Seasonal airway microbiome and transcriptome interactions promote childhood asthma exacerbations

McCauley, Kathryn; Flynn, Kaitlin J.; DiMassa, Vincent; LaMere, Brandon; Fadrosh, Douglas; Lynch, Kole; Gill, Michelle A.; Pongracic, Jacqueline A.; Hershey, Gurjit K. Khurana; Kercsmar, Carolyn M.; Liu, Andrew H.; Johnson, Christine Cole; Kim, Hae Jin; Kattan, Meyer; O’Connor, George T.; Bacharier, Leonard B.; Teach, Stephen J.; Gergen, Peter J.; Wheatley, Lisa M.; Togias, Alkis; LeBeau, Petra; Calatroni, Agustin; Presnell, Scott; Boushey, Homer A.; Busse, William W.; Gern, James E.; Jackson, Daniel J.; Altman, Matthew C.; Lynch, Susan V.

doi:10.1016/j.jaci.2022.01.020

Cited by 43 publications

(28 citation statements)

References 48 publications

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“…Transcriptomic studies conducted in the reviewed period highlight important hostmicrobiome interactions in the upper and lower airways and open new directions for future research. Although McCauley et al [114] found that the interaction of host gene expression levels and microbial networks in the upper airways promote AEs, the causative direction of those relationships is unclear. Still, they proposed several J Investig Allergol Clin Immunol 2023; Vol.…”

Section: Discussionmentioning

confidence: 99%

“…Two transcriptomic studies of AEs have been published in the reviewed period. One focused on the interaction of transcriptional and bacterial networks in nasal epithelium on the risk of AEs in children [114]. Specifically, the risk of AEs increased along with the expression of genes implicated in SMAD3-related cell differentiation in a context of high abundance of a bacterial network dominated by Veillonella, Streptococcus, Neisseria, and Haemophilus and/or reduced abundance of a bacterial network dominated Staphylococcus [114].…”

Section: Epigeneticsmentioning

confidence: 99%

“…One focused on the interaction of transcriptional and bacterial networks in nasal epithelium on the risk of AEs in children [114]. Specifically, the risk of AEs increased along with the expression of genes implicated in SMAD3-related cell differentiation in a context of high abundance of a bacterial network dominated by Veillonella, Streptococcus, Neisseria, and Haemophilus and/or reduced abundance of a bacterial network dominated Staphylococcus [114]. Another study aimed to understand the pathophysiological factors underlying frequent exacerbations using transcriptomic data from bronchial biopsies.…”

Section: Epigeneticsmentioning

confidence: 99%

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Asthma Exacerbations: The Genes Behind the Scenes

Luis¹,

Forno²,

Celedón³

et al. 2023

J Investig Allergol Clin

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The clinical and socioeconomic burden of asthma exacerbations (AEs) represents a major public health problem. In the last four years, there has been an increase in ethnic diversity in candidate-gene and genome-wide association studies (GWAS) of AEs, which in the latter case has led to the identification of novel genes and underlying pathobiological processes. Pharmacogenomics, admixture mapping analyses, and the combination of multiple “omic” layers have contributed to prioritizing genomic regions of interest and/or understanding the functional consequences of genetic variation. Despite this, the field still lags behind the genomics of asthma, where a vast compendium of genetic approaches has been used (e.g., gene-environment interactions, next-generation sequencing, or polygenic risk scores). Furthermore, the roles of the DNA methylome and histone modifications in AEs have been scarcely investigated, and microRNA findings remain to be validated in independent studies. Likewise, the most recent transcriptomic studies highlight the importance of host-airway microbiome interaction in the modulation of AEs risk. Leveraging -omics and deep-phenotyping data from sub-types or homogenous subgroups of patients will be crucial to overcome the inherent heterogeneity of AEs, and boost the identification of potential therapeutic targets and the implementation of precision medicine in clinical practice for AEs.

