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Cough is one of the most common symptoms observed in patients presenting with COVID-19, persisting for an extended duration following SARS-CoV-2 infection. We aim to describe the distribution of airway microbiota and explore its role in patients with post-COVID-19 chronic cough. A total of 57 patients experiencing persistent cough after infection were recruited during the Omicron wave of SARS-CoV-2 in China. Airway microbiota profiling is assessed in nasopharyngeal swab, nasal lavage, and induced sputum samples at 4 and 8 weeks after SARS-CoV-2 infection. Our findings reveal that bacterial families Staphylococcaceae, Corynebacteriaceae, and Enterobacteriaceae are the most prevalent in the upper airway, while Streptococcaceae, Lachnospiraceae, and Prevotellaceae emerge as the most prevalent bacterial families in the lower airway. An increase in the abundance of Staphylococcus in nasopharyngeal swab samples and of Streptococcus in induced sputum samples is observed after one month. Furthermore, the abundance of Staphylococcus identified in nasopharyngeal swab samples at the baseline period emerges as an insightful predictor for improvement in cough severity. In conclusion, dynamic alterations in the airway microbial composition may contribute to the post-COVID-19 chronic cough progression, while the compositional signatures of nasopharyngeal microbiota could reflect the improvement of this disease.
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INTRODUCTION: Recent discoveries in the field of lung microbiota have enabled the investigation of new therapeutic interventions involving the use of inhaled probiotics. AREAS COVERED: This review provides an overview of what is known about the correlation between airway dysbiosis and the development of local and systemic diseases, and how this knowledge can be exploited for therapeutic interventions. In particular, the review focused on attempts to formulate probiotics that can be deposited directly on the airways. EXPERT OPINION: Despite considerable progress since the emergence of respiratory microbiota restoration as a new research field, numerous clinical implications and benefits remain to be determined. In the case of local diseases, once the pathophysiology is understood, manipulating the lung microbiota through probiotic administration is an approach that can be exploited. In contrast, the effect of pulmonary dysbiosis on systemic diseases remains to be clarified; however, this approach could represent a turning point in their treatment.
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Disbiosis , Microbiota , Probióticos , Probióticos/administración & dosificación , Probióticos/uso terapéutico , Humanos , Animales , Administración por Inhalación , Sistema Respiratorio/microbiología , Sistemas de Liberación de Medicamentos , Pulmón/microbiología , Pulmón/metabolismo , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/tratamiento farmacológicoRESUMEN
Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes.
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BACKGROUND: Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban children from ages from 0 to 7 years have previously been described. OBJECTIVE: Our aim was to determine whether distinct respiratory phenotypes are associated with early-life upper respiratory microbiota development and environmental microbial exposures. METHODS: Microbiota profiling was performed using 16S ribosomal RNA-based sequencing of nasal samples collected at age 12 months (n = 120) or age 36 months (n = 142) and paired house dust samples collected at 3 months (12-month, n = 73; 36-month, n = 90) from all 4 centers in the Urban Environment and Childhood Asthma (URECA) cohort. RESULTS: In these high-risk urban children, nasal microbiota increased in diversity between ages 12 and 36 months (ß = 2.04; P = .006). Age-related changes in microbiota evenness differed significantly by respiratory phenotypes (interaction P = .0007), increasing most in the transient wheeze group. At age 12 months, respiratory illness (R2 = 0.055; P = .0001) and dominant bacterial genus (R2 = 0.59; P = .0001) explained variance in nasal microbiota composition, and enrichment of Moraxella and Haemophilus members was associated with both transient and high-wheeze respiratory phenotypes. By age 36 months, nasal microbiota was significantly associated with respiratory phenotypes (R2 = 0.019; P = .0376), and Moraxella-dominated microbiota was associated specifically with atopy-associated phenotypes. Analysis of paired house dust and nasal samples indicated that 12 month olds with low wheeze and atopy incidence exhibited the largest number of shared bacterial taxa with their environment. CONCLUSION: Nasal microbiota development over the course of early childhood and composition at age 3 years are associated with longitudinal respiratory phenotypes. These data provide evidence supporting an early-life window of airway microbiota development that is influenced by environmental microbial exposures in infancy and associates with wheeze- and atopy-associated respiratory phenotypes through age 7 years.
