scholarly journals Temporal profiling of the bacterial and fungal communities in ΔF508 adult cysticfibrosis sputum

2014 ◽  
Author(s):  
Andrew Nelson ◽  
Audrey Perry ◽  
Christopher J Stewart ◽  
Clare V Lanyon ◽  
John D Perry ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bacterial Communities ◽  
Species Turnover ◽  
Bacterial Load ◽  
Clinical Status ◽  
Fungal Communities ◽  
Antibiotic Administration ◽  
Qpcr Analysis ◽  
Newcastle Upon Tyne ◽  
Antibiotic Perturbations

Aims: The purpose of this study was to analyse the bacterial and fungal turnover in the lungs of cystic fibrosis patients who were ΔF508 homo- and hetero-zygotes. Further to this we wanted to identify the effects that Intravenous (IV) antibiotic perturbations had on the community and most importantly, whether exacerbations in these patients could be attributed to microbial species or communities. Methods: A total of 149 samples were collected from 18 adult CF patients attending a clinic at the RVI hospital, Newcastle upon Tyne. The samples were subject to DNA extraction followed by bacterial and fungal community DGGE analysis as well as qPCR analysis of the bacterial load. Results: We have found that bacterial and fungal communities present in the CF lung are not different when patients are suffering an exacerbation. Further to this, we have found that bacterial communities in the CF lung are disturbed by IV antibiotic administration and cause increased species turnover. We have shown that fungal taxa are capable of chronically colonising the CF lung. Conclusions: Our study adds further evidence to the assertion that changes in bacterial communities are not the cause of CF exacerbations. However, we were able to demonstrate that acquisition of new bacterial taxa was strongly associated with exacerbations in one patient. This study is the first to illustrate that fungi can persist in the CF lung but are not associated with clinical status.

scholarly journals Temporal profiling of the bacterial and fungal communities in ΔF508 adult cysticfibrosis sputum

2014 ◽  
Author(s):  
Andrew Nelson ◽  
Audrey Perry ◽  
Christopher J Stewart ◽  
Clare V Lanyon ◽  
John D Perry ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bacterial Communities ◽  
Species Turnover ◽  
Bacterial Load ◽  
Clinical Status ◽  
Fungal Communities ◽  
Antibiotic Administration ◽  
Qpcr Analysis ◽  
Newcastle Upon Tyne ◽  
Antibiotic Perturbations

Aims: The purpose of this study was to analyse the bacterial and fungal turnover in the lungs of cystic fibrosis patients who were ΔF508 homo- and hetero-zygotes. Further to this we wanted to identify the effects that Intravenous (IV) antibiotic perturbations had on the community and most importantly, whether exacerbations in these patients could be attributed to microbial species or communities. Methods: A total of 149 samples were collected from 18 adult CF patients attending a clinic at the RVI hospital, Newcastle upon Tyne. The samples were subject to DNA extraction followed by bacterial and fungal community DGGE analysis as well as qPCR analysis of the bacterial load. Results: We have found that bacterial and fungal communities present in the CF lung are not different when patients are suffering an exacerbation. Further to this, we have found that bacterial communities in the CF lung are disturbed by IV antibiotic administration and cause increased species turnover. We have shown that fungal taxa are capable of chronically colonising the CF lung. Conclusions: Our study adds further evidence to the assertion that changes in bacterial communities are not the cause of CF exacerbations. However, we were able to demonstrate that acquisition of new bacterial taxa was strongly associated with exacerbations in one patient. This study is the first to illustrate that fungi can persist in the CF lung but are not associated with clinical status.

scholarly journals Divergence of bacterial communities in the lower airways of CF patients in early childhood

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0257838
Author(s):  
John B. O’Connor ◽  
Madison M. Mottlowitz ◽  
Brandie D. Wagner ◽  
Kathleen L. Boyne ◽  
Mark J. Stevens ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Early Childhood ◽  
Bacterial Communities ◽  
Quantitative Polymerase Chain Reaction ◽  
Bacterial Load ◽  
Negative Relationship ◽  
Lower Airway ◽  
Rrna Gene ◽  
Valuable Insight ◽  
Neutrophilic Inflammation

