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UNLABELLED: Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soil Bacillus subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides, while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheeps blood agar inhibited the growth of Coccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth of Coccidioides to controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition of Coccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily included Lactobacillus and Staphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo. IMPORTANCE: Coccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%-80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%-10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.

The lungs, as vital organs in the human body, continuously engage in gas exchange with the external environment. The lung microbiota, a critical component in maintaining internal homeostasis, significantly influences the onset and progression of diseases. Beneficial interactions between the host and its microbial community are essential for preserving the host's health, whereas disease development is often linked to dysbiosis or alterations in the microbial community. Evidence has demonstrated that changes in lung microbiota contribute to the development of major chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung cancer. However, in-depth mechanistic studies are constrained by the small scale of the lung microbiota and its susceptibility to environmental pollutants and other factors, leaving many questions unanswered. This review examines recent research on the lung microbiota and lung diseases, as well as methodological advancements in studying lung microbiota, summarizing the ways in which lung microbiota impacts lung diseases and introducing research methods for investigating lung microbiota. [ABSTRACT FROM AUTHOR]

Objective: This retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis. Methods: A total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study. Baseline demographic and clinical characteristics were compared between survival and non-survival groups. Microbial composition and diversity were analyzed using alpha and beta diversity metrics. Additionally, LEfSe analysis and machine learning methods were employed to identify key pathogenic microorganism associated with short-term mortality. Microbial interaction modes were assessed through network co-occurrence analysis. Results: The overall 28-day mortality rate was 37.7% in severe pneumonia. Nonsurvival patients had a higher prevalence of hypertension and exhibited higher APACHE II and SOFA scores, higher procalcitonin (PCT), and shorter hospitalization duration. Microbial α and β diversity analysis showed no significant differences between the two groups. However, distinct species diversity patterns were observed, with the non-survival group showing a higher abundance of Acinetobacter baumannii, Klebsiella pneumoniae, and Enterococcus faecium, while the survival group had a higher prevalence of Corynebacterium striatum and Enterobacter. LEfSe analysis identified 29 distinct terms, with 10 potential markers in the non-survival group, including Pseudomonas sp. and Enterococcus durans. Machine learning models selected 16 key pathogenic bacteria, such as Klebsiella pneumoniae, significantly contributing to predicting short-term mortality. Network co-occurrence analysis revealed greater complexity in the non-survival group compared to the survival group, with differences in central genera. Conclusion: Our study highlights the potential significance of lung microbiota composition in predicting short-term prognosis in severe pneumonia patients. Differences in microbial diversity and composition, along with distinct microbial interaction modes, may contribute to variations in short-term outcomes. Further research is warranted to elucidate the clinical implications and underlying mechanisms of these findings. [ABSTRACT FROM AUTHOR]

Background: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). Methods: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. Results: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (−), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (−) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. Conclusion: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO. [ABSTRACT FROM AUTHOR]

Abstract Background Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). Methods This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. Results Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (−), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (−) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. Conclusion Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

Jingli Yang,1– 4 Yu He,1– 5 Qing Ai,1– 4 Chan Liu,1– 4 Qiqi Ruan,1– 4 Yuan Shi1– 4 1Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2National Clinical Research Center for Child Health and Disorders, Chongqing, People’s Republic of China; 3Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Neonatology, Jiangxi Hospital Affiliated to Children’s Hospital of Chongqing Medical University, Jiangxi, People’s Republic of ChinaCorrespondence: Yuan Shi, Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China, Email shiyuan@hospital.cqmu.edu.cnPurpose: Neonatal Acute Respiratory Distress Syndrome (NARDS) is a severe respiratory crisis threatening neonatal life. We aim to identify changes in the lung-gut microbiota and lung-plasma tryptophan metabolites in NARDS neonates to provide a differentiated tool and aid in finding potential therapeutic targets.Patients and Methods: Lower respiratory secretions, faeces and plasma were collected from 50 neonates including 25 NARDS patients (10 patients with mild NARDS in the NARDS_M group and 15 patients with moderate-to-severe NARDS in the NARDS_S group) and 25 control patients screened based on gestational age, postnatal age and birth weight. Lower airway secretions and feces underwent 16S rRNA gene sequencing to understand the microbial communities in the lung and gut, while lower airway secretions and plasma underwent LC-MS analysis to understand tryptophan metabolites in the lung and blood. Correlation analyses were performed by comparing differences in microbiota and tryptophan metabolites between NARDS and control, NARDS_S and NARDS_M groups.Results: Significant changes in lung and gut microbiota as well as lung and plasma tryptophan metabolites were observed in NARDS neonates compared to controls. Proteobacteria and Bacteroidota were increased in the lungs of NARDS neonates, whereas Firmicutes, Streptococcus, and Rothia were reduced. Lactobacillus in the lungs decreased in NARDS_S neonates. Indole-3-carboxaldehyde decreased in the lungs of NARDS neonates, whereas levels of 3-hydroxykynurenine, indoleacetic acid, indolelactic acid, 3-indole propionic acid, indoxyl sulfate, kynurenine, and tryptophan decreased in the lungs of the NARDS_S neonates. Altered microbiota was significantly related to tryptophan metabolites, with changes in lung microbiota and tryptophan metabolites having better differentiated ability for NARDS diagnosis and grading compared to gut and plasma.Conclusion: Significant changes occurred in the lung-gut microbiota and lung-plasma tryptophan metabolites of NARDS neonates. Alterations in lung microbiota and tryptophan metabolites were better discriminatory for the diagnosis and grading of NARDS.Keywords: Neonatal acute respiratory distress syndrome, NARDS, lung microbiota, gut microbiota, tryptophan metabolites, correlation analysis, predictive diagnosis

