scholarly journals Taxonomic variability over functional stability in the microbiome of Cystic Fibrosis patients chronically infected by Pseudomonas aeruginosa

2019 ◽  
Author(s):  
Giovanni Bacci ◽  
Giovanni Taccetti ◽  
Daniela Dolce ◽  
Federica Armanini ◽  
Nicola Segata ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Treatment ◽  
Clinical Status ◽  
Patient Specific ◽  
Metagenomic Sequencing ◽  
Antibiotic Exposure ◽  
Large Core ◽  
Microbial Composition ◽  
Lung Microbiome ◽  
Core Set

AbstractAlthough the cystic fibrosis (CF) lung microbiome has been characterized in several studies, little is still known about the functions harboured by those bacteria, and how they change with disease status and antibiotic treatment. The aim of this study was to investigate the taxonomic and functional temporal dynamics of airways microbiome in a cohort of CF patients. Multiple sputum samples were collected over 15 months from 22 patients with chronic P. aeruginosa infection, for a total of 79 samples. DNA extracted from samples was subjected to shotgun metagenomic sequencing allowing either strain-level taxonomic profiling and assessment of the functional metagenomic repertoire. High inter-patient taxonomic heterogeneity was found with short-term compositional changes during exacerbations and following antibiotic treatment. Each patient exhibited distinct sputum microbial communities at the taxonomic level, and strain-specific colonization of traditional CF pathogens, including P. aeruginosa, and emerging pathogens. Sputum microbiome was found to be extraordinarily resilient following antibiotic treatment, with rapid recovery of taxa and metagenome-associated gene functions. In particular, a large core set of genes, including antibiotic resistance genes, were shared across patients despite observed differences in clinical status or antibiotic treatment, and constantly detected in the lung microbiome of all subjects independently from known antibiotic exposure, suggesting an overall microbiome-associated functions stability despite taxonomic fluctuations of the communities.IMPORTANCEWhile the dynamics of CF sputum microbial composition were highly patient-specific, the overall sputum metagenome composition was stable, showing a high resilience along time and antibiotic exposure. The high degree of redundancy in the CF lung microbiome could testifies ecological aspects connected to the disease that were never considered so far, as the large core-set of genes shared between patients despite observed differences in clinical status or antibiotic treatment. Investigations on the actual functionality (e.g. by metatranscriptomics) of the identified core-set of genes could provide clues on genetic function of the microbiome to be targeted in future therapeutic treatments.

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 Lumacaftor/ivacaftor changes the lung microbiome and metabolome in cystic fibrosis patients

2021 ◽  
pp. 00731-2020
Author(s):  
Anne H. Neerincx ◽  
Katrine Whiteson ◽  
Joann L. Phan ◽  
Paul Brinkman ◽  
Mahmoud I. Abdel-Aziz ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multiple Testing ◽  
Fluid Transport ◽  
Statistical Significance ◽  
Routine Care ◽  
Microbial Composition ◽  
Lung Microbiome ◽  
16S Rna ◽  
Cf Transmembrane Conductance Regulator

RationaleTargeted cystic fibrosis (CF) therapy with lumacaftor/ivacaftor partly restores chloride channel function and improves epithelial fluid transport in the airways. Consequently, changes in the microbiome that is adapted to CF lungs may occur.ObjectivesTo investigate the effects of lumacaftor/ivacaftor on respiratory microbial composition and microbial metabolic activity by repeatedly sampling the lower respiratory tract.MethodsThis was a single-center longitudinal observational cohort study in adult CF patients with a homozygous Phe508del mutation. Lung function measurements and microbial cultures of sputum were performed as part of routine care. An oral and nasal wash, and a breath sample were collected before and every 3 months after starting therapy, up to 1 year.ResultsTwenty patients were included in this study. Amplicon 16S RNA and metagenomics sequencing revealed that Pseudomonas aeruginosa was most abundant in sputum and seemed to decrease after 6 months of treatment, although this did not reach statistical significance after correction for multiple testing. Two types of untargeted metabolomics analyses in sputum showed a change in metabolic composition between 3 and 9 months that almost returned to baseline levels after 12 months of treatment. The volatile metabolic composition of breath was significantly different after 3 months and remained different from baseline until 12 months follow up.ConclusionsAfter starting CF transmembrane conductance regulator (CFTR) modulating treatment in CF patients with a homozygous Phe508del mutation, a temporary and moderate change in lung microbiome is observed, which is mainly characterised by a reduction in the relative abundance of Pseudomonas aeruginosa.