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Microbiota , Fenotipo , Ruidos Respiratorios , Población Urbana , Humanos , Lactante , Preescolar , Masculino , Femenino , Estudios Longitudinales , Asma/microbiología , Asma/epidemiología , Polvo/análisis , Polvo/inmunología , Exposición a Riesgos Ambientales , Nariz/microbiología , ARN Ribosómico 16S/genética , NiñoRESUMEN
IMPORTANCE: PCD is a rare disease characterized by productive cough, rhinitis, and recurrent infections of the upper and lower airways. Because the diagnosis of PCD is often delayed, patients receive more antibiotics, experience a heavier financial burden, and have a worse prognosis; thus, it is very important to identify the pathogeny and use the correct antibiotic. In this large single-center study of PCD microbiota, we identified an outline of the bacterial microbes from the respiratory tract; furthermore, we found that the microbiota diversity in pediatric sputum was richer than that in pediatric BALF through sequencing, indicating a heterogeneous community structure. The microbiota diversity and richness were lower during pulmonary exacerbation than during pulmonary stabilization. A significantly higher abundance of Pseudomonas had a moderate distinguishing effect for lung exacerbation, which attracted more attention for the study of Pseudomonas therapy in pediatric patients with PCD.
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Síndrome de Kartagener , Microbiota , Humanos , Niño , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/tratamiento farmacológico , Pulmón , Esputo/microbiología , Antibacterianos/uso terapéuticoRESUMEN
Inappropriate antibiotic prescriptions are common for patients with upper respiratory tract infections (URTIs). Few data exist regarding the effects of antibiotic administration on airway microbiota among healthy adults. We conducted a randomized, double-blind, placebo-controlled trial to characterize the airway microbiota longitudinally in healthy adults using 16S rRNA gene sequencing and quantification. Both the induced sputum and oral wash samples were collected over a 60-day period following a 3-day intervention with 500 mg azithromycin or placebo. Environmental information, including air quality data (particulate matter [PM2.5] and PM10, air quality index [AQI] values), were also collected during the study. A total of 48 healthy volunteers were enrolled and randomly assigned into two groups. Azithromycin did not alter bacterial load but significantly reduced species richness and Shannon index. Azithromycin exposure resulted in a decrease in the detection rate and relative abundance of different genera belonging to Veillonellaceae, Leptotrichia, Fusobacterium, Neisseria, and Haemophilus. In contrast, the relative abundance of taxa belonging to Streptococcus increased immediately after azithromycin intervention. The shifts in the diversity of the microbiology composition took between 14 and 60 days to recover, depending on the measure used: either UniFrac phylogenetic distance or α-diversity. Outdoor environmental perturbations, especially the high concentration of PM2.5, contributed to novel variability in microbial community composition of the azithromycin group at D30 (30 days after baseline). The network analysis found that azithromycin altered the microbial interactions within airway microbiota. The influence was still obvious at D14 when the relative abundance of most taxa had returned to the baseline level. Compared to the sputum microbiota, oral cavity microbiota had a different pattern of change over time. The induced sputum microbial data can represent the airway microbiota composition in healthy adults. Azithromycin may have transient effects in the airway microbiota of healthy adults and decrease the airway microbiota resilience against outdoor environmental stress. The influence of azithromycin on microbial interactions is noteworthy, although the airway microbiota has returned to a near-baseline level. IMPORTANCE The influence of antibiotic administration on the airway microbiota of healthy adults remains unknown. This study is a randomized, double-blind, placebo-controlled trial aiming to investigate the microbial shifts in airways after exposure to azithromycin among heathy adults. We find that azithromycin changes the airway microbial community composition of healthy adults and decreases the airway microbiota resilience against outdoor environmental stress. This study depicts the longitudinal recovery trajectory of airway microbiota after the antibiotic perturbation and may provide reference for appropriate antibiotic prescription.