The increasing prevalence of non-tuberculous mycobacterium (NTM) infections alongside tuberculosis (TB) underscores a pressing public health challenge. Yet, the mechanisms governing their infection within the lung remain poorly understood. Here, we integrate metagenomic sequencing, metabolomic sequencing, machine learning classifiers, SparCC, and MetOrigin methods to profile bronchoalveolar lavage fluid (BALF) samples from NTM/TB patients. Our aim is to unravel the intricate interplay between lung microbial communities and NTM/Mycobacterium tuberculosis infections. Our investigation reveals a discernible reduction in the compositional diversity of the lung microbiota and a diminished degree of mutual interaction concomitant with NTM/TB infections. Notably, NTM patients exhibit a distinct microbial community characterized by marked specialization and notable enrichment of Pseudomonas aeruginosa and Staphylococcus aureus, driving pronounced niche specialization for NTM infection. Simultaneously, these microbial shifts significantly disrupt tryptophan metabolism in NTM infection, leading to an elevation of kynurenine. Mycobacterium intracellulare, Mycobacterium paraintracellulare, Mycobacterium abscessus, and Pseudomonas aeruginosa have been implicated in the metabolic pathways associated with the conversion of indole to tryptophan via tryptophan synthase within NTM patients. Additionally, indoleamine-2,3-dioxygenase converts tryptophan into kynurenine, fostering an immunosuppressive milieu during NTM infection. This strategic modulation supports microbial persistence, enabling evasion from immune surveillance and perpetuating a protracted state of NTM infection. The elucidation of these nuanced microbial and metabolic dynamics provides a profound understanding of the intricate processes underlying NTM and TB infections, offering potential avenues for therapeutic intervention and management.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is crucial for protecting vulnerable individuals, yet individuals with type 2 diabetes mellitus (T2DM) often exhibit impaired vaccine responses. Emerging evidence suggests that the composition of the host microbiota, crucial in immune regulation and development, influences vaccine efficacy. This study aimed to characterize the relationships between the SARS-CoV-2 inactivated vaccine and the host microbiota (specifically, gut and lung microbiota) of C57BL/6 mice with T2DM. Employing 16S rRNA metagenomic sequencing and ultra-high-performance liquid chromatography-mass spectrometry, we observed lower alpha diversity and distinct beta diversity in fecal microbiota before vaccination and in gut microbiota 28 days post-vaccination between T2DM mice and healthy mice. Compared with healthy mice, T2DM mice showed a higher Firmicutes/Bacteroidetes ratio 28 days post-vaccination. Significant alterations in gut microbiota composition were detected following vaccination, while lung microbiota remained unchanged. T2DM was associated with a diminished initial IgG antibody response against the spike protein, which subsequently normalized after 28 days. Notably, the initial IgG response positively correlated with fecal microbiota alpha diversity pre-vaccination. Furthermore, after 28 days, increased relative abundance of gut probiotics (Bifidobacterium and Lactobacillus) and higher levels of the gut bacterial tryptophan metabolite, indole acrylic acid, were positively associated with IgG levels. These findings suggest a potential link between vaccine efficacy and gut microbiota composition. Nonetheless, further research is warranted to elucidate the precise mechanisms underlying the impact of the gut microbiome on vaccine response. Overall, this study enhances our understanding of the intricate relationships among host microbiota, SARS-CoV-2 vaccination, and T2DM, with potential implications for improving vaccine efficacy.IMPORTANCEOver 7 million deaths attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by 6 May 2024 underscore the urgent need for effective vaccination strategies. However, individuals with type 2 diabetes mellitus (T2DM) have been identified as particularly vulnerable and display compromised immune responses to vaccines. Concurrently, increasing evidence suggests that the composition and diversity of gut microbiota, crucial regulators of immune function, may influence the efficacy of vaccines. Against this backdrop, our study explores the complex interplay among SARS-CoV-2 inactivated vaccination, T2DM, and host microbiota. We discover that T2DM compromises the initial immune response to the SARS-CoV-2 inactivated vaccine, and this response is positively correlated with specific features of the gut microbiota, such as alpha diversity. We also demonstrate that the vaccination itself induces alterations in the composition and structure of the gut microbiota. These findings illuminate potential links between the gut microbiota and vaccine efficacy in individuals with T2DM, offering valuable insights that could enhance vaccine responses in this high-risk population.

Silicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16 S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites.

ABSTRACTBackground Epidemiological evidence has confirmed that periodontitis is an essential and independent risk factor of chronic obstructive pulmonary disease (COPD). Porphyromonas gingivalis, a major pathogen implicated in periodontitis, may make a vital contribution to COPD progression. However, the specific effects and molecular mechanism of the link between P. gingivalis and COPD are not clear.Methods and Results A COPD rat model was constructed by smoke exposure combined intratracheal instillation of E. coli-LPS, then P. gingivalis was introduced into the oral cavity of COPD rats. This research observed that lower lung function, more severe alveolar damage and inflammation occurred in COPD rats with P. gingivalis group. Meanwhile, P. gingivalis/gingipains could colonize the lung tissues and be enriched in bronchoalveolar lavage fluid (BALF) of COPD rats with P. gingivalis group, along with alterations in lung microbiota. Proteomic analysis suggested that Hsp90α/MLKL-meditated necroptosis pathway was up-regulated in P. gingivalis-induced COPD aggravation, the detection of Hsp90α and MLKL in serum and lung tissue verified that Hsp90α/MLKL was up-regulated.Conclusion These results indicate that P. gingivalis could emigrate into the lungs, alter lung microbiota and lead to aggravation of COPD, which Hsp90α/MLKL might participate in.

Purpose: Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut–lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM). Methods: 16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances. Results: In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC. Conclusion: Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut–lung communication. [ABSTRACT FROM AUTHOR]

ABSTRACT Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soil Bacillus subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides, while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheep’s blood agar inhibited the growth of Coccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth of Coccidioides to controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition of Coccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily included Lactobacillus and Staphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo.IMPORTANCECoccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%–80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%–10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.