scholarly journals Legionella pneumophila infection and antibiotic treatment engenders a highly disturbed pulmonary microbiome with decreased microbial diversity

2019 ◽  
Author(s):  
Ana Elena Pérez-Cobas ◽  
Christophe Ginevra ◽  
Christophe Rusniok ◽  
Sophie Jarraud ◽  
Carmen Buchrieser
Keyword(s):  
Antibiotic Treatment ◽  
Legionella Pneumophila ◽  
Severe Pneumonia ◽  
Resistant Bacteria ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Bacterial Composition ◽  
Lung Microbiome ◽  
The Impact ◽  
Healthy Lung

ABSTRACTBackgroundLung microbiome analyses have shown that the healthy lung is not sterile but it is colonized like other body sites by bacteria, fungi and viruses. However, little is known about the microbial composition of the lung microbiome during infectious diseases such as pneumonia and how it evolves during antibiotic therapy. To better understand the impact of the composition of the pulmonary microbiome on severity and outcome of pneumonia we analysed the composition and evolution of the human lung microbiome during pneumonia caused by the bacterium Legionella pneumophila.ResultsWe collected 10 bronchoalveolar lavage (BAL) samples from three patients during long-term hospitalisation due to severe pneumonia and performed a longitudinal in-depth study of the composition of their lung microbiome by high-throughput Illumina sequencing of the 16S rRNA gene (bacteria and archaea), ITS region (fungi) and 18S rRNA gene (eukaryotes). We found that the composition of the bacterial lung microbiome during pneumonia is hugely disturbed containing a very high percentage of the pathogen, a very low bacterial diversity, and an increased presence of opportunistic microorganisms such as species belonging to Staphylococcaceae and Streptococcaceae. The microbiome of antibiotic treated patients cured from pneumonia represented a different perturbation state with a higher abundance of resistant bacteria (mainly Firmicutes) and a significantly different bacterial composition as that found in healthy individuals. In contrast, the mycobiome remains more stable during pneumonia and antimicrobial therapy. Interestingly we identified possible cooperation within and between both communities. Furthermore, archaea (Methanobrevibacter) and protozoa (Acanthamoeba and Trichomonas) were detected.ConclusionsBacterial pneumonia leads to a collapse of the healthy microbiome and a strongly disturbed bacterial composition of the pulmonary microbiome that is dominated by the pathogen. Antibiotic treatment allows some bacteria to regrow or recolonize the lungs but the restoration of a healthy lung microbiome composition is only regained a certain time after the antibiotic treatment. Archaea and protozoa should also be considered, as they might be important but yet overseen members of the lung microbiome. Interactions between the micro- and the mycobiome might play a role in the restoration of the microbiome and the clinical evolution of the disease.

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 Untargeted Metagenomic Investigation of the Airway Microbiome of Cystic Fibrosis Patients with Moderate-Severe Lung Disease

2020 ◽  
Vol 8 (7) ◽  
pp. 1003 ◽  
Author(s):  
Giovanni Bacci ◽  
Giovanni Taccetti ◽  
Daniela Dolce ◽  
Federica Armanini ◽  
Nicola Segata ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Temporal Dynamics ◽  
Clinical Status ◽  
Antibiotic Resistance Genes ◽  
Lower Airway ◽  
Metagenomic Sequencing ◽  
Taxonomic Profiling ◽  
Shotgun Metagenomic Sequencing ◽  
Airway Microbiome