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Azitromicina , Microbiota , Humanos , Adulto , Azitromicina/farmacología , Azitromicina/uso terapéutico , Filogenia , ARN Ribosómico 16S/genética , Antibacterianos/uso terapéutico , Material Particulado/farmacologíaRESUMEN
The respiratory tract is home to a diverse microbial community whose influence on local and systemic immune responses is only beginning to be appreciated. Increasing reports have linked changes in this microbiome to a range of pulmonary and extrapulmonary disorders, including asthma, chronic obstructive pulmonary disease and rheumatoid arthritis. Central to many of these findings is the role of IL-17-type immunity as an important driver of inflammation. Despite the crucial role played by IL-17-mediated immune responses in protection against infection, overt Th17 cell responses have been implicated in the pathogenesis of several chronic inflammatory diseases. However, our knowledge of the influence of bacteria that commonly colonise the respiratory tract on IL-17-driven inflammatory responses remains sparse. In this article, we review the current knowledge on the role of specific members of the airway microbiota in the modulation of IL-17-type immunity and discuss how this line of research may support the testing of susceptible individuals and targeting of inflammation at its earliest stages in the hope of preventing the development of chronic disease.
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Inflamación , Interleucina-17 , Pulmón , Microbiota , Humanos , Enfermedad Crónica , Inflamación/inmunología , Interleucina-17/inmunología , Pulmón/inmunología , Pulmón/microbiología , Microbiota/inmunología , Sistema Respiratorio/inmunología , Sistema Respiratorio/microbiologíaRESUMEN
Pulmonary arterial hypertension (PAH) is a severe clinical condition that is characterized pathologically by perivascular inflammation and pulmonary vascular remodeling that ultimately leads to right heart failure. However, current treatments focus on controlling vasoconstriction and have little effect on pulmonary vascular remodeling. Better therapies of PAH require a better understanding of its pathogenesis. With advances in sequencing technology, researchers have begun to focus on the role of the human microbiota in disease. Recent studies have shown that the gut and airway microbiota and their metabolites play an important role in the pathogenesis of PAH. In this review, we summarize the current literature on the relationship between the gut and airway microbiota and PAH. We further discuss the key crosstalk between the gut microbiota and the lung associated with PAH, and the potential link between the gut and airway microbiota in the pathogenesis of PAH. In addition, we discuss the potential of using the microbiota as a new target for PAH therapy.
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Infection and rejection are the two most common complications after lung transplantation (LT) and are associated with increased morbidity and mortality. We aimed to examine the association between the airway microbiota and infection and rejection in lung transplant recipients (LTRs). Here, we collected 181 sputum samples (event-free, n = 47; infection, n = 103; rejection, n = 31) from 59 LTRs, and performed 16S rRNA gene sequencing to analyze the airway microbiota. A significantly different airway microbiota was observed among event-free, infection and rejection recipients, including microbial diversity and community composition. Nineteen differential taxa were identified by linear discriminant analysis (LDA) effect size (LEfSe), with 6 bacterial genera, Actinomyces, Rothia, Abiotrophia, Neisseria, Prevotella, and Leptotrichia enriched in LTRs with rejection. Random forest analyses indicated that the combination of the 6 genera and procalcitonin (PCT) and T-lymphocyte levels showed area under the curve (AUC) values of 0.898, 0.919 and 0.895 to differentiate between event-free and infection recipients, event-free and rejection recipients, and infection and rejection recipients, respectively. In conclusion, our study compared the airway microbiota between LTRs with infection and acute rejection. The airway microbiota, especially combined with PCT and T-lymphocyte levels, showed satisfactory predictive efficiency in discriminating among clinically stable recipients and those with infection and acute rejection, suggesting that the airway microbiota can be a potential indicator to differentiate between infection and acute rejection after LT. IMPORTANCE Survival after LT is limited compared with other solid organ transplantations mainly due to infection- and rejection-related complications. Differentiating infection from rejection is one of the most important challenges to face after LT. Recently, the airway microbiota has been reported to be associated with either infection or rejection of LTRs. However, fewer studies have investigated the relationship between airway microbiota together with infection and rejection of LTRs. Here, we conducted an airway microbial study of LTRs and analyzed the airway microbiota together with infection, acute rejection, and clinically stable recipients. We found different airway microbiota between infection and acute rejection and identify several genera associated with each outcome and constructed a model that incorporates airway microbiota and clinical parameters to predict outcome. This study highlighted that the airway microbiota was a potential indicator to differentiate between infection and acute rejection after LT.