It is increasingly recognized that interspecies interactions may modulate the pathogenicity of Pseudomonas aeruginosa during chronic lung infections. Nevertheless, while the interaction between P. aeruginosa and pathogenic microorganisms co-infecting the lungs has been widely investigated, little is known about the influence of other members of the lung microbiota on the infection process. In this study, we focused on investigating the impact of Prevotella species isolated from the sputum of people with cystic fibrosis (pwCF) on biofilm formation and virulence factor production by P. aeruginosa. Screening of a representative collection of Prevotella species recovered from clinical samples showed that several members of this genus (8 out 10 isolates) were able to significantly reduce biofilm formation of P. aeruginosa PAO1, without impact on growth. Among the tested isolates, the strongest biofilm-inhibitory activity was observed for Prevotella intermedia and Prevotella nigrescens, which caused a reduction of up to 90% in the total biofilm biomass of several P. aeruginosa isolates from pwCF. In addition, a strain-specific effect of P. nigrescens on the ability of P. aeruginosa to produce proteases and pyocyanin was observed, with significant alterations in the levels of these virulence factors detected in LasR mutant strains. Overall, these results suggest that non-pathogenic bacteria from the lung microbiota may regulate pathogenicity traits of P. aeruginosa, and possibly affect the outcome of chronic lung infections.

ABSTRACT Malignant central airway stenosis is treated with airway stent placement, but post-placement microbial characteristics remain unclear. We studied microbial features in 60 patients post-stent placement, focusing on changes during granulation tissue proliferation. Samples were collected before stent (N = 29), after stent on day 3 (N = 20), and after granulation tissue formation (AS-GTF, N = 43). Metagenomic sequencing showed significant respiratory tract microbiota changes with granulation tissue. The microbiota composition, dominated by Actinobacteria, Firmicutes, and Proteobacteria, was similar among the groups. At the species level, the AS-GTF group exhibited significant differences, with Peptostreptococcus stomatis and Achromobacter xylosoxidans enriched. Analysis based on tracheoesophageal fistula presence identified Tannerella forsythia and Stenotrophomonas maltophilia as the main differential species, enriched in the fistula subgroup. Viral and fungal detection showed Human gammaherpesvirus 4 and Candida albicans as the main species, respectively. These findings highlight microbiota changes after stent placement, potentially associated with granulation tissue proliferation, informing stent placement therapy and anti-infective treatment optimization.IMPORTANCEMalignant central airway stenosis is a life-threatening condition that can be effectively treated with airway stent placement. However, despite its clinical importance, the microbial characteristics of the respiratory tract following stent insertion remain poorly understood. This study addresses this gap by investigating the microbial features in patients with malignant central airway stenosis after stent placement, with a specific focus on microbial changes during granulation tissue proliferation. The findings reveal significant alterations in the diversity and structure of the respiratory tract microbiota following the placement of malignant central airway stents. Notably, certain bacterial species, including Peptostreptococcus stomatis and Achromobacter xylosoxidans, exhibit distinct patterns in the after-stent granulation tissue formation group. Additionally, the presence of tracheoesophageal fistula further influences the microbial composition. These insights provide valuable references for optimizing stent placement therapy and enhancing clinical anti-infective strategies.

Abstract Background Microbial communities are of critical importance in the human host. The lung and gut microbial communities represent the most essential microbiota within the human body, collectively referred to as the gut-lung axis. However, the differentiation between these communities and their influence on clinical outcomes in critically ill patients remains uncertain. Methods An observational cohort study was obtained in the intensive care unit (ICU) of an affiliated university hospital. Sequential samples were procured from two distinct anatomical sites, namely the respiratory and intestinal tracts, at two precisely defined time intervals: within 48 h and on day 7 following intubation. Subsequently, these samples underwent a comprehensive analysis to characterize microbial communities using 16S ribosomal RNA (rRNA) gene sequencing and to quantify concentrations of fecal short-chain fatty acids (SCFAs). The primary predictors in this investigation included lung and gut microbial diversity, along with indicator species. The primary outcome of interest was the survival status at 28 days following mechanical ventilation. Results Sixty-two mechanically ventilated critically ill patients were included in this study. Compared to the survivors, the diversity of microorganisms was significantly lower in the deceased, with a significant contribution from the gut-originated fraction of lung microorganisms. Lower concentrations of fecal SCFAs were detected in the deceased. Multivariate Cox regression analysis revealed that not only lung microbial diversity but also the abundance of Enterococcaceae from the gut were correlated with day 28 mortality. Conclusion Critically ill patients exhibited lung and gut microbial dysbiosis after mechanical ventilation, as evidenced by a significant decrease in lung microbial diversity and the proliferation of Enterococcaceae in the gut. Levels of fecal SCFAs in the deceased served as a marker of imbalance between commensal and pathogenic flora in the gut. These findings emphasize the clinical significance of microbial profiling in predicting the prognosis of ICU patients.

Background: Microbial communities are of critical importance in the human host. The lung and gut microbial communities represent the most essential microbiota within the human body, collectively referred to as the gut-lung axis. However, the differentiation between these communities and their influence on clinical outcomes in critically ill patients remains uncertain. Methods: An observational cohort study was obtained in the intensive care unit (ICU) of an affiliated university hospital. Sequential samples were procured from two distinct anatomical sites, namely the respiratory and intestinal tracts, at two precisely defined time intervals: within 48 h and on day 7 following intubation. Subsequently, these samples underwent a comprehensive analysis to characterize microbial communities using 16S ribosomal RNA (rRNA) gene sequencing and to quantify concentrations of fecal short-chain fatty acids (SCFAs). The primary predictors in this investigation included lung and gut microbial diversity, along with indicator species. The primary outcome of interest was the survival status at 28 days following mechanical ventilation. Results: Sixty-two mechanically ventilated critically ill patients were included in this study. Compared to the survivors, the diversity of microorganisms was significantly lower in the deceased, with a significant contribution from the gut-originated fraction of lung microorganisms. Lower concentrations of fecal SCFAs were detected in the deceased. Multivariate Cox regression analysis revealed that not only lung microbial diversity but also the abundance of Enterococcaceae from the gut were correlated with day 28 mortality. Conclusion: Critically ill patients exhibited lung and gut microbial dysbiosis after mechanical ventilation, as evidenced by a significant decrease in lung microbial diversity and the proliferation of Enterococcaceae in the gut. Levels of fecal SCFAs in the deceased served as a marker of imbalance between commensal and pathogenic flora in the gut. These findings emphasize the clinical significance of microbial profiling in predicting the prognosis of ICU patients. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that the lung microbiota is altered in critically ill patients and predicts clinical outcomes. Primary graft dysfunction (PGD) is a common complication and a leading cause of death within 1 month of lung transplantation, but the clinical significance of changes in the lung bacterial community during PGD is unclear. The aim of this study was to determine the contribution of the lung microbiota to the development and course of severe PGD. Methods: We conducted a retrospective study to characterize the lung microbiota of 32 lung transplant patients with combined PGD using next‐generation sequencing of bronchoalveolar lavage samples. The relationship between lung flora dysbiosis and lung immunity in PGD was assessed by quantification of alveolar cytokines. The contribution of microbiota characteristics to patient outcomes was assessed by estimating overall survival. Results: Patients diagnosed with PGD grade 3 showed a reduction in alpha diversity, driven by a significant increase in the abundance of the genera Modestobacter, Scardovia and Selenomonas, and a reduction in the proportion of the genera Klebsiella and Oribacterium. Alpha diversity of the lung microbiota in PGD3 patients was negatively correlated with BALF interleukin (IL)‐2 (r = ‐.752, p <.05). In addition, bacterial diversity in the lung microbiota of non‐survivors was lower than that of survivors (p =.041). Conclusions: There is variation in the lung microbiota of PGD grade 3 patients and dysbiosis of the lung microbiota is associated with lung immunity. The lung microbiota has potential in the diagnosis and treatment of PGD grade 3. [ABSTRACT FROM AUTHOR]