Rationale Chronic airway infection and inflammation resulting in progressive, obstructive lung disease is the leading cause of morbidity and mortality in cystic fibrosis. Understanding the lower airway microbiota across the ages can provide valuable insight and potential therapeutic targets. Objectives To characterize and compare the lower airway microbiota in cystic fibrosis and disease control subjects across the pediatric age spectrum. Methods Bronchoalveolar lavage fluid samples from 191 subjects (63 with cystic fibrosis) aged 0 to 21 years were collected along with relevant clinical data. We measured total bacterial load using quantitative polymerase chain reaction and performed 16S rRNA gene sequencing to characterize bacterial communities with species-level sensitivity for select genera. Clinical comparisons were investigated. Measurements and main results Cystic fibrosis samples had higher total bacterial load and lower microbial diversity, with a divergence from disease controls around 2–5 years of age, as well as higher neutrophilic inflammation relative to bacterial burden. Cystic fibrosis samples had increased abundance of traditional cystic fibrosis pathogens and decreased abundance of the Streptococcus mitis species group in older subjects. Interestingly, increased diversity in the heterogeneous disease controls was independent of diagnosis and indication. Sequencing was more sensitive than culture, and antibiotic exposure was more common in disease controls, which showed a negative relationship with load and neutrophilic inflammation. Conclusions Analysis of lower airway samples from people with cystic fibrosis and disease controls across the ages revealed key differences in airway microbiota and inflammation. The divergence in subjects during early childhood may represent a window of opportunity for intervention and additional study.

Respiratory and Gut Microbiota of Children with Cystic Fibrosis: A Pilot Study

2021 ◽  
Vol 5 (1) ◽  
pp. 1-7
Author(s):  
Jannaina Ferreira de Melo Vasco ◽  
Carlos A. Riedi ◽  
Camila Marconi ◽  
Keite S. Nogueira ◽  
Luiza Souza Rodrigues ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pilot Study ◽  
Gut Microbiota ◽  
Ribosomal Rna ◽  
Bacterial Communities ◽  
Clinical Presentation ◽  
Clinical Status ◽  
Microbial Composition ◽  
Bioinformatics Analyses ◽  
Stool Samples

Differences in the clinical presentation of cystic fibrosis (CF) may be due to microbiota components and their relationship with the host’s immune system. In this pilot study, we aimed to investigate the composition of the respiratory and gut microbiota of a cohort of clinically stable children with CF, homozygous for the p.Phe508del mutation. Oropharyngeal swabs and stool samples were obtained from these children attending the CF referral clinics at the Hospital of Clinics, Federal University Paraná (CHC – UFPR). Oropharyngeal and gut microbiota were assessed by V3-V4 sequencing of the 16S ribosomal RNA, and bioinformatics analyses were performed using a proprietary pipeline. We identified a total of 456 bacterial taxa belonging to 164 genera, of which 65 (39.6 %) were common to both the respiratory and gastrointestinal tracts. Taxa from eight genera dominated more than 75 % of the microbial composition of both the niches. Among these dominant taxa, only Prevotella spp. were common to both the sites. Overall, the respiratory and gut microbiota were homogeneous among all the patients. Longitudinal studies targeting a larger cohort are important for an improved understanding of how the composition of bacterial communities is related to changes in the clinical status of CF

scholarly journals Inflammation in children with cystic fibrosis: contribution of bacterial production of long-chain fatty acids

2021 ◽  
Author(s):  
Erin Felton ◽  
Aszia Burrell ◽  
Hollis Chaney ◽  
Iman Sami ◽  
Anastassios C. Koumbourlis ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Fatty Acid ◽  
Antibiotic Treatment ◽  
Bacterial Production ◽  
Clinical Status ◽  
Achromobacter Xylosoxidans ◽  
List Type ◽  
Future Studies ◽  
Long Chain

