The Fungal Airway Microbiome in Cystic Fibrosis and Bronchiectasis

Cuthbertson, Leah; Felton, Imogen; James, Phillip; Cox, Michael J.; Bilton, Diana; Schelenz, Silke; Loebinger, Michael R.; Cookson, William; Simmonds, Nicholas J.; Moffatt, Miriam F.

doi:10.2139/ssrn.3542180

Cited by 7 publications

(5 citation statements)

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“…The top 6 taxa that contributed to PCA clustering dissimilarity between infection outcome were determined. DESeq2 was used to establish the DAA of the ASVs that differed in relative abundance in samples collected at-infection based on eventual outcomes (Heirali et al, 2019;Cuthbertson et al, 2021). We found that Pseudomonas and Stenotrophomonas correlated with the difference in clustering in the persistent At samples whereas Fusobacterium, Neisseria, Prevotellamassilia, and Haemophilus were associated with the clustering difference in the transient group (Figure 4C).…”

Section: Microbiome Structure At Incident Acquisition As a Function O...mentioning

confidence: 96%

The airway microbiome of persons with cystic fibrosis correlates with acquisition and microbiological outcomes of incident Stenotrophomonas maltophilia infection

Bowron,

Acosta,

Thornton

et al. 2024

Front. Microbiol.

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RationaleChronic infection with Stenotrophomonas maltophilia in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of S. maltophilia incident infection and persistence in pwCF.MethodspwCF experiencing incident S. maltophilia infections attending the Calgary Adult CF Clinic from 2010–2018 were compared with S. maltophilia-negative sex, age (+/−2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) (n = 57), at (At) (n = 22), and after (Post) (n = 31) incident infection. We verified relative abundance data using S. maltophilia-specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis.ResultsTwenty-five pwCF with incident S. maltophilia (56% female, median 29 years, median FEV1 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident S. maltophilia infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls (n = 56) based on Shannon Diversity Index (SDI, p = 0.04) and clustered based on Aitchison distance (PERMANOVA, p = 0.01) prior to infection. At the time of incident S. maltophilia isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, p = 0.03) in those that ultimately developed persistent infection versus those that were transient. S. maltophilia abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative (p = 0.004) and absolute (p = 0.001). Furthermore, S. maltophilia abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively (p = 0.04) or absolute (p = 0.04), respectively.ConclusionMicrobial community composition of CF sputum associates with S. maltophilia infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk.

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Section: Microbiome Structure At Incident Acquisition As a Function O...mentioning

confidence: 96%

The airway microbiome of persons with cystic fibrosis correlates with acquisition and microbiological outcomes of incident Stenotrophomonas maltophilia infection

Bowron,

Acosta,

Thornton

et al. 2024

Front. Microbiol.

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“…A higher chance of Aspergillus fumigatus fungal colonization and an exacerbation of pre-existing bronchiectasis are linked to nontuberculous mycobacteria (NTM) infection (Kunst et al, 2006;Aksamit et al, 2017;Chotirmall and Martin-Gomez, 2018). A poor prognostic sign is the occurrence of fungal infections such as Candida, Penicillium, Cryptococcus, Clavispora, and Scedosporium, particularly when allergic bronchopulmonary aspergillosis (ABPA) develops (Chandrasekaran et al, 2018;Chotirmall and Martin-Gomez, 2018;Mac Aogaín et al, 2018;Mac Aogaín et al, 2019a;Cuthbertson et al, 2021).. Although the exact involvement of viruses in bronchiectasis is unknown, viruses such as influenza, rhinovirus, and coronavirus have been often found in individuals with bronchiectasis (Gao et al, 2015;Wurzel et al, 2016;Mitchell et al, 2018).…”

Section: Infection's Rolementioning

confidence: 99%

“…Fungal infections are still difficult to diagnose because of their low sensitivity and specificity, which can cause therapy delays and unfavorable results (Delhaes et al, 2019;Mac Aogaín et al, 2019b). A decreased fungal diversity has been reported in bronchiectasis associated with cystic fibrosis in comparison to non-CF bronchiectasis (Cuthbertson et al, 2021). When compared to healthy controls, the Cohort of Asian and Matched European Bronchiectasis (CAMEB), the primary study of the bronchiectasis mycobiome, revealed a higher abundance of potentially pathogenic fungi such as Aspergillus, Penicillium, and Cryptococcus.…”

Section: Mycobiommentioning

confidence: 99%

Lung microbiome: new insights into bronchiectasis’ outcome

Azoicai,

Lupu,

Alexoae

et al. 2024

Front. Cell. Infect. Microbiol.