Introduction: Healthy lung microbiota plays an important role in preventing Mycobacterium tuberculosis (Mtb) infections by activating immune cells and stimulating production of T-helper cell type 1 cytokines. The dynamic stability of lung microbiota relies mostly on lung homeostasis. In our previous studies, we found that Mtb virulence factor, Rv1987 protein, can mediate host immune response and enhance mycobacterial survival in host lung. However, the alteration of lung microbiota and the contribution of lung microbiota dysbiosis to mycobacterial evasion in this process are not clear so far. Methods: M. smegmatis which does not contain the ortholog of Rv1987 protein was selected as a model strain to study the effects of Rv1987 on host lung microbiota. The lung microbiota, immune state and metabolites of mice infected by M. smegmatis overexpressing Rv1987 protein (MS1987) were detected and analyzed. Results: The results showed that Rv1987 inhibited inflammatory response in mouse lung and anaerobic bacteria and Proteobacteria, Bacteroidota, Actinobacteriota and Acidobacteriota bacteria were enriched in the lung tissues correspondingly. The immune alterations and microbiota dysbiosis affected host metabolic profiles, and some of significantly altered bacteria in MS1987-infected mouse lung, such as Delftia acidovorans, Ralstonia pickettii and Escherichia coli, led to anti-inflammatory responses in mouse lung. The secretory metabolites of these altered bacteria also influenced mycobacterial growth and biofilm formation directly. Conclusion: All these results suggested that Rv1987 can attenuate inflammatory response and alter microbiota in the lung, which in turn facilitates mycobacterial survival in the host. [ABSTRACT FROM AUTHOR]

Abstract Background The relationship between commensal microbiota and lung cancer (LC) has been studied extensively. However, developing replicable microbiological markers for early LC diagnosis across multiple populations has remained challenging. Current studies are limited to a single region, single LC subtype, and small sample size. Therefore, we aimed to perform the first large‐scale meta‐analysis for identifying micro biomarkers for LC screening by integrating gut and respiratory samples from multiple studies and building a machine‐learning classifier. Methods In total, 712 gut and 393 respiratory samples were assessed via 16 s rRNA amplicon sequencing. After identifying the taxa of differential biomarkers, we established random forest models to distinguish between LC populations and normal controls. We validated the robustness and specificity of the model using external cohorts. Moreover, we also used the KEGG database for the predictive analysis of colony‐related functions. Results The α and β diversity indices indicated that LC patients' gut microbiota (GM) and lung microbiota (LM) differed significantly from those of the healthy population. Linear discriminant analysis (LDA) of effect size (LEfSe) helped us identify the top‐ranked biomarkers, Enterococcus, Lactobacillus, and Escherichia, in two microbial niches. The area under the curve values of the diagnostic model for the two sites were 0.81 and 0.90, respectively. KEGG enrichment analysis also revealed significant differences in microbiota‐associated functions between cancer‐affected and healthy individuals that were primarily associated with metabolic disturbances. Conclusions GM and LM profiles were significantly altered in LC patients, compared to healthy individuals. We identified the taxa of biomarkers at the two loci and constructed accurate diagnostic models. This study demonstrates the effectiveness of LC‐specific microbiological markers in multiple populations and contributes to the early diagnosis and screening of LC.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease that greatly threatens human health. Studies have found that compared with the healthy population, the mucosal barrier function and immune homeostasis in COPD patients are impaired due to significantly changed composition and structure of both lung and gut microbiota, which further aggravate the disease progression. Taking measures to actively improve the microbial balance in lung and gut microbiota is very important for the prevention and delaying of the development of COPD. However, the summary and understanding of the role of lung and gut microbiota and their cross-talk mechanism in COPD still have much room for development. We reviewed the latest developments in the composition characteristics of lung and gut microbiota and the possible cross-talk mechanism between them in healthy people and COPD patients, as well as the prevention and treatment of COPD based on lung and gut microbiota and their cross-talk, providing new ideas for pathogenesis exploration, early diagnosis, prevention and treatment of COPD.

Abstract Background Specialized diets enriched with immune nutrients could be an important supplement in patients (pts) with acute traumatic brain injury (TBI). Omega-3 and arginine may interact with immune response and microbiota. No data are available about the role of the specialized diets in modulating the lung microbiota, and little is known about the influence of lung microbiota structure in development of ventilator-associated pneumonia (VAP) in TBI pts. The aims of this study are to evaluate the impact of specific nutrients on the lung microbiota and the variation of lung microbiota in TBI pts developing VAP. Methods A cohort of 31 TBI pts requiring mechanical ventilation in ICU was randomized for treatment with specialized (16pts) or standard nutrition (15pts). Alpha and beta diversity of lung microbiota were analyzed from bronco Alveolar Lavage (BAL) samples collected at admission and 7 days post-ICU admission in both groups. A further analysis was carried out on the same samples retrospectively grouped in VAP or no VAP pts. Results None developed VAP in the first week. Thereafter, ten out of thirty-one pts developed VAP. The BAL microbiota on VAP group showed significant differences in beta diversity and Staphylococcus and Acinetobacter Genera were high. The specialized nutrition had influence on beta diversity that reached statistical significance only in Bray–Curtis distance. Conclusion Our data suggest that TBI patients who developed VAP during ICU stay have different structures of BAL microbiota either at admission and at 7 days post-ICU admission, while no correlation has been observed between different enteral formulas and microbiota composition in terms of richness and evenness. These findings suggest that targeting the lung microbiota may be a promising approach for preventing infections in critically ill patients.