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Trasplante de Pulmón , Microbiota , Humanos , Pulmón , Trasplante de Pulmón/efectos adversos , ARN Ribosómico 16S/genética , Receptores de TrasplantesRESUMEN
BACKGROUND: Accumulating studies have suggested the airway microbiota in lung cancer patients is significantly different from that of healthy controls. However, little is known about the relationship between airway microbiota and important clinical parameters of lung cancer. In this study, we aimed to explore the association between sputum microbiota and lung cancer stage, lymph node metastasis, intrathoracic metastasis, and epidermal growth factor receptor (EGFR) gene mutation. METHODS: The microbiota of sputum samples from 85 newly-diagnosed NSCLC patients were sequenced via 16S rRNA sequencing of the V3-V4 region. Sequencing reads were filtered using QIIME2 and clustered against UPARSE. RESULTS: Alpha- and ß-diversity was significantly different between patients in stages I to II (early stage, ES) and patients in stages III to IV (advanced stage, AS). Linear discriminant analysis Effect Size (LEfSe) identified that genera Granulicatella and Actinobacillus were significantly enriched in ES, and the genus Actinomyces was significantly enriched in AS. PICRUSt2 identified that the NAD salvage pathway was significantly enriched in AS, which was positively associated with Granulicatella. Patients with intrathoracic metastasis were associated with increased genus Peptostreptococcus and incomplete reductive TCA cycle, which was associated with increased Peptostreptococcus. Genera Parvimonas, Pseudomona and L-valine biosynthesis were positively associated with lymph node metastasis. L-valine biosynthesis was related with increased Pseudomona. Finally, the genus Parvimonas was significantly enriched in adenocarcinoma patients with EGFR mutation. CONCLUSION: The taxonomy structure differed between different lung cancer stages. The tumor stage, intrathoracic metastasis, lymph node metastasis, and EGFR mutation were associated with alteration of specific airway genera and metabolic function of sputum microbiota.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Microbiota , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Genes erbB-1 , Humanos , Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: The SARS-CoV-2 virus is responsible for the COVID-19 pandemic. Researchers have been studying the pathogenesis of the virus with the aim to improve our current diagnosis and management strategies. The microbiota have been proposed to play a key role in the pathogenesis of the disease. PURPOSE: To investigate and report on the current available evidence on any associations between the gut and/or airway microbiota and the pathogenesis of COVID-19. METHODS: Using a predefined protocol in compliance with the PRISMA guidelines, a search was conducted on MEDLINE, Science Direct, DOAJ and Cochrane databases on primary research studies assessing the association between COVID-19 infection and the gut and/or airway microbiota. RESULTS: Twenty-two studies were included in the current review; nineteen studies concluded an association between the gut and/or airway dysbiosis and SARS-CoV-2, while 3 studies failed to observe a significant association between the airway microbiome and SARS-CoV-2 infection. Specifically, most studies reported a decrease in microbial diversity and therefore development of intestinal dysbiosis in COVID-19-positive patients compared to healthy controls as well as a possible association between increased intestinal dysbiosis and disease severity. CONCLUSION: During infection with SARS-CoV-2, there are significant changes in the composition of the gut and airway microbiota. Furthermore, the gut microbiota may have a more important role than the airway microbiota in COVID-19 infection. In the future, studies should be more carefully designed to derive more conclusive evidence on the role of the gut and airway microbiota following infection with SARS-CoV-2 which will lead to the formulation of better management strategies in combating COVID-19.
