Different functional genes of upper airway microbiome associated with natural course of childhood asthma

AbstractThe airway microbiome has an important role in asthma pathophysiology. However, little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. Here we report that the microbiota’s dynamic patterns and compositions are related to asthma exacerbations. We collected nasal blow samples (n = 319) longitudinally during a clinical trial at 2 time-points within one year: randomization when asthma is under control, and at time of early loss of asthma control (yellow zone (YZ)). We report that participants whose microbiota was dominated by the commensal Corynebacterium + Dolosigranulum cluster at RD experience the lowest rates of YZs (p = 0.005) and have longer time to develop at least 2 episodes of YZ (p = 0.03). The airway microbiota have changed from randomization to YZ. A switch from the Corynebacterium + Dolosigranulum cluster at randomization to the Moraxella- cluster at YZ poses the highest risk of severe asthma exacerbation (p = 0.04). Corynebacterium’s relative abundance at YZ is inversely associated with severe exacerbation (p = 0.002).

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The Role of Upper Airway Microbiome in the Development of Adult Asthma

Immune Network ◽

10.4110/in.2021.21.e19 ◽

2021 ◽

Vol 21 (3) ◽

Author(s):

Purevsuren Losol ◽

Jun-Pyo Choi ◽

Sae-Hoon Kim ◽

Yoon-Seok Chang

Keyword(s):

Upper Airway ◽

Adult Asthma ◽

Airway Microbiome

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Fungal and bacterial microbiome dysbiosis and imbalance of trans-kingdom network in asthma

Clinical and Translational Allergy ◽

10.1186/s13601-020-00345-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Chunrong Huang ◽

Youchao Yu ◽

Wei Du ◽

Yahui Liu ◽

Ranran Dai ◽

...

Keyword(s):

High Throughput Sequencing ◽

Functional Genes ◽

Metagenomic Sequencing ◽

Bacterial Microbiota ◽

Α Diversity ◽

Asthma Patients ◽

The Status ◽

Airway Microbiome ◽

Bacterial Microbiome ◽

Asthma Group

Abstract Background Fungal and bacterial microbiota play an important role in development of asthma. We aim to characterize airway microbiome (mycobiome, bacteriome) and functional genes in asthmatics and controls. Methods Sputum microbiome of controls, untreated asthma patients and inhaled corticosteroid (ICS) receiving patients was detected using high throughput sequencing. Metagenomic sequencing was used to examine the functional genes of microbiome. Results 1. Mycobiome: α diversity was lower in untreated asthma group than that in controls. Mycobiome compositions differed among the three groups. Compared with controls, untreated asthma group has higher abundance of Wallemia, Mortierella and Fusarium. Compared with untreated asthma patients, ICS receiving patients has higher abundance of Fusarium and Mortierella, lower frequency of Wallemia, Alternaria and Aspergillus. 2. Bacteriome: α diversity was lower in untreated asthma group than that in controls. There are some overlaps of bacteriome compositions between controls and untreated asthma patients which were distinct from ICS receiving patients. Untreated asthma group has higher Streptococcus than controls. 3. Potential fungal and bacterial biomarkers of asthma: Trametes, Aspergillus, Streptococcus, Gemella, Neisseria, etc. 4. Correlation network: There are dense and homogenous correlations in controls but a dramatically unbalanced network in untreated asthma and ICS receiving patients, which suggested the existence of disease-specific inter-kingdom and intra-kingdom alterations. 5. Metagenomic analysis: functional pathways were associated with the status of asthma, microbiome and functional genes showed different correlations in different environment. Conclusion We showed mycobiome and bacteriome dysbiosis in asthma featured by alterations in biodiversity, community composition, inter-kingdom and intra-kingdom network. We also observed several functional genes associated with asthma.

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Evaluation of the upper airway microbiome and immune response with nasal epithelial lining fluid absorption and nasal washes

Scientific Reports ◽

10.1038/s41598-020-77289-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Meghan H. Shilts ◽

Christian Rosas-Salazar ◽

Christian E. Lynch ◽

Andrey Tovchigrechko ◽

Helen H. Boone ◽

...

Keyword(s):

Immune Response ◽

Quality Control ◽

Sampling Method ◽

Upper Airway ◽

Healthy Children ◽

Metagenomic Sequencing ◽

Epithelial Lining ◽

Epithelial Lining Fluid ◽

Immune Mediator ◽

Airway Microbiome

AbstractDespite being commonly used to collect upper airway epithelial lining fluid, nasal washes are poorly reproducible, not suitable for serial sampling, and limited by a dilution effect. In contrast, nasal filters lack these limitations and are an attractive alternative. To examine whether nasal filters are superior to nasal washes as a sampling method for the characterization of the upper airway microbiome and immune response, we collected paired nasal filters and washes from a group of 40 healthy children and adults. To characterize the upper airway microbiome, we used 16S ribosomal RNA and shotgun metagenomic sequencing. To characterize the immune response, we measured total protein using a BCA assay and 53 immune mediators using multiplex magnetic bead-based assays. We conducted statistical analyses to compare common microbial ecology indices and immune-mediator median fluorescence intensities (MFIs) between sample types. In general, nasal filters were more likely to pass quality control in both children and adults. There were no significant differences in microbiome community richness, α-diversity, or structure between pediatric samples types; however, these were all highly dissimilar between adult sample types. In addition, there were significant differences in the abundance of amplicon sequence variants between sample types in children and adults. In adults, total proteins were significantly higher in nasal filters than nasal washes; consequently, the immune-mediator MFIs were not well detected in nasal washes. Based on better quality control sequencing metrics and higher immunoassay sensitivity, our results suggest that nasal filters are a superior sampling method to characterize the upper airway microbiome and immune response in both children and adults.

