The impact of azithromycin therapy on the airway microbiota in asthma.
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ABSTRACT:
SUBMITTER: Slater M
PROVIDER: S-EPMC4078717 | biostudies-literature | 2014 Jul
REPOSITORIES: biostudies-literature
Publications
The impact of azithromycin therapy on the airway microbiota in asthma.
Slater Mariel M Rivett Damian W DW Williams Lisa L Martin Matthew M Harrison Tim T Sayers Ian I Bruce Kenneth D KD Shaw Dominick D
Thorax 20131128 7
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Project description:Asthma is a chronic respiratory disease with increasing global prevalence, often linked to disrupted airway microbiota. Azithromycin has shown promise in asthma treatment, but whether its effect is owing to its antimicrobial capacity remains largely unknown. A house dust mite (HDM)-induced asthmatic mouse model was used to evaluate the effects of azithromycin on airway inflammation and microbiota. Mice were divided into control, HDM-induced asthma, HDM + azithromycin, and azithromycin-alone groups. Airway microbiota was analyzed using 16S rRNA sequencing, and metabolomic profiles were assessed via liquid chromatography-tandem mass spectrometry. Azithromycin alleviated type 2 airway inflammation in HDM-induced asthma, restoring microbiota diversity by modulating specific genera, including Streptococcus, Staphylococcus, Ruminococcus, Coprococcus, Bifidobacterium, etc. Combination analysis with metabolomics revealed that azithromycin significantly regulated airway microbiota-associated sphingomyelin metabolism. Azithromycin's therapeutic effects in asthma are associated with its ability to regulate airway microbiota and its associated sphingomyelin metabolism, highlighting the potential for microbiota-targeted therapies in asthma.IMPORTANCEAsthma, a prevalent chronic respiratory condition, poses a significant global health challenge due to its increasing prevalence and associated morbidity. The role of airway microbiota in asthma pathogenesis is gaining attention, with evidence suggesting that disruptions in this microbial community contribute to disease severity. Our study investigates the impact of azithromycin, a macrolide antibiotic, on airway inflammation and microbiota in a mouse model of asthma. The findings reveal that azithromycin not only alleviates airway inflammation but also restores microbiota diversity and modulates microbiota-associated sphingomyelin metabolism. This research underscores the potential of microbiota-targeted therapies in asthma management, offering a novel therapeutic strategy that could improve patient outcomes and reduce the healthcare burden associated with asthma.
| S-EPMC11878009 | biostudies-literature
Project description:BackgroundHigh bacterial burden in the lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin (AZT) is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases, and observational studies have shown a positive effect of AZT on mortality and hospitalisation rate in IPF. However, the effect of AZT on the lung microbiota in IPF remains unknown.MethodsWe sought to determine the impact of a 3-month course of AZT on the lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomised controlled crossover trial of oral AZT 500 mg 3 times per week. 16S rRNA gene amplicon sequencing and quantitative PCR (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARGs) were assessed using real-time qPCR.ResultsAZT significantly decreased community diversity with a stronger and more persistent effect in the lower airways (sputum). AZT treatment altered the temporal kinetics of the upper (oropharyngeal swab) and lower airway microbiota, increasing community similarity between the two sites for 1 month after macrolide cessation. Patients with an increase in ARG carriage had lower bacterial density and enrichment of the genus Streptococcus. In contrast, patients with more stable ARG carriage had higher bacterial density and enrichment in Prevotella.ConclusionsAZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.
| S-EPMC10204823 | biostudies-literature
Project description:Individual studies have suggested that upper airway dysbiosis may be associated with asthma or its severity. We aimed to systematically review studies that evaluated upper airway bacterial microbiota in relation to asthma, compared to nonasthmatic controls. Searches used MEDLINE, Embase, and Web of Science Core Collection. Eligible studies included association between asthma and upper airway dysbiosis; assessment of composition and diversity of upper airway microbiota using 16S rRNA or metagenomic sequencing; upper airway samples from nose, nasopharynx, oropharynx or hypopharynx. Study quality was assessed and rated using the Newcastle-Ottawa scale. A total of 249 publications were identified; 17 in the final analysis (13 childhood asthma and 4 adult asthma). Microbiome richness was measured in 6 studies, species diversity in 12, and bacterial composition in 17. The quality of evidence was good and fair. The alpha-diversity was found to be higher in younger children with wheezing and asthma, while it was lower when asthmatic children had rhinitis or mite sensitization. In children, Proteobacteria and Firmicutes were higher in asthmatics compared to controls (7 studies), and Moraxella, Streptococcus, and Haemophilus were predominant in the bacterial community. In pooled analysis, nasal Streptococcus colonization was associated with the presence of wheezing at age 5 (p = 0.04). In adult patients with asthma, the abundance of Proteobacteria was elevated in the upper respiratory tract (3 studies). Nasal colonization of Corynebacterium was lower in asthmatics (2 studies). This study demonstrates the potential relationships between asthma and specific bacterial colonization in the upper airway in adult and children with asthma.