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COVID-19 , Microbioma Gastrointestinal , Disbiosis , Humanos , Pandemias , SARS-CoV-2RESUMEN
Asthma is a multifactorial inflammatory disorder of the respiratory system characterized by high diversity in clinical manifestations, underlying pathological mechanisms and response to treatment. It is generally established that human microbiota plays an essential role in shaping a healthy immune response, while its perturbation can cause chronic inflammation related to a wide range of diseases, including asthma. Systems biology approaches encompassing microbiome analysis can offer valuable platforms towards a global understanding of asthma complexity and improving patients' classification, status monitoring and therapeutic choices. In the present review, we summarize recent studies exploring the contribution of microbiota dysbiosis to asthma pathogenesis and heterogeneity in the context of asthma phenotypes-endotypes and administered medication. We subsequently focus on emerging efforts to gain deeper insights into microbiota-host interactions driving asthma complexity by integrating microbiome and host multi-omics data. One of the most prominent achievements of these research efforts is the association of refractory neutrophilic asthma with certain microbial signatures, including predominant pathogenic bacterial taxa (such as Proteobacteria phyla, Gammaproteobacteria class, especially species from Haemophilus and Moraxella genera). Overall, despite existing challenges, large-scale multi-omics endeavors may provide promising biomarkers and therapeutic targets for future development of novel microbe-based personalized strategies for diagnosis, prevention and/or treatment of uncontrollable asthma.
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Respiratory infections in domestic animals are a major issue for veterinary and livestock industry. Pathogens in the respiratory tract share their habitat with a myriad of commensal microorganisms. Increasing evidence points towards a respiratory pathobiome concept, integrating the dysbiotic bacterial communities, the host and the environment in a new understanding of respiratory disease etiology. During the infection, the airway microbiota likely regulates and is regulated by pathogens through diverse mechanisms, thereby acting either as a gatekeeper that provides resistance to pathogen colonization or enhancing their prevalence and bacterial co-infectivity, which often results in disease exacerbation. Insight into the complex interplay taking place in the respiratory tract between the pathogens, microbiota, the host and its environment during infection in domestic animals is a research field in its infancy in which most studies are focused on infections from enteric pathogens and gut microbiota. However, its understanding may improve pathogen control and reduce the severity of microbial-related diseases, including those with zoonotic potential.
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Microbioma Gastrointestinal , Microbiota , Animales , Animales Domésticos , Disbiosis , Sistema RespiratorioRESUMEN
Alteration in airway microbiota composition and perturbations in microbe-metabolites interactions have been proposed as markers of many diseases. Liu Shen (LS) capsule, a traditional Chinese medicine, was proved as favorable in treating respiratory diseases. However, the effects of the LS capsule in terms of regulating human microorganisms and metabolite profiles are not well known. This study aimed to define and compare the respiratory microbiota composition and circulating and fecal metabolite profiles before and after LS capsule administration. A total of 30 healthy volunteers were recruited. The pharyngeal swab samples were collected for 16S rRNA gene sequencing. The serum and fecal samples were collected to analyze the non-targeted ultra-performance liquid chromatography-tandem mass spectrometry metabolomics. The airway microbial compositions were profoundly altered after LS capsule administration, as evidenced by increased microbial diversity and altered microbial taxa distribution. The increasing abundance of bacterial Bifidobacteria, and Lactobacillus characterized the after-administration groups, and the increasing of abundance bacterial Proteobacteria, Veillonella, Prevotella, Neisseria, and Actinomyces characterized the before-administration groups. Significant discriminations were observed in both serum and fecal metabolic profiles between the before- and after-administration groups. A total number of 134 and 71 significant HMDB taxonomic metabolites including glycerophospholipids, fatty acyls, and prenol lipids in the serum and fecal samples were identified respectively between the before- and after-administration groups. The integrated analysis showed that some altered airway microbiota phylum, such as Bacteroidetes and Proteobacteria, significantly correlated with metabolites in serum and fecal. Hence, our study reported the alternations in the composition and functions of the airway microbial community and the changes in circulating and fecal metabolite profiles after LS capsule administration in healthy humans, thus providing a novel insight into the mechanisms underlying the role of LS capsule treating and preventing related diseases.
