scholarly journals Azithromycin and the microbiota of cystic fibrosis sputum

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nicole Acosta ◽  
Christina S. Thornton ◽  
Michael G. Surette ◽  
Ranjani Somayaji ◽  
Laura Rossi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Community Structure ◽  
Microbial Community ◽  
Lung Function ◽  
Rrna Gene ◽  
Lung Function Decline ◽  
Disease Pathogenesis ◽  
Cystic Fibrosis Sputum ◽  
Clustering Effect ◽  
The 16S Rrna Gene

Abstract Background Azithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis – we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure. Results Drawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders – demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas. Conclusions Azithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.

scholarly journals Refinement of metabolite detection in cystic fibrosis sputum reveals heme correlates with lung function decline

PLoS ONE ◽  
2019 ◽  
Vol 14 (12) ◽  
pp. e0226578 ◽  
Author(s):  
Nathaniel R. Glasser ◽  
Ryan C. Hunter ◽  
Theodore G. Liou ◽  
Dianne K. Newman ◽  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Lung Function Decline ◽  
Cystic Fibrosis Sputum ◽  
Metabolite Detection

scholarly journals A Volatile and Dynamic Longitudinal Microbiome Is Associated With Less Reduction in Lung Function in Adolescents With Cystic Fibrosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Marisa I. Metzger ◽  
Simon Y. Graeber ◽  
Mirjam Stahl ◽  
Olaf Sommerburg ◽  
Marcus A. Mall ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Contributing Factors ◽  
Lung Function Decline ◽  
Cross Sectional ◽  
Lung Microbiome ◽  
The Stability ◽  
The Individual

Progressive impairment in lung function caused by chronic polymicrobial airway infection remains the major cause of death in patients with cystic fibrosis (CF). Cross-sectional studies suggest an association between lung function decline and specific lung microbiome ecotypes. However, longitudinal studies on the stability of the airway microbiome are missing for adolescents with CF constituting the age group showing the highest rate of decline in lung function. In this study, we analyzed longitudinal lung function data and sputum samples collected over a period of 3 to 5 years from 12 adolescents with CF. The sputum microbiome was analyzed using 16S rRNA gene sequencing. Our results indicate that the individual course of the lung microbiome is associated with longitudinal lung function. In our cohort, patients with a dynamic, diverse microbiome showed a slower decline of lung function measured by FEV1% predicted, whereas a more stable and less diverse lung microbiome was related to worse outcomes. Specifically, a higher abundance of the phyla Bacteroidetes and Firmicutes was linked to a better clinical outcome, while Proteobacteria were correlated with a decline in FEV1% predicted. Our study indicates that the stability and diversity of the lung microbiome and the abundance of Bacteroidetes and Firmicutes are associated with the lung function decline and are one of the contributing factors to the disease severity.

scholarly journals Cytometric fingerprints of gut microbiota predict Crohn’s disease state

2019 ◽  
Author(s):  
Peter Rubbens ◽  
Ruben Props ◽  
Frederiek-Maarten Kerckhof ◽  
Nico Boon ◽  
Willem Waegeman
Keyword(s):  
Flow Cytometry ◽  
Crohn’S Disease ◽  
Community Structure ◽  
Microbial Community ◽  
Crohn's Disease ◽  
Disease State ◽  
Rrna Gene ◽  
Health State ◽  
Rapid Diagnostics ◽  
The 16S Rrna Gene

Variations in the gut microbiome have been associated with changes in health state such as Crohn’s disease. Most surveys characterize the microbiome through analysis of the 16S rRNA gene. An alternative technology that can be used is flow cytometry. In this report we analyzed a disease cohort that has been characterized by both technologies. Changes in microbial community structure are reflected in both types of data. We demonstrate that cytometric fingerprints can be used as a diagnostic tool in order to classify samples according to Crohn’s disease state. These results highlight the potential of flow cytometry to perform rapid diagnostics of microbiome-associated diseases.

scholarly journals Host reproductive cycle influences the pouch microbiota of wild southern hairy-nosed wombats (Lasiorhinus latifrons)

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Sesilje Weiss ◽  
David Taggart ◽  
Ian Smith ◽  
Kristofer M. Helgen ◽  
Raphael Eisenhofer
Keyword(s):  
Microbial Community ◽  
Reproductive Cycle ◽  
Tammar Wallaby ◽  
The Body ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Birth Canal ◽  
Gram Positive Bacteria ◽  
Rigorous Framework ◽  
The 16S Rrna Gene

Abstract Background Marsupials are born much earlier than placental mammals, with most crawling from the birth canal to the protective marsupium (pouch) to further their development. However, little is known about the microbiology of the pouch and how it changes throughout a marsupial’s reproductive cycle. Here, using stringent controls, we characterized the microbial composition of multiple body sites from 26 wild Southern Hairy-nosed Wombats (SHNWs), including pouch samples from animals at different reproductive stages. Results Using qPCR of the 16S rRNA gene we detected a microbial community in the SHNW pouch. We observed significant differences in microbial composition and diversity between the body sites tested, as well as between pouch samples from different reproductive stages. The pouches of reproductively active females had drastically lower microbial diversity (mean ASV richness 19 ± 8) compared to reproductively inactive females (mean ASV richness 941 ± 393) and were dominated by gram positive bacteria from the Actinobacteriota phylum (81.7–90.6%), with the dominant families classified as Brevibacteriaceae, Corynebacteriaceae, Microbacteriaceae, and Dietziaceae. Three of the five most abundant sequences identified in reproductively active pouches had closest matches to microbes previously isolated from tammar wallaby pouches. Conclusions This study represents the first contamination-controlled investigation into the marsupial pouch microbiota, and sets a rigorous framework for future pouch microbiota studies. Our results indicate that SHNW pouches contain communities of microorganisms that are substantially altered by the host reproductive cycle. We recommend further investigation into the roles that pouch microorganisms may play in marsupial reproductive health and joey survival.