Abstract Background Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota. Results Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage. Conclusions Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. Video Abstract

Abstract Background Mammalian lungs comprise a complex microbial ecosystem that interacts with host physiology. Previous research demonstrates that the environment significantly contributes to bacterial community structure in the upper and lower respiratory tract. However, the influence of host genetics on the makeup of lung microbiota remains ambiguous, largely due to technical difficulties related to sampling, as well as challenges inherent to investigating low biomass communities. Thus, innovative approaches are warranted to clarify host-microbe interactions in the mammalian lung. Results Here, we aimed to characterize host genomic regions associated with lung bacterial traits in an advanced intercross mouse line (AIL). By performing quantitative microbial profiling (QMP) using the highly precise method of droplet digital PCR (ddPCR), we refined 16S rRNA gene amplicon-based traits to identify and map candidate lung-resident taxa using a QTL mapping approach. In addition, the two abundant core taxa Lactobacillus and Pelomonas were chosen for independent microbial phenotyping using genus-specific primers. In total, this revealed seven significant loci involving eight bacterial traits. The narrow confidence intervals afforded by the AIL population allowed us to identify several promising candidate genes related to immune and inflammatory responses, cell apoptosis, DNA repair, and lung functioning and disease susceptibility. Interestingly, one genomic region associated with Lactobacillus abundance contains the well-known anti-inflammatory cytokine Il10, which we confirmed through the analysis of Il10 knockout mice. Conclusions Our study provides the first evidence for a role of host genetic variation contributing to variation in the lung microbiota. This was in large part made possible through the careful curation of 16S rRNA gene amplicon data and the incorporation of a QMP-based methods. This approach to evaluating the low biomass lung environment opens new avenues for advancing lung microbiome research using animal models. Graphical Abstract

ABSTRACT: The dysbiosis of lung microbiota and inflammatory factors play a crucial role in the occurrence of lipopolysaccharides (LPS)-induced lung injury. Recently, mogroside V (MGV) has received increasing attention due to its potential health benefits in pneumonia, but its complex mechanism needs further experimental elucidation. In this study, we established an LPS-induced chicken lung injury model to investigate the protective effect of MGV on LPS-induced acute lung injury in broiler and its related mechanisms. A total of 192 one-day-old white-finned broilers were randomly assigned into 4 groups with 6 replicates: 1) control group: basal diet (d 1–44), saline (d 43); 2) LPS group: basal diet (d 1–44), LPS (d 43); 3) MGV group: basal diet + 0.2% MGV (d 1–44), saline (d 43); 4) MGV-LPS group: basal diet + 0.2% MGV (d 1–44), LPS (d 43). The results showed that pathological examination showed that lung tissue inflammation infiltration was reduced after MGV treatment. In addition, MGV can promote the balance of Th17 and Treg cell cytokines, significantly inhibit the expression of proinflammatory cytokines (IL-1β (P < 0.01), IL-6 (P < 0.001), IL-17F (P < 0.05)), and decrease immunosuppressive target expression (PD-L1 (P < 0.01), PD-1 (P < 0.001), RORα (P < 0.001)), activating the immune system. Furthermore, 16S rRNA sequencing analysis showed that MGV treatment could increase the abundance of beneficial bacteria in the lung and reduce the abundance of bacteria associated with inflammation. Generally, MGV intervention has a preventive effect on the pathological damage induced by lipopolysaccharides. Its mechanism is related to inhibiting the inflammatory response, regulating the Th17/Treg balance, and maintaining the stability of lung microbiota.

The Hylocereus undatus flower (HUF) is an herb with significant anti-inflammatory and immunomodulatory activity. It can be used as a food or a medicine and is beneficial to the gut and lung, which recent evidence has suggested interact through the gut–lung axis. This study investigated both the protective effect of HUF against DSS-induced colitis and its mechanism. The results showed that HUF significantly alleviated the symptoms of UC, maintained the normal functioning of the intestinal barrier, and ameliorated abnormally elevated inflammatory response, thereby repairing the damaged gut microenvironment and protecting the composition of the original gut microbiota. Interestingly, possibly related to the role of the gut–lung axis, HUF improved the disturbance of the lung microbiota and reduced lung injury in UC mice. To conclude, HUF alleviates colitis by restoring the integrity of the intestinal barrier, reducing the inflammatory response, and regulating gut and lung microbiota.

(1) Introduction: Although historically, the lung has been considered a sterile organ, recent studies through 16S rRNA gene sequencing have identified a substantial number of microorganisms. The human microbiome has been considered an "essential organ," carrying about 150 times more information (genes) than are found in the entire human genome. The purpose of the present study is to characterize and compare the microbiome in three different interstitial lung diseases: idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and nondifferential interstitial lung disease. (2) Material and methods: This was a prospective cohort study where the DNA of 28 patients with ILD was extracted from the lavage and then processed using the standard technique of 16S RNA gene sequencing. In a tertiary teaching hospital in the northern, western part of Romania, samples were collected through bronchoscopy and then processed. (3) Results: The same four species were found in all the patients but in different quantities and compositions: Firmicutes, Actinobacteria, Proteobacteria and Bacteroides. Streptococcus was the most prevalent genus, followed by Staphylococcus and Prevotella. Statistically significant differences in the OUT count for the ten most abundant taxa were found for the genus: Gemella, Actinobacteria, Prevotella, Neisseria, Haemophilus, and Bifidobacterium. The comparative analysis showed a richer microbiota in patients with IPF, as shown by the alpha diversity index. (4) Conclusions: In interstitial lung diseases, the microorganisms normally found in the lung are reduced to a restricted flora dominated by the Firmicutes family. These changes significantly disrupt the continuity of the observed bacterial pattern from the oropharynx to the bronchial tree and lung, possibly impacting the evolution and severity of interstitial lung diseases. [ABSTRACT FROM AUTHOR]