Although the cystic fibrosis (CF) lung microbiota has been characterized in several studies, little is still known about the temporal changes occurring at the whole microbiome level using untargeted metagenomic analysis. The aim of this study was to investigate the taxonomic and functional temporal dynamics of the lower airway microbiome in a cohort of CF patients. Multiple sputum samples were collected over 15 months from 22 patients with advanced lung disease regularly attending three Italian CF Centers, given a total of 79 samples. DNA extracted from samples was subjected to shotgun metagenomic sequencing allowing both strain-level taxonomic profiling and assessment of the functional metagenomic repertoire. High inter-patient taxonomic heterogeneity was found with short-term compositional changes across clinical status. Each patient exhibited distinct sputum microbial communities at the taxonomic level, and strain-specific colonization of both traditional and atypical CF pathogens. A large core set of genes, including antibiotic resistance genes, were shared across patients despite observed differences in clinical status, and consistently detected in the lung microbiome of all subjects independently from known antibiotic exposure. In conclusion, an overall stability in the microbiome-associated genes was found despite taxonomic fluctuations of the communities.

scholarly journals Lung microbiome alterations in NSCLC patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leliang Zheng ◽  
Ruizheng Sun ◽  
Yinghong Zhu ◽  
Zheng Li ◽  
Xiaoling She ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Rare Species ◽  
Common Species ◽  
Oral Microbiota ◽  
Metagenomic Sequencing ◽  
Microbial Composition ◽  
Lung Microbiome ◽  
Egfr Expression ◽  
Nsclc Patients

AbstractLung is colonized by a diverse array of microbes and the lung microbiota is profoundly involved in the development of respiratory diseases. There is little knowledge about the role of lung microbiota dysbiosis in lung cancer. In this study, we performed metagenomic sequencing on bronchoalveolar lavage (BAL) from two different sampling methods in non-small cell lung cancer (NSCLC) patients and non-cancer controls. We found the obvious variation between bronchoscopy samples and lobectomy samples. Oral taxa can be found in both bronchoscopy and lobectomy samples and higher abundance of oral taxa can be found in bronchoscopy samples. Although the NSCLC patients had similar microbial communities with non-cancer controls, rare species such as Lactobacillus rossiae, Bacteroides pyogenes, Paenibacillus odorifer, Pseudomonas entomophila, Magnetospirillum gryphiswaldense, fungus Chaetomium globosum et al. showed obvious difference between NSCLC patients and non-cancer controls. Age-, gender-, and smoking-specific species and EGFR expression-related species in NSCLC patients were detected. There results implicated that different lung segments have differential lung microbiome composition. The oral taxa are found in the lobectomy samples suggesting that oral microbiota are the true members of lung microbiota, rather than contamination during bronchoscopy. Lung cancer does not obviously alter the global microbial composition, while rare species are altered more than common species. Certain microbes may be associated with lung cancer progression.

scholarly journals A large-scale metagenomic survey dataset of the post-weaning piglet gut lumen

GigaScience ◽  
2021 ◽  
Vol 10 (6) ◽  
Author(s):  
Daniela Gaio ◽  
Matthew Z DeMaere ◽  
Kay Anantanawat ◽  
Graeme J Eamens ◽  
Michael Liu ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Gut Microbiota ◽  
Antibiotic Treatment ◽  
Large Scale ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Sample Collection ◽  
Microbial Composition ◽  
Intensive Farming ◽  
Wide Range

Abstract Background Early weaning and intensive farming practices predispose piglets to the development of infectious and often lethal diseases, against which antibiotics are used. Besides contributing to the build-up of antimicrobial resistance, antibiotics are known to modulate the gut microbial composition. As an alternative to antibiotic treatment, studies have previously investigated the potential of probiotics for the prevention of postweaning diarrhea. In order to describe the post-weaning gut microbiota, and to study the effects of two probiotics formulations and of intramuscular antibiotic treatment on the gut microbiota, we sampled and processed over 800 faecal time-series samples from 126 piglets and 42 sows. Results Here we report on the largest shotgun metagenomic dataset of the pig gut lumen microbiome to date, consisting of &gt;8 Tbp of shotgun metagenomic sequencing data. The animal trial, the workflow from sample collection to sample processing, and the preparation of libraries for sequencing, are described in detail. We provide a preliminary analysis of the dataset, centered on a taxonomic profiling of the samples, and a 16S-based beta diversity analysis of the mothers and the piglets in the first 5 weeks after weaning. Conclusions This study was conducted to generate a publicly available databank of the faecal metagenome of weaner piglets aged between 3 and 9 weeks old, treated with different probiotic formulations and intramuscular antibiotic treatment. Besides investigating the effects of the probiotic and intramuscular antibiotic treatment, the dataset can be explored to assess a wide range of ecological questions with regards to antimicrobial resistance, host-associated microbial and phage communities, and their dynamics during the aging of the host.