| S-EPMC9353206 | biostudies-literature
Project description:BackgroundThe proliferation of airway smooth muscle cells (ASMCs) is a key feature of airway remodeling in asthma. Azithromycin (AZM) has been shown to decrease bronchial hyperresponsiveness and airway inflammation in asthmatics; however, the role of AZM in ASMC proliferation remains unclear. Thus, we investigated the effect of AZM on ASMC proliferation in a rat model of experimental asthma.MethodsWe isolated ASMCs from rats sensitized and challenged by ovabulmin (OVA), and then treated with different concentrations of AZM. Cytotoxicity of ASMC was evaluated by Cell Counting Kit-8 (CCK-8) assay, morphological change was examined with laser confocal microscope after Annexin V/propidium iodide (PI) double staining, mitochondrial membrane potential was determined with JC-1 staining, and the expression of cytochrome C was examined by western blot.ResultsThe relative surface areas of airway wall and smooth muscle layers in OVA-sensitized rats were significantly increased compared to those in the control group. Furthermore, in OVA-sensitized rats, the mitochondrial membrane potential of ASMC was higher, while the expression of mitochondria cytochrome C was lower compared to that in control rats. After AZM treatment, ASMC apoptosis was increased, mitochondrial membrane potential reduced, and the protein level of cytosolic cytochrome C was increased.ConclusionsThis study demonstrated that AZM increased the apoptosis of ASMCs through a mitochondrial pathway, which might play an important role in ASMs proliferation during asthmatic remodeling.
| S-EPMC8350718 | biostudies-literature
Project description:Culture techniques have associated colonization with pathogenic bacteria in the airways of neonates with later risk of childhood asthma, whereas more recent studies utilizing sequencing techniques have shown the same phenomenon with specific anaerobic taxa. Here, we analyze nasopharyngeal swabs from 1 month neonates in the COPSAC2000 prospective birth cohort by 16S rRNA gene sequencing of the V3-V4 region in relation to asthma risk throughout childhood. Results are compared with previous culture results from hypopharyngeal aspirates from the same cohort and with hypopharyngeal sequencing data from the later COPSAC2010 cohort. Nasopharyngeal relative abundance values of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are associated with the same species in the hypopharyngeal cultures. A combined pathogen score of these bacteria's abundance values is associated with persistent wheeze/asthma by age 7. No other taxa are associated. Compared to the hypopharyngeal aspirates from the COPSAC2010 cohort, the anaerobes Veillonella and Prevotella, which have previously been implicated in asthma development, are less commonly detected in the COPSAC2000 nasopharyngeal samples, but correlate with the pathogen score, hinting at latent community structures that bridge current and previous results. These findings have implications for future asthma prevention efforts.
| S-EPMC10589220 | biostudies-literature
Project description:BackgroundAsthma and obesity are both complex conditions characterized by chronic inflammation, and obesity-related severe asthma has been associated with differences in the microbiome. However, whether the airway microbiome and microbiota-immune response relationships differ between obese persons with or without nonsevere asthma is unestablished.ObjectiveWe compared the airway microbiome and microbiota-immune mediator relationships between obese and nonobese subjects, with and without mild-moderate asthma.MethodsWe performed cross-sectional analyses of the airway (induced sputum) microbiome and cytokine profiles from blood and sputum using 16S ribosomal RNA gene and internal transcribed spacer region sequencing to profile bacteria and fungi, and multiplex immunoassays. Analysis tools included QIIME 2, linear discriminant analysis effect size (aka LEfSe), Piphillin, and Sparse inverse covariance estimation for ecological association inference (aka SPIEC-EASI).ResultsObesity, irrespective of asthma status, was associated with significant differences in sputum bacterial community structure and composition (unweighted UniFrac permutational analysis of variance, P = .02), including a higher relative abundance of Prevotella, Gemella, and Streptococcus species. Among subjects with asthma, additional differences in sputum bacterial composition and fungal richness were identified between obese and nonobese individuals. Correlation network analyses demonstrated differences between obese and nonobese asthma in relationships between cytokine mediators, and these together with specific airway bacteria involving blood PAI-1, sputum IL-1β, GM-CSF, IL-8, TNF-α, and several Prevotella species.ConclusionObesity itself is associated with an altered sputum microbiome, which further differs in those with mild-moderate asthma. The distinct differences in airway microbiota and immune marker relationships in obese asthma suggest potential involvement of airway microbes that may affect mechanisms or outcomes of obese asthma.
| S-EPMC10566565 | biostudies-literature
Project description:BackgroundImprovement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present.ObjectiveWe sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria.MethodsIn this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements.ResultsCompared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness.ConclusionThe composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.
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Project description: Not available
| S-EPMC5056860 | biostudies-literature
Project description:Asthma is believed to arise through early life aberrant immune development in response to environmental exposures that may influence the airway microbiota. Here, we examine the airway microbiota during the first three months of life by 16S rRNA gene amplicon sequencing in the population-based Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort consisting of 700 children monitored for the development of asthma since birth. Microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at age one month are associated with asthma by age 6 years, both individually and with additional taxa in a multivariable model. Higher relative abundance of these bacteria is furthermore associated with an airway immune profile dominated by reduced TNF-α and IL-1β and increased CCL2 and CCL17, which itself is an independent predictor for asthma. These findings suggest a mechanism of microbiota-immune interactions in early infancy that predisposes to childhood asthma.
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Project description:BackgroundCharacteristics of airway microbiota might influence asthma status or asthma phenotype. Identifying the airway microbiome can help to investigate its role in the development of asthma phenotypes or small airway function.MethodsBacterial microbiota profiles were analyzed in induced sputum from 31 asthma patients and 12 healthy individuals from Beijing, China. Associations between small airway function and airway microbiomes were examined.ResultsComposition of sputum microbiota significantly changed with small airway function in asthma patients. Two microbiome-driven clusters were identified and characterized by small airway function and taxa that had linear relationship with small airway functions were identified.ConclusionsOur findings confirm that airway microbiota was associated with small airway function in asthma patients.
| S-EPMC9837891 | biostudies-literature