Cystic fibrosis airway microbiota associated with outcomes of nontuberculous mycobacterial infection.
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ABSTRACT: Rationale
Pulmonary infections with nontuberculous mycobacteria (NTM) are increasingly prevalent in people with cystic fibrosis (CF). Clinical outcomes following NTM acquisition are highly variable, ranging from transient self-resolving infection to NTM pulmonary disease associated with significant morbidity. Relationships between airway microbiota and variability of NTM outcomes in CF are unclear.Objective
To identify features of CF airway microbiota associated with outcomes of NTM infection.Methods
188 sputum samples, obtained from 24 subjects with CF, each with three or more samples collected from 3.5 years prior to, and up to 6 months following incident NTM infection, were selected from a sample repository. Sputum DNA underwent bacterial 16S rRNA gene sequencing. Airway microbiota were compared based on the primary outcome, a diagnosis of NTM pulmonary disease, using Wilcoxon rank-sum testing, autoregressive integrated moving average modelling and network analyses.Measurements and main results
Subjects with and without NTM pulmonary disease were similar in clinical characteristics, including age and lung function at the time of incident NTM infection. Time-series analyses of sputum samples prior to incident NTM infection identified positive correlations between Pseudomonas, Streptococcus, Veillonella, Prevotella and Rothia with diagnosis of NTM pulmonary disease and with persistent NTM infection. Network analyses identified differences in clustering of taxa between subjects with and without NTM pulmonary disease, and between subjects with persistent versus transient NTM infection.Conclusions
CF airway microbiota prior to incident NTM infection are associated with subsequent outcomes, including diagnosis of NTM pulmonary disease, and persistence of NTM infection. Associations between airway microbiota and NTM outcomes represent targets for validation as predictive markers and for future therapies.
SUBMITTER: Caverly LJ
PROVIDER: S-EPMC8053818 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nontuberculous mycobacteria (NTM) are opportunistic pathogens that affect a relatively small but significant portion of the people with cystic fibrosis (CF), and may cause increased morbidity and mortality in this population. Cultures from the airway are the only test currently in clinical use for detecting NTM. Culture techniques used in clinical laboratories are insensitive and poorly suited for population screening or to follow progression of disease or treatment response. The lack of sensitive and quantitative markers of NTM in the airway impedes patient care and clinical trial design, and has limited our understanding of patterns of acquisition, latency and pathogenesis of disease. Culture-independent markers of NTM infection have the potential to overcome many of the limitations of standard NTM cultures, especially the very slow growth, inability to quantitate bacterial burden, and low sensitivity due to required decontamination procedures. A range of markers have been identified in sputum, saliva, breath, blood, urine, as well as radiographic studies. Proposed markers to detect presence of NTM or transition to NTM disease include bacterial cell wall products and DNA, as well as markers of host immune response such as immunoglobulins and the gene expression of circulating leukocytes. In all cases the sensitivity of culture-independent markers is greater than standard cultures; however, most do not discriminate between various NTM species. Thus, each marker may be best suited for a specific clinical application, or combined with other markers and traditional cultures to improve diagnosis and monitoring of treatment response.
| S-EPMC10965158 | biostudies-literature
Project description:RationaleNontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that may cause chronic lung disease and are one of the most difficult-to-treat infections among persons with cystic fibrosis (pwCF). Environmental factors likely contribute to increased NTM densities, with higher potential for exposure and infection.ObjectiveTo identify water-quality constituents that influence odds of NTM infection among pwCF in Colorado.MethodsWe conducted a population-based nested case-control study using patient data from the Colorado CF Center NTM database. We associated data from pwCF and water-quality data extracted from the Water Quality Portal to estimate odds of NTM infection. Using Bayesian generalized linear models with binomial-distributed discrete responses, we modeled three separate outcomes; any NTM infection, infections due to Mycobacterium avium complex species, and infections due to M. abscessus group species.ResultsWe observed a consistent association with molybdenum in the source water and M. abscessus group species infection among pwCF in all models. For every 1-unit increase in the log concentration of molybdenum in surface water, the odds of infection for those with M. abscessus group species compared to those who were NTM culture-negative increased by 79%. The odds of M. abscessus group infection varied by county; the counties with the highest probability of infection are located along the major rivers.ConclusionsWe have identified molybdenum in the source water as the most predictive factor of M. abscessus group infection among pwCF in Colorado. This finding will help inform patients at risk for NTM of their relative risks in residing within specific regions.
