ◽  
Nicol Bernardinello ◽  
Elisabetta Cocconcelli ◽  
Davide Biondini ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Potential Role ◽  
Usual Interstitial Pneumonia ◽  
Microbiological Analysis ◽  
Culture Methods ◽  
Lung Microbiome ◽  
Culture Independent ◽  
Radiological Patterns

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease that commonly affects older adults and is associated with the histopathological and/or radiological patterns of usual interstitial pneumonia (UIP). Despite significant advances in our understanding of disease pathobiology and natural history, what causes IPF remains unknown. A potential role for infection in the disease’s pathogenesis and progression or as a trigger of acute exacerbation has long been postulated, but initial studies based on traditional culture methods have yielded inconsistent results. The recent application to IPF of culture-independent techniques for microbiological analysis has revealed previously unappreciated alterations of the lung microbiome, as well as an increased bacterial burden in the bronchoalveolar lavage (BAL) of IPF patients, although correlation does not necessarily entail causation. In addition, the lung microbiome remains only partially characterized and further research should investigate organisms other than bacteria and viruses, including fungi. The clarification of the role of the microbiome in the pathogenesis and progression of IPF may potentially allow its manipulation, providing an opportunity for targeted therapeutic intervention.

scholarly journals Chronic Rhinosinusitis and the Evolving Understanding of Microbial Ecology in Chronic Inflammatory Mucosal Disease

2016 ◽  
Vol 30 (1) ◽  
pp. 321-348 ◽  
Author(s):  
Michael Hoggard ◽  
Brett Wagner Mackenzie ◽  
Ravi Jain ◽  
Michael W. Taylor ◽  
Kristi Biswas ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Chronic Rhinosinusitis ◽  
Inflammatory Diseases ◽  
Modern Technology ◽  
Molecular Techniques ◽  
Modern Culture ◽  
Culture Independent ◽  
New Perspective ◽  
Microbiological Research

SUMMARY Chronic rhinosinusitis (CRS) encompasses a heterogeneous group of debilitating chronic inflammatory sinonasal diseases. Despite considerable research, the etiology of CRS remains poorly understood, and debate on potential roles of microbial communities is unresolved. Modern culture-independent (molecular) techniques have vastly improved our understanding of the microbiology of the human body. Recent studies that better capture the full complexity of the microbial communities associated with CRS reintroduce the possible importance of the microbiota either as a direct driver of disease or as being potentially involved in its exacerbation. This review presents a comprehensive discussion of the current understanding of bacterial, fungal, and viral associations with CRS, with a specific focus on the transition to the new perspective offered in recent years by modern technology in microbiological research. Clinical implications of this new perspective, including the role of antimicrobials, are discussed in depth. While principally framed within the context of CRS, this discussion also provides an analogue for reframing our understanding of many similarly complex and poorly understood chronic inflammatory diseases for which roles of microbes have been suggested but specific mechanisms of disease remain unclear. Finally, further technological advancements on the horizon, and current pressing questions for CRS microbiological research, are considered.

The polymicrobial nature of airway infections in cystic fibrosis: Cangene Gold Medal LectureThis article is based on a presentation by Dr. Christopher Sibley at the 60th Annual Meeting of the Canadian Society of Microbiologists in Hamilton, Ontario, on 15 June 2010. Dr. Sibley was the recipient of the 2010 Cangene Gold Medal as the Canadian Graduate Student Microbiologist of the Year, an annual award sponsored by Cangene Corporation intended to recognize excellence in graduate research.