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INTRODUCTION: Non-cystic fibrosis bronchiectasis is a respiratory health condition with many possible aetiologies, some of which are potentially reversible in childhood with early diagnosis and appropriate treatment. It is important to understand factors which contribute to progression or potential resolution of bronchiectasis. It is evident that respiratory exacerbations are a key feature of bronchiectasis disease progression. In this pilot study we document how the microbiota of the upper and lower airways presents during the course of an exacerbation and treatment. METHODS: We recruited children (aged 1-15) undergoing antibiotic treatment for bronchiectasis exacerbations at Starship Children's Hospital and outpatient clinics. Sputum and nasal swabs were taken before and after antibiotic treatment. Sample DNA was extracted, then bacterial 16S rRNA genes amplified and sequenced via Illumina MiSeq. RESULTS: Thirty patients were recruited into this study with 81 samples contributing to the final dataset, including 8 patients with complete sets of upper and lower airway samples at both (before and after antibiotics) timepoints. Changes in alpha-diversity over the course of an exacerbation and treatment were non-significant. However, sample composition did alter over the course of an exacerbation, with most notably a reduction in the relative abundance of amplicon sequence variants assigned to Haemophilus. DISCUSSION: Haemophilus has been associated with more severe symptoms in respiratory infections and a reduction in its relative abundance may represent a positive shift in a patient's microbiota. Current treatments for bronchiectasis may preserve bacterial diversity while altering microbiota composition.
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Bronquiectasia , Microbiota , Adolescente , Antibacterianos/uso terapéutico , Bronquiectasia/complicaciones , Bronquiectasia/diagnóstico , Bronquiectasia/tratamiento farmacológico , Niño , Preescolar , Humanos , Lactante , Proyectos Piloto , ARN Ribosómico 16S/genética , Sistema Respiratorio/microbiología , Esputo/microbiologíaRESUMEN
OBJECTIVES/HYPOTHESIS: Eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP and NECRSwNP) show distinguished clinical pathology, but their underlying mechanism remains unclear. We aimed to investigate the clinical, hematological, and histopathological changes in chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes and its association with microbiota. STUDY DESIGN: A comparative cross-sectional study. METHODS: A comparative study of 46 patients with CRSwNP (34.69 ± 16.39 years old) who underwent endoscopic sinus surgery were recruited and subdivided into ECRSwNP and NECRSwNP groups based on eosinophilic tissue inflammation; 12 healthy controls were also included. A structured histopathological analysis was conducted, and complete blood count was determined in patients. Endoscopic-guided middle meatus swabs and fecal samples were collected from the patients and controls and subsequently subjected to 16S rRNA gene sequencing on Illumina MiSeq. RESULTS: Compared to NECRSwNP, ECRSwNP showed a statistically significant increase in the computed tomography score, endoscopic score, blood eosinophil percentage, tissue eosinophil count, inflammation degree, subepithelial edema, and eosinophil aggregation. Airway microbiota communities differed among the three groups. The abundance of Moraxella and Parvimonas was significantly higher in the ECRSwNP group. Distinct microbiota dysbiosis in CRSwNP endotypes was found to be correlated with different clinical pathologies. Moreover, the gut microbiota in ECRSwNP and NECRSwNP showed dysbiosis, that is, significant decrease in the abundance of Actinobacteria in the former and significant increase in the abundance of Enterobacterales and several genera in NECRSwNP. CONCLUSIONS: Significant clinical pathology and microbiota changes were evident in patients with ECRSwNP and NECRSwNP. Distinct microbiota dysbiosis was correlated with different clinical pathologies. Understanding these differences may improve the prognosis and treatment of chronic rhinosinusitis. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E34-E44, 2021.