| S-EPMC8920885 | biostudies-literature
Project description:BackgroundPulmonary exacerbations (PEx), frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF). Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.ObjectiveTo determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.MethodsExpectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d.) and late treatment (>7d.) for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE); and circulating C-reactive protein (CRP) were measured.ResultsThirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA) of Pseudomonas (r = -0.67, p<0.001), decreased FEV(1%) predicted (r = 0.49, p = 0.03) and increased CRP (r = -0.58, p = 0.01). In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.ConclusionsAnaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.
| S-EPMC3639911 | biostudies-literature
Project description:Background: Patients with cystic fibrosis (CF) have an elevated lifetime risk of infection and disease caused by nontuberculous mycobacteria (NTM). Currently, there is no method to predict whether patients with cystic fibrosis will develop disease related to non-tuberculous mycobacteria. In non cystic fibrosis populations, several genetic susceptibility factors have been described. In this study, we examined whether patients with cystic fibrosis demonstrate a similar pattern of genetic susceptibility and explored host immune-related biomarkers predictive of NTM pulmonary disease (NTM-PD). Methods: We evaluated whole blood gene expression using bulk RNA-seq in a cohort of CF patients at the time of first isolation of NTM. Differential gene expression was compared in patients who did (n = 12) vs. did not (n= 30) develop NTM-PD following first NTM growth. Results: No differences in demographics or composition of white blood cell sample populations at the time of sample collection were identified between groups. There were no significant differences in the expression of genes previously reported to confer susceptibility to NTM-PD in non-CF populations. However, CF patients who went on to develop NTM-PD had higher expression of genes involved in the interferon ( and ), tumor necrosis factor, and IL6 STAT3 JAK pathways. Conclusion: Patients with CF who develop NTM-PD have increased expression of genes involved in innate immunity, in contrast to non-CF populations where these responses seem to be suppressed.
2022-12-14 | GSE205161 | GEO
Project description:BackgroundNontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review.ObjectivesThe objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 02 September 2016.We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 03 November 2016.Selection criteriaAny randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Data were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.Main resultsOne completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.Authors' conclusionsThis review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.
| S-EPMC6464024 | biostudies-literature
Project description:BackgroundNontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review.ObjectivesThe objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 24 February 2020. We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 21 March 2019.Selection criteriaAny randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Data were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.Main resultsOne completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.Authors' conclusionsThis review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.
| S-EPMC7389742 | biostudies-literature
Project description:Our objectives were to characterise the microbiota in cystic fibrosis (CF) bronchoalveolar lavage fluid (BALF), and determine its relationship to inflammation and disease status.BALF from paediatric and adult CF patients and paediatric disease controls undergoing clinically indicated bronchoscopy was analysed for total bacterial load and for microbiota by 16S rDNA sequencing.We examined 191 BALF samples (146 CF and 45 disease controls) from 13 CF centres. In CF patients aged <2?years, nontraditional taxa (e.gStreptococcus, Prevotella and Veillonella) constituted ?50% of the microbiota, whereas in CF patients aged ?6?years, traditional CF taxa (e.gPseudomonas, Staphylococcus and Stenotrophomonas) predominated. Sequencing detected a dominant taxon not traditionally associated with CF (e.gStreptococcus or Prevotella) in 20% of CF BALF and identified bacteria in 24% of culture-negative BALF. Microbial diversity and relative abundance of Streptococcus, Prevotella and Veillonella were inversely associated with airway inflammation. Microbiota communities were distinct in CF compared with disease controls, but did not differ based on pulmonary exacerbation status in CF.The CF microbiota detected in BALF differs with age. In CF patients aged <2?years, Streptococcus predominates, whereas classic CF pathogens predominate in most older children and adults.
| S-EPMC5935257 | biostudies-literature
Project description:The airways of people with cystic fibrosis (CF) often harbor a diverse microbiota and in recent years, much effort has been invested in cataloguing these. In spite of providing a wealth of insight, this cataloguing tells us little about how the organisms interact with one another in the CF airways. However, such relationships can be inferred using the theoretical framework of the Lotka-Volterra (LV) model. In the current work, we use a generalized Lotka-Volterra model to interrogate the nationwide data collected and curated by the UK CF Registry. This longitudinal dataset (covering the period 2008-2020) contains annual depositions that record the presence/absence of microbial taxa in each patient, their medication, and their CF genotype. Specifically, we wanted to identify trends in ecological relationships between the CF microbiota at a nationwide level, and whether these are potentially affected by medication. Our results show that some medications have a distinct influence on the microbial interactome, especially those that potentially influence the "gut-lung axis" or mucus viscosity. In particular, we found that patients treated with a combination of antimicrobial agents (targeting the airway microbiota), digestive enzymes (assisting in the assimilation of dietary fats and carbohydrates), and DNase (to reduce mucus viscosity) displayed a distinctly different airway interactome compared with patients treated separately with these medications.