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Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to Staphylococcus aureus Superinfection

mBio ◽

10.1128/mbio.01939-15 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 52

Author(s):

Paul J. Planet ◽

Dane Parker ◽

Taylor S. Cohen ◽

Hannah Smith ◽

Justinne D. Leon ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

Upper Airway ◽

Mutant Mice ◽

Type Iii ◽

Interferon Receptor ◽

Airway Microbiome ◽

Upper Respiratory ◽

Type Iii Interferon

ABSTRACT Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection with pathogens that colonize the upper respiratory tract such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae . A major component of the immune response to influenza virus is the production of type I and III interferons. Here we show that the immune response to infection with influenza virus causes an increase and restructuring of the upper respiratory microbiota in wild-type (WT) mice but not in Il28r −/− mutant mice lacking the receptor for type III interferon. Mice lacking the IL-28 receptor fail to induce STAT1 phosphorylation and expression of its regulator, SOCS1. Il28r −/− mutant mice have increased expression of interleukin-22 (IL-22), as well as Ngal and RegIIIγ, in the nasal cavity, the source of organisms that would be aspirated to cause pneumonia. Proteomic analysis reveals changes in several cytoskeletal proteins that contribute to barrier function in the nasal epithelium that may contribute to the effects of IL-28 signaling on the microbiota. The importance of the effects of IL-28 signaling in the pathogenesis of MRSA pneumonia after influenza virus infection was confirmed by showing that WT mice nasally colonized before or after influenza virus infection had significantly higher levels of infection in the upper airways, as well as significantly greater susceptibility to MRSA pneumonia than Il28r −/− mutant mice did. Our results suggest that activation of the type III interferon in response to influenza virus infection has a major effect in expanding the upper airway microbiome and increasing susceptibility to lower respiratory tract infection. IMPORTANCE S. aureus and influenza virus are important respiratory pathogens, and coinfection with these organisms is associated with significant morbidity and mortality. The ability of influenza virus to increase susceptibility to S. aureus infection is less well understood. We show here that influenza virus leads to a change in the upper airway microbiome in a type III interferon-dependent manner. Mice lacking the type III interferon receptor have altered STAT1 and IL-22 signaling. In coinfection studies, mice without the type III interferon receptor had significantly less nasal S. aureus colonization and subsequent pneumonia than infected WT mice did. This work demonstrates that type III interferons induced by influenza virus contribute to nasal colonization and pneumonia due to S. aureus superinfection.

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Host genetic variation in mucosal immunity pathways influences the upper airway microbiome

Microbiome ◽

10.1186/s40168-016-0227-5 ◽

2017 ◽

Vol 5 (1) ◽

Cited By ~ 31

Author(s):

Catherine Igartua ◽

Emily R. Davenport ◽

Yoav Gilad ◽

Dan L. Nicolae ◽

Jayant Pinto ◽

...

Keyword(s):

Genetic Variation ◽

Mucosal Immunity ◽

Upper Airway ◽

Airway Microbiome ◽

Host Genetic

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Corynebacterium Species Inhibit Streptococcus pneumoniae Colonization and Infection of the Mouse Airway

Frontiers in Microbiology ◽

10.3389/fmicb.2021.804935 ◽

2022 ◽

Vol 12 ◽

Author(s):

Kadi J. Horn ◽

Alexander C. Jaberi Vivar ◽

Vera Arenas ◽

Sameer Andani ◽

Edward N. Janoff ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Respiratory Health ◽

Upper Airway ◽

Inhibitory Effect ◽

Airway Microbiome ◽

The Stability ◽

Independent Effects ◽

The Impact

The stability and composition of the airway microbiome is an important determinant of respiratory health. Some airway bacteria are considered to be beneficial due to their potential to impede the acquisition and persistence of opportunistic bacterial pathogens such as Streptococcus pneumoniae. Among such organisms, the presence of Corynebacterium species correlates with reduced S. pneumoniae in both adults and children, in whom Corynebacterium abundance is predictive of S. pneumoniae infection risk. Previously, Corynebacterium accolens was shown to express a lipase which cleaves host lipids, resulting in the production of fatty acids that inhibit growth of S. pneumoniae in vitro. However, it was unclear whether this mechanism contributes to Corynebacterium-S. pneumoniae interactions in vivo. To address this question, we developed a mouse model for Corynebacterium colonization in which colonization with either C. accolens or another species, Corynebacterium amycolatum, significantly reduced S. pneumoniae acquisition in the upper airway and infection in the lung. Moreover, the lungs of co-infected mice had reduced pro-inflammatory cytokines and inflammatory myeloid cells, indicating resolution of infection-associated inflammation. The inhibitory effect of C. accolens on S. pneumoniae in vivo was mediated by lipase-dependent and independent effects, indicating that both this and other bacterial factors contribute to Corynebacterium-mediated protection in the airway. We also identified a previously uncharacterized bacterial lipase in C. amycolatum that is required for inhibition of S. pneumoniae growth in vitro. Together, these findings demonstrate the protective potential of airway Corynebacterium species and establish a new model for investigating the impact of commensal microbiota, such as Corynebacterium, on maintaining respiratory health.

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