scholarly journals Detection and monitoring of lung inflammation in cystic fibrosis during respiratory tract exacerbation using diffusion-weighted magnetic resonance imaging

2017 ◽  
Vol 50 (1) ◽  
pp. 1601437 ◽  
Author(s):  
Pierluigi Ciet ◽  
Silvia Bertolo ◽  
Mirco Ros ◽  
Eleni Rosalina Andrinopoulou ◽  
Valentina Tavano ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cystic Fibrosis ◽  
Magnetic Resonance ◽  
Lung Function ◽  
Respiratory Tract ◽  
Antibiotic Treatment ◽  
Clinical Status ◽  
Control Group ◽  
Resonance Imaging ◽  
Weighted Magnetic Resonance Imaging

The aim was to investigate whether diffusion-weighted magnetic resonance imaging (DWI) detects and monitors inflammatory and lung function changes during respiratory tract exacerbations (RTE) treatment in patients with cystic fibrosis (CF).29 patients with RTE underwent DWI pre- and post-antibiotic treatment. A control group of 27 stable patients, matched for age and sex, underwent DWI with the same time gap as those undergoing RTE treatment. Clinical status and lung function were assessed at each DWI time point. The CF-MRI scoring system was used to assess structural lung changes in both CF groups.Significant reduction in the DWI score over the course of antibiotic treatment (p<0.0001) was observed in patients with RTE, but not in the control group. DWI score had a strong inverse correlation with clinical status (r=−0.504, p<0.0001) and lung function (r=−0.635, p<0.0001) in patients with RTE. Interestingly, there were persistent significant differences in the CF-MRI score between the RTE and control group at both baseline and follow-up (p<0.001), while the differences in DWI score were only observed at baseline (p<0.001).DWI is a promising imaging method for noninvasive detection of pulmonary inflammation during RTE, and may be used to monitor treatment efficacy of anti-inflammatory treatment.

scholarly journals Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study)

2021 ◽  
Vol 9 (3) ◽  
pp. 647
Author(s):  
Daniel Laubitz ◽  
Katri Typpo ◽  
Monica Midura-Kiela ◽  
Clairessa Brown ◽  
Albert Barberán ◽  
...  
Keyword(s):  
Pilot Study ◽  
Gut Microbiota ◽  
Antibiotic Treatment ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Antibiotic Exposure ◽  
Microbial Composition ◽  
Human Lifespan ◽  
Rrna Gene Sequencing ◽  
Young Mice

Antibiotics have improved survival from previously deadly infectious diseases. Antibiotics alter the microbial composition of the gut microbiota, and these changes are associated with diminished innate immunity and decline in cognitive function in older adults. The composition of the human microbiota changes with age over the human lifespan. In this pilot study, we sought to identify if age is associated with differential recovery of the microbiota after antibiotic exposure. Using 16S rRNA gene sequencing, we compared recovery of the gut microbiota after the 10-day broad-spectrum antibiotic treatment in wild-type C57BL/six young and older mice. Immediately after antibiotic cessation, as expected, the number of ASVs, representing taxonomic richness, in both young and older mice significantly declined from the baseline. Mice were followed up to 6 months after cessation of the single 10-day antibiotic regimen. The Bray-Curtis index recovered within 20 days after antibiotic cessation in young mice, whereas in older mice the microbiota did not fully recover during the 6-months of follow-up. Bifidobacterium, Dubosiella, Lachnospiraceae_NK4A136_group became dominant in older mice, whereas in young mice, the bacteria were more evenly distributed, with only one dominant genus of Anaeroplasma. From 45 genera that became extinct after antibiotic treatment in young mice, 31 (68.9%) did not recover by the end of the study. In older mice, from 36 extinct genera, 27 (75%) did not recover. The majority of the genera that became extinct and never recovered belonged to Firmicutes phylum and Clostridiales family. In our study, age was a factor associated with the long-term recovery of the gut microbiota after the 10-day antibiotic treatment.

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