2011 ◽  
Vol 57 (2) ◽  
pp. 69-77 ◽  
Author(s):  
Christopher D. Sibley ◽  
Michael G. Surette
Keyword(s):  
Cystic Fibrosis ◽  
Microbial Communities ◽  
Gold Medal ◽  
Emergent Properties ◽  
Host Interactions ◽  
Airway Infections ◽  
Future Challenges ◽  
Culture Independent ◽  
Airway Microbiome ◽  
Dynamic Communities

Microbial communities characterize the airways of cystic fibrosis (CF) patients. Members of these diverse and dynamic communities can be thought of as pathogens, benign commensals, or synergens — organisms not considered pathogens in the traditional sense but with the capacity to alter the pathogenesis of the community through microbe–microbe or polymicrobe–host interactions. Very few bacterial pathogens have been implicated as clinically relevant in CF; however, the CF airway microbiome can be a reservoir of previously unrecognized but clinically relevant organisms. A combination of culture-dependent and culture-independent approaches provides a more comprehensive perspective of CF microbiology than either approach alone. Here we review these concepts, highlight the future challenges for CF microbiology, and discuss the implications for the management of CF airway infections. We suggest that the success of treatment interventions for chronic CF lung disease will rely on the context of the microbes within microbial communities. The microbiology of CF airways may serve as a model to investigate the emergent properties of other clinically relevant microbial communities in the human body.

scholarly journals The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Zhang ◽  
Zhenxing Zhu ◽  
Xu Zuo ◽  
He Pan ◽  
Yinuo Gu ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Haemophilus Influenzae ◽  
High Throughput Sequencing ◽  
Lower Airway ◽  
Upper Respiratory Tract ◽  
Asthmatic Patients ◽  
Corticosteroid Resistance ◽  
Asthma Patients ◽  
Airway Microbiome

Abstract Asthma is a complex heterogeneous disease. The neutrophilic subtypes of asthma are described as persistent, more severe and corticosteroid-resistant, with higher hospitalization and mortality rates, which seriously affect the lives of asthmatic patients. With the development of high-throughput sequencing technology, an increasing amount of evidence has shown that lower airway microbiome dysbiosis contributes to the exacerbation of asthma, especially neutrophilic asthma. Nontypeable Haemophilus influenzae is normally found in the upper respiratory tract of healthy adults and is one of the most common strains in the lower respiratory tract of neutrophilic asthma patients, in whom its presence is related to the occurrence of corticosteroid resistance. To understand the pathogenic mechanism by which nontypeable Haemophilus influenzae colonization leads to the progression of neutrophilic asthma, we reviewed the previous literature on nontypeable Haemophilus influenzae colonization and subsequent aggravation of neutrophilic asthma and corticosteroid resistance. We discussed nontypeable Haemophilus influenzae as a potential therapeutic target to prevent the progression of neutrophilic asthma.

scholarly journals Mucus, Microbiomes and Pulmonary Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 675
Author(s):  
Oliver W. Meldrum ◽  
Sanjay H. Chotirmall
Keyword(s):  
Pulmonary Disease ◽  
Microbial Population ◽  
Chronic Respiratory Disease ◽  
Mucus Layer ◽  
Disease States ◽  
Pulmonary Physiology ◽  
Microbial Dysbiosis ◽  
Lung Microbiome ◽  
Significant Fluctuation

The respiratory tract harbors a stable and diverse microbial population within an extracellular mucus layer. Mucus provides a formidable defense against infection and maintaining healthy mucus is essential to normal pulmonary physiology, promoting immune tolerance and facilitating a healthy, commensal lung microbiome that can be altered in association with chronic respiratory disease. How one maintains a specialized (healthy) microbiome that resists significant fluctuation remains unknown, although smoking, diet, antimicrobial therapy, and infection have all been observed to influence microbial lung homeostasis. In this review, we outline the specific role of polymerizing mucin, a key functional component of the mucus layer that changes during pulmonary disease. We discuss strategies by which mucin feed and spatial orientation directly influence microbial behavior and highlight how a compromised mucus layer gives rise to inflammation and microbial dysbiosis. This emerging field of respiratory research provides fresh opportunities to examine mucus, and its function as predictors of infection risk or disease progression and severity across a range of chronic pulmonary disease states and consider new perspectives in the development of mucolytic treatments.

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