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The present treatments for bronchiectasis, which is defined by pathological dilatation of the airways, are confined to symptom relief and minimizing exacerbations. The condition is becoming more common worldwide. Since the disease’s pathophysiology is not entirely well understood, developing novel treatments is critically important. The interplay of chronic infection, inflammation, and compromised mucociliary clearance, which results in structural alterations and the emergence of new infection, is most likely responsible for the progression of bronchiectasis. Other than treating bronchiectasis caused by cystic fibrosis, there are no approved treatments. Understanding the involvement of the microbiome in this disease is crucial, the microbiome is defined as the collective genetic material of all bacteria in an environment. In clinical practice, bacteria in the lungs have been studied using cultures; however, in recent years, researchers use next-generation sequencing methods, such as 16S rRNA sequencing. Although the microbiome in bronchiectasis has not been entirely investigated, what is known about it suggests that Haemophilus, Pseudomonas and Streptococcus dominate the lung bacterial ecosystems, they present significant intraindividual stability and interindividual heterogeneity. Pseudomonas and Haemophilus-dominated microbiomes have been linked to more severe diseases and frequent exacerbations, however additional research is required to fully comprehend the role of microbiome in the evolution of bronchiectasis. This review discusses recent findings on the lung microbiota and its association with bronchiectasis.

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“…The fungal microbiome of the CF respiratory tract has been investigated using culture-independent methods, including 18S rRNA and internal transcribed spacer sequencing methods [34–36,37 ▪▪ ,38]. Candida genus ( C. albicans , C. parapsilosis and C .…”

Section: Diagnostic Testing For Fungal Lung Disease In People With Cy...mentioning

confidence: 99%

“…Candida genus ( C. albicans , C. parapsilosis and C . dubliniensis ) is the most prevalent and abundant fungi identified in CF sputa across studies [35,36,37 ▪▪ ]. Candida species is a known microbe in the oral cavity.…”

Section: Diagnostic Testing For Fungal Lung Disease In People With Cy...mentioning

confidence: 99%

Progress and challenges in fungal lung disease in cystic fibrosis

Hong

2022

Current Opinion in Pulmonary Medicine

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Purpose of reviewThis review is an overview of the recent progress made for the diagnosis and understanding of fungal lung disease in people with cystic fibrosis (CF), with a focus on Aspergillus fumigatus, the most common filamentous fungus in the CF airway. Currently, the longstanding question of the clinical significance of Aspergillus fumigatus and other fungi in CF respiratory cultures, in the absence of allergy, remains. Clinical criteria and biomarkers are needed to classify fungal lung disease and determine who may warrant therapy.Recent findingsSeveral retrospective and prospective studies have described the prevalence of A. fumigatus and other fungi in the CF lung and factors contributing to the changes in fungal epidemiology. Selective fungus culture testing for the detection of fungi in CF sputa has been well studied, yet a standardized fungus culture protocol has yet to be defined. Culture-independent molecular studies and other fungal diagnostic testing have been conducted in the CF population, leading to efforts to better understand the clinical role of these tests. Recent works have aimed to determine whether chronic A. fumigatus colonization is associated with lung disease progression measured by FEV1 percentage predicted, structural lung disease, lung clearance index and respiratory quality-of-life. However, the existing knowledge gaps remain: definition of a fungal respiratory infection, the association between fungal infection and clinical outcomes, and indications for antifungal therapy.SummarySignificant progress has been made for the detection and diagnosis of fungal lung disease. Yet, the role and impact of A. fumigatus and other fungal infections on respiratory health in people with CF remains to be determined.

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The Fungal Airway Microbiome in Cystic Fibrosis and Bronchiectasis

Cited by 7 publications

References 0 publications

The airway microbiome of persons with cystic fibrosis correlates with acquisition and microbiological outcomes of incident Stenotrophomonas maltophilia infection

The airway microbiome of persons with cystic fibrosis correlates with acquisition and microbiological outcomes of incident Stenotrophomonas maltophilia infection

Lung microbiome: new insights into bronchiectasis’ outcome

Progress and challenges in fungal lung disease in cystic fibrosis

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