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Section: Discussionmentioning

confidence: 99%

Section: Epigeneticsmentioning

confidence: 99%

Section: Epigeneticsmentioning

confidence: 99%

See 1 more Smart Citation

Asthma Exacerbations: The Genes Behind the Scenes

Luis¹,

Forno²,

Celedón³

et al. 2023

J Investig Allergol Clin

View full text Add to dashboard Cite

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“…McCauley et al demonstrated that RV infection was more likely to occur in asthmatic children with Streoptococcus-species-dominated nasal airway microbiomes and that nasal microbiomes dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation [ 64 ]. In addition, a recent study indicated that specific networks of upper airway microbes (those possessing Streptococcus, Haemophilus, Neisseria, Prevotella, and other genera or those lacking Staphylococcus) that interacted with host transcriptional responses significantly increased the risk of subsequent exacerbation and that this relationship was also strongly dependent on season [ 65 ].…”

Section: Role Of Respiratory Viral Infection In Asthma Pathogenesismentioning

confidence: 99%

Viral Infection and Airway Epithelial Immunity in Asthma

Kim

2022

IJMS

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Viral respiratory tract infections are associated with asthma development and exacerbation in children and adults. In the course of immune responses to viruses, airway epithelial cells are the initial platform of innate immunity against viral invasion. Patients with severe asthma are more vulnerable than those with mild to moderate asthma to viral infections. Furthermore, in most cases, asthmatic patients tend to produce lower levels of antiviral cytokines than healthy subjects, such as interferons produced from immune effector cells and airway epithelial cells. The epithelial inflammasome appears to contribute to asthma exacerbation through overactivation, leading to self-damage, despite its naturally protective role against infectious pathogens. Given the mixed and complex immune responses in viral-infection-induced asthma exacerbation, this review examines the diverse roles of airway epithelial immunity and related potential therapeutic targets and discusses the mechanisms underlying the heterogeneous manifestations of asthma exacerbations.

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“…Although respiratory infections may not be the crucial triggers in BA, specific bacterial-host interactions may significantly increase the risk of BA exacerbations ( 33 ). Moreover, the differences in nasal bacteriome may serve as indicators of different BA phenotypes ( 34 ).…”

Section: Bacteriome Part Of the Respiratory Microbiomementioning

confidence: 99%

Human airway and lung microbiome at the crossroad of health and disease (Review)

et al. 2022

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The evolving field of the microbiome and microbiota has become a popular research topic. The human microbiome is defined as a new organ and is considered a living community of commensal, symbiotic and pathogenic microorganisms within a certain body space. The term 'microbiome' is used to define the entire genome of the microbiota. Bacteria, archaea, fungi, algae and small protists are all members of the microbiota, followed by phages, viruses, plasmids and mobile genetic elements. The composition, heterogeneity and dynamics of microbiomes in time and space, their stability and resistance, essential characteristics and key participants, as well as interactions within the microbiome and with the host, are crucial lines of investigation for the development of successful future diagnostics and therapies. Standardization of microbiome studies and harmonized comparable methodologies are required for the transfer of knowledge from fundamental science into the clinic. Human health is dependent on microbiomes and achieved by nurturing beneficial resident microorganisms and their interplay with the host. The present study reviewed scientific knowledge on the major components of the human respiratory microbiome, i.e. bacteria, viruses and fungi, their symbiotic and parasitic roles, and, also, major diseases of the human respiratory tract and their microbial etiology. Bidirectional relationships regulate microbial ecosystems and host susceptibility. Moreover, environmental insults render host tissues and microbiota disease-prone. The human respiratory microbiome reflects the ambient air microbiome. By understanding the human respiratory microbiome, potential therapeutic strategies may be proposed.

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Seasonal airway microbiome and transcriptome interactions promote childhood asthma exacerbations

Cited by 43 publications

References 48 publications

Asthma Exacerbations: The Genes Behind the Scenes

Asthma Exacerbations: The Genes Behind the Scenes

Viral Infection and Airway Epithelial Immunity in Asthma

Human airway and lung microbiome at the crossroad of health and disease (Review)

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