Background: The relationship between commensal microbiota and lung cancer (LC) has been studied extensively. However, developing replicable microbiological markers for early LC diagnosis across multiple populations has remained challenging. Current studies are limited to a single region, single LC subtype, and small sample size. Therefore, we aimed to perform the first large‐scale meta‐analysis for identifying micro biomarkers for LC screening by integrating gut and respiratory samples from multiple studies and building a machine‐learning classifier. Methods: In total, 712 gut and 393 respiratory samples were assessed via 16 s rRNA amplicon sequencing. After identifying the taxa of differential biomarkers, we established random forest models to distinguish between LC populations and normal controls. We validated the robustness and specificity of the model using external cohorts. Moreover, we also used the KEGG database for the predictive analysis of colony‐related functions. Results: The α and β diversity indices indicated that LC patients' gut microbiota (GM) and lung microbiota (LM) differed significantly from those of the healthy population. Linear discriminant analysis (LDA) of effect size (LEfSe) helped us identify the top‐ranked biomarkers, Enterococcus, Lactobacillus, and Escherichia, in two microbial niches. The area under the curve values of the diagnostic model for the two sites were 0.81 and 0.90, respectively. KEGG enrichment analysis also revealed significant differences in microbiota‐associated functions between cancer‐affected and healthy individuals that were primarily associated with metabolic disturbances. Conclusions: GM and LM profiles were significantly altered in LC patients, compared to healthy individuals. We identified the taxa of biomarkers at the two loci and constructed accurate diagnostic models. This study demonstrates the effectiveness of LC‐specific microbiological markers in multiple populations and contributes to the early diagnosis and screening of LC. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a common disorder, that burdens general well-being. Although the lung is connected to the upper respiratory tract, which is rich in microorganisms, no studies have reported the relationship between lung microbiota and AR. Mahuang Fuzi Xixin decoction (MFXD) is a traditional Chinese medicine (TCM) formula that is widely used to treat AR in the clinic but its underlying mechanism remains unclear. Hypothesis: We hypothesized that lung microbiota is associated with the pathogenesis of AR, and MFXD can improve AR by regulating microbiota dysbiosis. Methods: The ovalbumin-induced mouse AR model was used to evaluate the therapeutic effect of MFXD on AR. Then 16S rDNA amplicon sequencing, untargeted metabolomics, and other molecular biology technology were used to clarify the effects of MFXD on lung microbes dysbiosis and AR progression. Further, the human nasal epithelial cell line (HNEpCs) was used to evaluate the protective effect of MFXD on epithelial barrier damage caused by specific pathogens. Results: MFXD decreased plasma histamine and IgE levels, ameliorated pathological damage, and diminished the expression of tight junction proteins (ZO-1 and occludin) in lung and nasal tissues. MFXD altered AR-induced microbiota dysbiosis in the lungs and also plasma metabolites. Oral administration of MFXD altered microbiota dysbiosis in lung and AR-associated metabolic disorders. The dominant bacteria in the lungs of AR mice damaged the airway barrier, and MFXD reversed this change. Conclusion: This study revealed the correlation between the lung microbiota and AR in the mice model. We confirmed that lung microbiota plays a vital role in AR and that MFXD reduced damage to the epithelial barrier of the lungs and nasal mucosa by regulating lung microbiota and plasma metabolism imbalances. Our research provides a reference for the effect of lung microbiota on AR and provides a new idea for the treatment of AR. [ABSTRACT FROM AUTHOR]

Objective: In recent years, culture-independent methods led to provide a strong background to further microbiota studies, especially in lower respiratory tract investigation. Scientific research has focused more on studying and characterizing relationships between lung microbiota and various diseases, such as lung cancer, chronic obstructive pulmonary disease (COPD), asthma, sarcoidosis, acute respiratory infection, etc. Materials and Methods: The electronic search was performed on the PubMed database using the combination of the text words “respiratory microbiota” and “lung microbiome”. Only research studies in humans published between March 2022 and March 2023 were eligible for inclusion. Results: The scientific search retrieved 124 results, from which 106 articles were excluded if they duplicate or did not fit the inclusion criteria. A total of 18 studies were included for review. Conclusions: These studies have shown that changes in lower respiratory microbiota composition are a variable characteristic of all the aforementioned conditions; the relationship between circulating biomarkers, clinical data, and dysbiosis also was found in several studies. However, some studies had limitations, and future investigations are needed to better understand lung microbiota involvement in the pathogenesis of respiratory diseases.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a well-recognized cause of bacterial pneumonia in general. The gut microbiota and their metabolic byproducts act as important modulators of the gut-lung axis. Our investigation indicates a significant reduction in the abundance of butyrate producer unclassified_f__Lachnospiraceae within the lung and gut microbiota of MRSA-infected mice, as well as a significant decrease in the levels of butyrate in gut and serum. Additionally, supplementary sodium butyrate (NaB) significantly reduces bacteria colonization in the lung, suppresses pro-inflammatory cytokines expression, and enhances lung tissue morphology in MRSA-treated mice. The results of high-throughput 16S rDNA sequencing demonstrate that NaB reshapes the gut and lung microbiota by drastically reducing the abundance of potential pathogenic bacteria in the gut and cell motility-related bacteria in the lung, which are induced by MRSA. Moreover, NaB treatment augments the gut and circulating butyrate levels. Mechanistically, NaB promotes signal transducer and activator of transcription 1 (STAT1) acetylation and inhibits dimer STAT1 phosphorylation by reducing the binding of histone deacetylase 3 to STAT1, thereby altering alveolar macrophage polarization toward the M2 phenotype. Collectively, our findings suggest that NaB exerts a preventative effect against MRSA-induced pneumonia by enhancing the gut-lung microbiota and promoting macrophage polarization toward an anti-inflammatory M2 phenotype. The prophylactic administration of NaB emerges as a promising strategy for combating MRSA pneumonia. IMPORTANCE Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to carry a high burden in terms of mortality. With the roles of gut microbiota in mediating lung diseases being gradually uncovered, the details of the molecular mechanism of the “gut-lung axis” mediated by beneficial microorganisms and small-molecule metabolites have gradually attracted the attention of researchers. However, further studies are still necessary to determine the efficacy of microbial-based interventions. Our findings indicate that sodium butyrate (NaB) alleviates MRSA-induced pulmonary inflammation by improving gut-lung microbiota and promoting M2 polarization of alveolar macrophages. Therefore, the preventive administration of NaB might be explored as an effective strategy to control MRSA pneumonia.