| S-EPMC10265647 | biostudies-literature
Project description:BackgroundInfection with nontuberculous mycobacteria (NTM) is of growing clinical concern in people with cystic fibrosis (CF). The epidemiology of infection in children and young people remains poorly understood. Our goal was to investigate the epidemiology of NTM infection in the pediatric age group using data from the UK CF Registry.MethodsData from 2010-2015 for individuals aged <16 years (23200 observations from 5333 unique individuals) were obtained. Univariate analysis of unique individuals comparing all key clinical factors and health outcomes to NTM status was performed. The significant factors that were identified were used to generate a multivariate logistic regression model that, following step-wise removal, generated a final parsimonious model.ResultsThe prevalence of individuals with a NTM-positive respiratory culture increased every year from 2010 (45 [1.3%]) to 2015 (156 [3.8%]). Allergic bronchopulmonary aspergillosis (odds ratio [OR], 2.66; P = 5.0 × 10-8), age (OR, 1.08; P = 3.4 × 10-10), and intermittent Pseudomonas aeruginosa infection (OR, 1.51; P = .004) were significantly associated with NTM infection.ConclusionsNTM infection is of increasing prevalence in the UK pediatric CF population. This study highlights the urgent need for work to establish effective treatment and prevention strategies for NTM infection in young people with CF.
| S-EPMC6376093 | biostudies-literature
Project description:RATIONALE:Pulmonary nontuberculous mycobacteria (NTM) disease represents a significant threat to patients with cystic fibrosis (CF), with an estimated annual prevalence of 12%. Prior studies reported an increasing annual NTM prevalence in the general population, though similar trends in persons with CF have not been assessed. OBJECTIVES:In this study we aimed to identify the prevalence, geographic patterns, temporal trends, and risk factors for NTM positivity by mycobacterial species among persons with CF throughout the United States. METHODS:Using annualized CF Patient Registry (CFFPR) data from 2010 to 2014, we identified patients with mycobacterial culture results to estimate the annual and period prevalence of pathogenic NTM species by demographic and geographic factors. Regression models were used to estimate the annual percent change over time and risk factors for NTM isolation. Geographic patterns were described and mapped. RESULTS:Of 16,153 included persons with CF, 3,211 (20%) had a pathogenic NTM species isolated at least once over the 5-year period; 1,949 (61%) had Mycobacterium avium complex (MAC), and 1,249 (39%) had M. abscessus. The period prevalence was 12% for MAC (confidence interval [CI], 12-13%), 8% for M. abscessus (CI, 7-8%), and 4% for other NTM species (CI, 3.8-4.3%). The period prevalence for MAC was nearly three times greater among patients ≥60 years old with a body mass index < 19 (33% [CI, 16-51%]); this trend was not present for patients with M. abscessus (4% [CI, 0-11%]). NTM prevalence showed a significant relative increase of 5% per year, from 11.0% in 2010 to 13.4% in 2014 (P = 0.0008), although this varied by geographic area. For M. abscessus, the states with the highest prevalence were Hawaii (50%), Florida (17%), and Louisiana (16%), and for MAC they were Nevada (24%), Kansas (21%), and Hawaii and Arizona (both 20%). Study participants with either MAC or M. abscessus were significantly more likely to have been diagnosed with CF at an older age (P < 0.0001), have a lower body mass index (P < 0.0001), higher forced expiratory volume in 1 second % predicted (P < 0.01), and fewer years on chronic macrolide therapy (P < 0.0001). CONCLUSIONS:NTM remains highly prevalent among adults and children with CF in the United States, with one in five affected, and appears to be increasing over time. Prevalence varies by geographic region and by patient-level factors, including older age and receiving an initial CF diagnosis later in life. Routine screening for NTM, including mycobacterial speciation, especially in high-risk geographic areas, is critical to increase our understanding of its epidemiology and changes in prevalence over time.
| S-EPMC6137684 | biostudies-other