scholarly journals Cystic Fibrosis Sputum Impairs the Ability of Neutrophils to Kill Staphylococcus aureus

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 703
Author(s):  
Kayla Fantone ◽  
Samantha L. Tucker ◽  
Arthur Miller ◽  
Ruchi Yadav ◽  
Eryn E. Bernardy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Healthy Volunteers ◽  
Airway Disease ◽  
Neutrophil Extracellular Trap ◽  
Lung Function Decline ◽  
Bacterial Killing ◽  
Cystic Fibrosis Sputum ◽  
Microbial Infections

Cystic fibrosis (CF) airway disease is characterized by chronic microbial infections and infiltration of inflammatory polymorphonuclear (PMN) granulocytes. Staphylococcus aureus (S. aureus) is a major lung pathogen in CF that persists despite the presence of PMNs and has been associated with CF lung function decline. While PMNs represent the main mechanism of the immune system to kill S. aureus, it remains largely unknown why PMNs fail to eliminate S. aureus in CF. The goal of this study was to observe how the CF airway environment affects S. aureus killing by PMNs. PMNs were isolated from the blood of healthy volunteers and CF patients. Clinical isolates of S. aureus were obtained from the airways of CF patients. The results show that PMNs from healthy volunteers were able to kill all CF isolates and laboratory strains of S. aureus tested in vitro. The extent of killing varied among strains. When PMNs were pretreated with supernatants of CF sputum, S. aureus killing was significantly inhibited suggesting that the CF airway environment compromises PMN antibacterial functions. CF blood PMNs were capable of killing S. aureus. Although bacterial killing was inhibited with CF sputum, PMN binding and phagocytosis of S. aureus was not diminished. The S. aureus-induced respiratory burst and neutrophil extracellular trap release from PMNs also remained uninhibited by CF sputum. In summary, our data demonstrate that the CF airway environment limits killing of S. aureus by PMNs and provides a new in vitro experimental model to study this phenomenon and its mechanism.

scholarly journals Correction: Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160726 ◽  
Author(s):  
Giovanni Bacci ◽  
Patrizia Paganin ◽  
Loredana Lopez ◽  
Chiara Vanni ◽  
Claudia Dalmastri ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Cystic Fibrosis Lung ◽  
Lung Function Decline ◽  
Lung Microbiome ◽  
Severe Lung

Increased rate of lung function decline in Australian adolescents with cystic fibrosis

2013 ◽  
Vol 49 (9) ◽  
pp. 873-877 ◽  
Author(s):  
Liam Welsh ◽  
Colin F. Robertson ◽  
Sarath C. Ranganathan
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Lung Function Decline

scholarly journals 260 Predictors of lung function decline in cystic fibrosis

2016 ◽  
Vol 15 ◽  
pp. S117-S118
Author(s):  
F. Ferro ◽  
F. Freitas ◽  
C. Lopes ◽  
R. Costa ◽  
A. Pinto ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Lung Function Decline

scholarly journals Refinement of metabolite detection in cystic fibrosis sputum reveals heme negatively correlates with lung function

2018 ◽  
Author(s):  
Nathaniel R. Glasser ◽  
Ryan C. Hunter ◽  
Theodore G. Liou ◽  
Dianne K. Newman ◽  
Keyword(s):  
Mass Spectrometry ◽  
Cystic Fibrosis ◽  
Lung Function ◽  
High Performance ◽  
16S Rrna Gene Sequencing ◽  
Initial Study ◽  
Rrna Gene ◽  
Sequencing Data ◽  
Unknown Compound ◽  
Mountain West

SummaryPseudomonas aeruginosalung infections are a leading cause of morbidity and mortality in cystic fibrosis (CF) patients (1, 2). Our laboratory has studied a class of small molecules produced byP. aeruginosaknown as phenazines, including pyocyanin and its biogenic precursor phenazine-1-carboxylic acid (PCA). As phenazines are known virulence factors (3), we and others have explored the possibility of using phenazine concentrations as a marker for disease progression (4–6). Previously, we reported that sputum concentrations of pyocyanin and PCA negatively correlate with lung function in cystic fibrosis patients (6). Our study used high performance liquid chromatography (HPLC) to quantify phenazines by UV–vis absorbance after extraction from lung sputum. Since our initial study, methods for metabolite analysis have advanced considerably, aided in large part by usage of mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS). Because a more recent study employing LC-MS/MS revealed a surprising decoupling ofP. aeruginosametabolites in sputum and the detection ofP. aeruginosathrough culturing or microbiome profiles (4), we decided to check whether we could reproduce our previous findings by analyzing sputum samples from a different patient cohort with a new LC-MS instrument in our laboratory. Our new samples were provided by the Mountain West CF Consortium Sputum Biomarker study (7). In the course of performing our new analyses, comparison of our old HPLC data to our new LC-MS data led us to realize that the peak previously assigned to PCA instead originates from heme, and the peak assigned to pyocyanin originates from an as-yet unknown compound. This correction only affects the measurements of phenazines in sputum, and we are confident in the phenazine measurements from isolated cultures and the 16S rRNA gene sequencing data from that study (6). Here we outline the basis for our correction and present additional data showing that heme concentration negatively correlates with lung function in cystic fibrosis patients.

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