ABSTRACT While the effect of gut microbiota and/or inflammation on a distant body site, including the lungs (gut–lung axis), has been well characterized, data about the influence of lung microbiota and lung inflammation on gut homeostasis (lung–gut axis) are scarce. Using a well-characterized model of pulmonary infection with the fungus Aspergillus fumigatus, we investigated alterations in the lung and gut microbiota by next-generation sequencing of the V3–V4 regions of total bacterial DNA. Pulmonary inflammation due to the fungus A. fumigatus caused bacterial dysbiosis in both lungs and gut, but with different characteristics. While increased alpha diversity and unchanged bacterial composition were noted in the lungs, dysbiosis in the gut was characterized by decreased alpha diversity indices and modified bacterial composition. The altered homeostasis in the lungs allows the immigration of new bacterial species of which 41.8% were found in the feces, indicating that some degree of bacterial migration from the gut to the lungs occurs. On the contrary, the dysbiosis occurring in the gut during pulmonary infection was a consequence of the local activity of the immune system. In addition, the alteration of gut microbiota in response to pulmonary infection depends on the bacterial composition before infection, as no changes in gut bacterial microbiota were detected in a rat strain with diverse gut bacteria. The data presented support the existence of the lung–gut axis and provide additional insight into this mechanism. IMPORTANCE Data regarding the impact of lung inflammation and lung microbiota on GIT are scarce, and the mechanisms of this interaction are still unknown. Using a well-characterized model of pulmonary infection caused by the opportunistic fungus Aspergillus fumigatus, we observed bacterial dysbiosis in both the lungs and gut that supports the existence of the lung–gut axis.

Background: The lung microbiome plays a crucial role in human health and disease. Extensive studies have demonstrated that the disturbance of the lung microbiome influences immune response, cognition, and behavior. The goal of this study was to investigate the effect of general anesthetics on lung microbiome. Methods: Eight-week-old male SD rats received a continuous intravenous infusion of propofol or inhalation of isoflurane for 4 h. 16S rRNA gene amplification from BALF samples was used to investigate the changes in the lung microbiome after interventions. We further performed neurobehavioral assessments to find the differential strains’ association with behavior disorder after isoflurane anesthesia. Results: The absolute and relative quantitation of 16S rRNA sequencing data showed that isoflurane altered the diversity and abundance of the lung microbiome in rats more than propofol. Elusimicrobia increased significantly in the isoflurane group. Both EPM and OFT results showed that rats exhibited depression-like behaviors after inhalation of isoflurane. In addition, significant differences were found in the COG/KO/MetaCyc/KEGG pathway enrichment analyses among the groups. Conclusion: Continuous inhalation of isoflurane changed the diversity and composition of the lung microbiota in rats, resulting in post-anesthesia depression.

Objective: The aim of this study is to explore the effects of early postnatal hyperoxia exposure combined with early ovalbumin (OVA) sensitization on lung inflammation and bacterial flora in neonatal mice on a juvenile mouse model of asthma. Methods: Thirty-two newborn female C57BL/6 J mice were randomly divided into four groups, which including room air+phosphate-buffered saline (PBS) group, hyperoxia+PBS group, room air+OVA group, and hyperoxia+OVA group, according to the hyperoxia exposure and/or OVA induction. Mice were exposed to either 95% O2 or room air for 7 days after birth; after 7 days, they were exposed to air and received an intraperitoneal injection of OVA suspension or PBS solution on postnatal days 21 (P21) and 28 (P28). From P36 to P42, the mice were allowed to inhale of 1% OVA or 0.9% NaCl solution. The mice were observed after the last excitation. HE staining was performed to observe the pathological changes in lung tissues. Wright-Giemsa staining was used to perform bronchoalveolar lavage fluid (BALF) leukocyte sorting. Enzyme-linked immunosorbent assay was used to determined the cytokines levels of interleukin (IL)-2, IL-5, IL-13, IL-17A, and IL-10 and serum IgE levels in BALF. Additionally, 16S rRNA sequencing was used to analyze the characteristics of lung microbiota. Results: Mice in the hyperoxia+OVA group showed asthma-like symptoms. HE staining results revealed a significant thickening of the airway wall and airway inflammation. BALF analysis of cellular components showed significant increases in total leukocyte and eosinophil counts and the levels of cytokines related to Th2 (IL-5 and IL-13) and Th17 (IL-17A); 16S rRNA sequencing revealed that the main members of the pulmonary microflora were Actinobacteriota, Proteobacteria, Firmicutes, and Bacteroidota at the phylum level. In addition, the bacteria with a major role were Acinetobacter and Moraxellaceae in the O2 + OVA group. Conclusion: The mouse suffering from postnatal hyperoxia exposure and early OVA sensitization, changes in symptoms, pathology, leukocyte and eosinophil counts, and levels of different T-cell cytokines in BALF and lung microbiota, which may provide a basis for the establishment of a juvenile mouse model of asthma. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19), primarily infects the respiratory and digestive tract. Several studies have indicated the alterations of the bacterial microbiome in the lower respiratory tract during viral infection. However, both bacterial and fungal microbiota in the lung of COVID-19 patients remained to be explored. Methods: In this study, we conducted nanopore sequencing analyses of the lower respiratory tract samples from 38 COVID-19 patients and 26 non-COVID-19 pneumonia controls. Both bacterial and fungal microbiome diversities and microbiota abundances in the lung were compared. Results: Our results revealed significant differences in lung microbiome between COVID-19 patients and non-COVID-19 controls, which were strongly associated with SARS-CoV-2 infection and clinical status. COVID-19 patients exhibited a notably higher abundance of opportunistic pathogens, particularly Acinetobacter baumannii and Candida spp. Furthermore, the potential pathogens enriched in COVID-19 patients were positively correlated with inflammation indicators. Conclusions: Our study highlights the differences in lung microbiome diversity and composition between COVID-19 patients and non-COVID-19 patients. This may contribute to predicting co-pathogens and selecting optimal treatments for respiratory infections caused by SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Specialized diets enriched with immune nutrients could be an important supplement in patients (pts) with acute traumatic brain injury (TBI). Omega-3 and arginine may interact with immune response and microbiota. No data are available about the role of the specialized diets in modulating the lung microbiota, and little is known about the influence of lung microbiota structure in development of ventilator-associated pneumonia (VAP) in TBI pts. The aims of this study are to evaluate the impact of specific nutrients on the lung microbiota and the variation of lung microbiota in TBI pts developing VAP. Methods: A cohort of 31 TBI pts requiring mechanical ventilation in ICU was randomized for treatment with specialized (16pts) or standard nutrition (15pts). Alpha and beta diversity of lung microbiota were analyzed from bronco Alveolar Lavage (BAL) samples collected at admission and 7 days post-ICU admission in both groups. A further analysis was carried out on the same samples retrospectively grouped in VAP or no VAP pts. Results: None developed VAP in the first week. Thereafter, ten out of thirty-one pts developed VAP. The BAL microbiota on VAP group showed significant differences in beta diversity and Staphylococcus and Acinetobacter Genera were high. The specialized nutrition had influence on beta diversity that reached statistical significance only in Bray–Curtis distance. Conclusion: Our data suggest that TBI patients who developed VAP during ICU stay have different structures of BAL microbiota either at admission and at 7 days post-ICU admission, while no correlation has been observed between different enteral formulas and microbiota composition in terms of richness and evenness. These findings suggest that targeting the lung microbiota may be a promising approach for preventing infections in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota. Results: Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage. Conclusions: Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. AFd3CvqLfCjKZ9n4H93NFT Video Abstract [ABSTRACT FROM AUTHOR]