Abstract Background Cystic fibrosis (CF) affects >70,000 people worldwide, yet the microbiologic trigger for pulmonary exacerbations (PExs) remains unknown. The objective of this study was to identify changes in bacterial metabolic pathways associated with clinical status. Methods Respiratory samples were collected at hospital admission for PEx, end of intravenous (IV) antibiotic treatment, and follow-up from 27 hospitalized children with CF. Bacterial DNA was extracted and shotgun DNA sequencing was performed. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance, while DESeq2 was used to evaluate differential abundance based on clinical status. Results The mean age of study participants was 10 years; 85% received combination IV antibiotic therapy (beta-lactam plus a second agent). Long-chain fatty acid (LCFA) biosynthesis pathways were upregulated in follow-up samples compared to end of treatment: gondoate (p = 0.012), oleate (p = 0.048), palmitoleate (p = 0.043), and pathways of fatty acid elongation (p = 0.012). Achromobacter xylosoxidans and Escherichia sp. were also more prevalent in follow-up compared to PEx (p < 0.001). Conclusions LCFAs may be associated with persistent infection of opportunistic pathogens. Future studies should more closely investigate the role of LCFA production by lung bacteria in the transition from baseline wellness to PEx in persons with CF. Impact Increased levels of LCFAs are found after IV antibiotic treatment in persons with CF. LCFAs have previously been associated with increased lung inflammation in asthma. This is the first report of LCFAs in the airway of persons with CF. This research provides support that bacterial production of LCFAs may be a contributor to inflammation in persons with CF. Future studies should evaluate LCFAs as predictors of future PExs.

scholarly journals 80 Comparison of the bacterial communities sampled from the healthy and the cystic fibrosis lung

2007 ◽  
Vol 6 ◽  
pp. S20
Author(s):  
F.A. Stressmann ◽  
G.B. Rogers ◽  
A.K. Lilley ◽  
M.P. Carroll ◽  
T. Daniels ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bacterial Communities ◽  
Cystic Fibrosis Lung

Using chest CT scan and unsupervised machine learning for predicting and evaluating response to lumacaftor-ivacaftor in people with cystic fibrosis

2021 ◽  
pp. 2101344
Author(s):  
Alienor Campredon ◽  
Enzo Battistella ◽  
Clémence Martin ◽  
Isabelle Durieu ◽  
Laurent Mely ◽  
...  
Keyword(s):  
Machine Learning ◽  
Cystic Fibrosis ◽  
Ct Scan ◽  
Structural Changes ◽  
Clinical Status ◽  
Chest Ct ◽  
Ct Scans ◽  
Wall Thickening ◽  
Unsupervised Machine Learning ◽  
One Year

ObjectivesLumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). This study aimed to assess lung structural changes after one year of lumacaftor-ivacaftor treatment, and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor.MethodsAdolescents and adults with CF from the French multicenter real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pretherapeutic and follow-up chest computed tomography (CT)-scans available. CT scans were visually scored using a modified Bhalla score. A k-mean clustering method was performed based on 120 radiomics features extracted from unenhanced pretherapeutic chest CT scans.ResultsA total of 283 patients were included. The Bhalla score significantly decreased after 1 year of lumacaftor-ivacaftor (−1.40±1.53 points compared with pretherapeutic CT; p<0.001). This finding was related to a significant decrease in mucus plugging (−0.35±0.62 points; p<0.001), bronchial wall thickening (−0.24±0.52 points; p<0.001) and parenchymal consolidations (−0.23±0.51 points; p<0.001). Cluster analysis identified 3 morphological clusters. Patients from cluster C were more likely to experience an increase in percent predicted forced expiratory volume in 1 sec (ppFEV1) ≥5 under lumacaftor–ivacaftor than those in the other clusters (54% of responders versus 32% and 33%; p=0.01).ConclusionOne year treatment with lumacaftor-ivacaftor was associated with a significant visual improvement of bronchial disease on chest CT. Radiomics features on pretherapeutic CT scan may help in predicting lung function response under lumacaftor-ivacaftor.

scholarly journals Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242945
Author(s):  
Graham Devereux ◽  
Danielle Wrolstad ◽  
Stephen J. Bourke ◽  
Cori L. Daines ◽  
Simon Doe ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cystic Fibrosis ◽  
Randomized Clinical Trial ◽  
Outcome Measures ◽  
Leukocyte Count ◽  
Bacterial Load ◽  
Adjunct Treatment ◽  
Dosing Regimens ◽  
Pulmonary Exacerbations ◽  
Blood Leukocyte

Background Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints? Methods and findings Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire–Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049. Conclusion In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures. Clinical trial registration NCT03000348; www.clinicaltrials.gov.

scholarly journals Unsupervised Phenotypic Clustering for Determining Clinical Status in Children with Cystic Fibrosis