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Microbiota , Pólipos Nasales/patología , Rinitis/microbiología , Rinitis/patología , Sinusitis/microbiología , Sinusitis/patología , Adolescente , Adulto , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/complicaciones , Rinitis/complicaciones , Sinusitis/complicaciones , Adulto JovenRESUMEN
BACKGROUND: Early-life exposures to antibiotics may increase the risk of developing childhood asthma. However, little is known about the mechanisms linking antibiotic exposures to asthma. We hypothesized that changes in the nasal airway microbiota serve as a causal mediator in the antibiotics-asthma link. METHODS: In a population-based birth-cohort study in Finland, we identified longitudinal nasal microbiota profiles during age 2-24 months using 16S rRNA gene sequencing and an unsupervised machine learning approach. We performed a causal mediation analysis to estimate the natural direct effect of systemic antibiotic treatments during age 0-11 months on risks of developing physician-diagnosed asthma by age 7 years and the natural indirect (causal mediation) effect through longitudinal changes in nasal microbiota. RESULTS: In our birth cohort of 697 children, 8.0% later developed asthma. Exposure to ≥2 antibiotic treatments during age 0-11 months was associated with a 4.0% increase in the absolute risk of developing asthma (absolute increase, 95% CI, .9-7.2%; Pâ =â .006). The unsupervised clustering approach identified 6 longitudinal nasal microbiota profiles. Infants with a larger number of antibiotic treatments had a higher risk of having a profile with early Moraxella sparsity (per each antibiotic treatment, adjusted RRR, 1.38; 95% CI, 1.15-1.66; Pâ <â .001). This effect of antibiotics on asthma was partly mediated by longitudinal changes in the nasal microbiota (natural indirect effect, Pâ =â .008), accounting for 16% of the total effect. CONCLUSIONS: Early exposures to antibiotics were associated with increased risk of asthma; the effect was mediated, in part, by longitudinal changes in the nasal airway microbiota.
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Asma , Microbiota , Antibacterianos/efectos adversos , Asma/epidemiología , Niño , Preescolar , Estudios de Cohortes , Finlandia/epidemiología , Humanos , Lactante , Recién Nacido , ARN Ribosómico 16SRESUMEN
Homeostatic mucosal immune responses are fine-tuned by naturally evolved interactions with native microbes, and integrating these relationships into experimental models can provide new insights into human diseases. Here, we leverage a murine-adapted airway microbe, Bordetella pseudohinzii (Bph), to investigate how chronic colonization impacts mucosal immunity and the development of allergic airway inflammation (AAI). Colonization with Bph induces the differentiation of interleukin-17A (IL-17A)-secreting T-helper cells that aid in controlling bacterial abundance. Bph colonization protects from AAI and is associated with increased production of secretory leukocyte protease inhibitor (SLPI), an antimicrobial peptide with anti-inflammatory properties. These findings are additionally supported by clinical data showing that higher levels of upper respiratory SLPI correlate both with greater asthma control and the presence of Haemophilus, a bacterial genus associated with AAI. We propose that SLPI could be used as a biomarker of beneficial host-commensal relationships in the airway.