2021 ◽  
pp. 2002881
Author(s):  
Nicole Filipow ◽  
Gwyneth Davies ◽  
Eleanor Main ◽  
Neil J. Sebire ◽  
Colin Wallis ◽  
...  
Keyword(s):  
Machine Learning ◽  
Cystic Fibrosis ◽  
Lung Function ◽  
Disease Severity ◽  
Learning Algorithm ◽  
Severe Disease ◽  
Clinical Status ◽  
Oral Antibiotics ◽  
Multisystem Disease ◽  
Street Hospital

BackgroundCystic Fibrosis (CF) is a multisystem disease in which assessing disease severity based on lung function alone may not be appropriate. The aim of the study was to develop a comprehensive machine-learning algorithm to assess clinical status independent of lung function in children.MethodsA comprehensive prospectively collected clinical database (Toronto, Canada) was used to apply unsupervised cluster analysis. The defined clusters were then compared by current and future lung function, risk of future hospitalisation, and risk of future pulmonary exacerbation (PEx) treated with oral antibiotics. A K-Nearest Neighbours (KNN) algorithm was used to prospectively assign clusters. The methods were validated in a paediatric clinical CF dataset from Great Ormond Street Hospital (GOSH).ResultsThe optimal cluster model identified four (A-D) phenotypic clusters based on 12 200 encounters from 530 individuals. Two clusters (A,B) consistent with mild disease were identified with high FEV1, and low risk of both hospitalisation and PEx treated with oral antibiotics. Two clusters (C,D) consistent with severe disease were also identified with low FEV1. Cluster D had the shortest time to both hospitalisation and PEx treated with oral antibiotics. The outcomes were consistent in 3124 encounters from 171 children at GOSH. The KNN cluster allocation error rate was low, at 2.5% (Toronto), and 3.5% (GOSH).ConclusionMachine learning derived phenotypic clusters can predict disease severity independent of lung function and could be used in conjunction with functional measures to predict future disease trajectories in CF patients.

scholarly journals Ecological networks reveal contrasting patterns of bacterial and fungal communities in glacier-fed streams in Central Asia

2019 ◽  
Author(s):  
Ze Ren ◽  
Hongkai Gao
Keyword(s):  
Bacterial Community ◽  
Microbial Communities ◽  
Central Asia ◽  
Fungal Community ◽  
Bacterial Communities ◽  
Beta Diversity ◽  
Hydrological Modeling ◽  
Alpha Diversity ◽  
Environmental Variation ◽  
Fungal Communities

Bacterial and fungal communities in biofilms are important components in driving biogeochemical processes in stream ecosystems. Previous studies have well documented the patterns of bacterial alpha diversity in stream biofilms in glacier-fed streams, where, however, beta diversity of the microbial communities has received much less attention especially considering both bacterial and fungal communities. A focus on beta diversity can provide insights into the mechanisms driving community changes associated to large environmental fluctuations and disturbances, such as in glacier-fed streams. Moreover, modularity of co-occurrence networks can reveal more ecological and evolutionary properties of microbial communities beyond taxonomic groups. Here, integrating beta diversity and co-occurrence approach, we explored the network topology and modularity of the bacterial and fungal communities with consideration of environmental variation in glacier-fed streams in Central Asia. Combining results from hydrological modeling and normalized difference of vegetation index, this study highlighted that hydrological variables and vegetation status are major variables determining the environmental heterogeneity of glacier-fed streams. Bacterial communities formed a more complex and connected network, while the fungal communities formed a more clustered network. Moreover, the strong interrelations among the taxonomic dissimilarities of bacterial community and modules suggest they had common processes in driving diversity and taxonomic compositions across the heterogeneous environment. In contrast, fungal community and modules generally showed distinct driving processes to each other. Moreover, bacterial and fungal communities also had different driving processes. Furthermore, the variation of bacterial community and modules were strongly correlated with hydrological properties and vegetation status but not with nutrients, while fungal community and modules (except one module) were not associated with environmental variation. Our results suggest that bacterial and fungal communities had distinct mechanisms in structuring microbial networks, and environmental variation had strong influences on bacterial communities but not on fungal communities. The fungal communities have unique assembly mechanisms and physiological properties which might lead to their insensitive responses to environmental variations compared to bacterial communities. Overall, beyond alpha diversity in previous studies, these results add our knowledge that bacterial and fungal communities have contrasting assembly mechanisms and respond differently to environmental variation in glacier-fed streams.

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