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Interacciones Microbiota-Huesped , Hipersensibilidad/microbiología , Hipersensibilidad/patología , Inflamación/patología , Pulmón/microbiología , Pulmón/patología , Microbiota , Inhibidor Secretorio de Peptidasas Leucocitarias/metabolismo , Células A549 , Adolescente , Adulto , Animales , Antígenos/metabolismo , Bordetella/fisiología , Niño , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Interacciones Microbiota-Huesped/genética , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/inmunología , Inmunidad , Inflamación/complicaciones , Inflamación/inmunología , Inflamación/microbiología , Pulmón/inmunología , Ratones Endogámicos C57BL , Ovalbúmina/inmunología , Células Th17/inmunología , Transcriptoma/genética , Adulto JovenRESUMEN
The application of next-generation sequencing tools revealed that the cystic fibrosis respiratory tract is a polymicrobial environment. We have characterized the airway bacterial microbiota of five adult patients with cystic fibrosis during a 14-month period by 16S rRNA tag sequencing using the Illumina technology. Microbial diversity, estimated by the Shannon index, varied among patient samples collected throughout the follow-up period. The beta diversity analysis revealed that the composition of the airway microbiota was highly specific for each patient, showing little variation among the samples of each patient analyzed over time. The composition of the bacterial microbiota did not reveal any emerging pathogen predictor of pulmonary disease in cystic fibrosis or of its unfavorable clinical progress, except for unveiling the presence of anaerobic microorganisms, even without any established clinical association. Our results could potentialy help us to translate and develop strategies in response to the pathobiology of this disease, particularly because it represents an innovative approach for CF centers in Brazil.
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Fibrosis Quística/microbiología , Microbiota , Sistema Respiratorio/microbiología , Adulto , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Brasil , ADN Bacteriano/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Laryngotracheal stenosis is an obstructive respiratory disease that leads to voicing difficulties and dyspnea with potential life-threatening consequences. The majority of incidences are due to iatrogenic etiology from endotracheal tube intubation; however, airway scarring also has idiopathic causes. While recent evidence suggests a microbial contribution to mucosal inflammation, the microbiota associated with different types of stenosis has not been characterized. High-throughput sequencing of the V4 region of the16S rRNA gene was performed to characterize the microbial communities of 61 swab samples from 17 iatrogenic and 10 adult idiopathic stenosis patients. Nonscar swabs from stenosis patients were internal controls, and eight swabs from four patients without stenosis represented external controls. Significant differences in diversity were observed between scar and nonscar samples and among sample sites, with decreased diversity detected in scar samples and the glottis region. Permutational analysis of variance (PERMANOVA) results revealed significant differences in community composition for scar versus nonscar samples, etiology type, sample site, groups (iatrogenic, idiopathic, and internal and external controls), and individual patients. Pairwise Spearman's correlation revealed a strong inverse correlation between Prevotella and Streptococcus among all samples. Finally, bacteria in the family Moraxellaceae were found to be distinctly associated with idiopathic stenosis samples in comparison with external controls. Our findings suggest that specific microbiota and community shifts are present with laryngotracheal stenosis in adults, with members of the family Moraxellaceae, including the known pathogens Moraxella and Acinetobacter, identified in idiopathic scar. Further work is warranted to elucidate the contributing role of bacteria on the pathogenesis of laryngotracheal stenosis.IMPORTANCE The laryngotracheal region resides at the intersection between the heavily studied nasal cavity and lungs; however, examination of the microbiome in chronic inflammatory conditions of the subglottis and trachea remains scarce. To date, studies have focused on the microbiota of the vocal folds, or the glottis, for laryngeal carcinoma, as well as healthy larynges, benign vocal fold lesions, and larynges exposed to smoking and refluxate. In this study, we seek to examine the structure and composition of the microbial community in adult laryngotracheal stenosis of various etiologies. Due to the heterogeneity among the underlying pathogenesis mechanisms and clinical outcomes seen in laryngotracheal stenosis disease, we hypothesized that different microbial profiles will be detected among various stenosis etiology types. Understanding differences in the microbiota for subglottic stenosis subtypes may shed light upon etiology-specific biomarker identification and offer novel insights into management approaches for this debilitating disease.