Background: Mammalian lungs comprise a complex microbial ecosystem that interacts with host physiology. Previous research demonstrates that the environment significantly contributes to bacterial community structure in the upper and lower respiratory tract. However, the influence of host genetics on the makeup of lung microbiota remains ambiguous, largely due to technical difficulties related to sampling, as well as challenges inherent to investigating low biomass communities. Thus, innovative approaches are warranted to clarify host-microbe interactions in the mammalian lung. Results: Here, we aimed to characterize host genomic regions associated with lung bacterial traits in an advanced intercross mouse line (AIL). By performing quantitative microbial profiling (QMP) using the highly precise method of droplet digital PCR (ddPCR), we refined 16S rRNA gene amplicon-based traits to identify and map candidate lung-resident taxa using a QTL mapping approach. In addition, the two abundant core taxa Lactobacillus and Pelomonas were chosen for independent microbial phenotyping using genus-specific primers. In total, this revealed seven significant loci involving eight bacterial traits. The narrow confidence intervals afforded by the AIL population allowed us to identify several promising candidate genes related to immune and inflammatory responses, cell apoptosis, DNA repair, and lung functioning and disease susceptibility. Interestingly, one genomic region associated with Lactobacillus abundance contains the well-known anti-inflammatory cytokine Il10, which we confirmed through the analysis of Il10 knockout mice. Conclusions: Our study provides the first evidence for a role of host genetic variation contributing to variation in the lung microbiota. This was in large part made possible through the careful curation of 16S rRNA gene amplicon data and the incorporation of a QMP-based methods. This approach to evaluating the low biomass lung environment opens new avenues for advancing lung microbiome research using animal models. [ABSTRACT FROM AUTHOR]

The most common genetic hereditary disease affecting Caucasians is cystic fibrosis (CF), which is caused by autosomal recessive mutations in the CFTR gene. The most serious consequence is the production of a thick and sticky mucus in the respiratory tract, which entraps airborne microorganisms and facilitates colonization, inflammation and infection. Therefore, the present article compiles the information about the microbiota and, particularly, the inter-kingdom fungal-bacterial interactions in the CF lung, the molecules involved and the potential effects that these interactions may have on the course of the disease. Among the bacterial compounds, quorum sensing-regulated molecules such as homoserine lactones, phenazines, rhamnolipids, quinolones and siderophores (pyoverdine and pyochelin) stand out, but volatile organic compounds, maltophilin and CF-related bacteriophages are also explained. These molecules exhibit diverse antifungal mechanisms, including iron starvation and induction of reactive oxygen and nitrogen species production. The fungal compounds are less studied, but they include cell wall components, siderophores, patulin and farnesol. Despite the apparent competition between microorganisms, the persistence of significant rates of bacterial-fungal co-colonization in CF suggests that numerous variables influence it. In conclusion, it is crucial to increase scientific and economic efforts to intensify studies on the bacterial-fungal inter-kingdom interactions in the CF lung. [ABSTRACT FROM AUTHOR]

Anti-PD-1 antibody-mediated activation of type 17 T-cells undermines checkpoint inhibitor therapy in the LSL-KrasG12D murine lung cancer model. Herein, we establish that the Th17 subset is the primary driver of resistance to therapy demonstrate that the ontogeny of dysplasia-associated Th17 cells is driven by microbiota-conditioned macrophages; and identify the IL-17-COX-2-PGE2 axis as the mediator of CD8+ cytotoxic T-lymphocyte de-sensitization to checkpoint inhibitor therapy. Specifically, anti-PD-1 treatment of LSL-KrasG12D mice, in which CD4+ T-cells were deficient for RORc, resulted in a 60% increase in CTL cytotoxicity and a 2.5-fold reduction in tumor burden confirming the critical role of Th17 cells in resistance to therapy. Lung-specific depletion of microbiota reduced Th17 cell prevalence and tumor burden by 5- and 2.5-fold, respectively; establishing a link between microbiota and Th17 cell-driven tumorigenesis. Importantly, lung macrophages from microbiota sufficient, but not from microbiota-deficient, mice polarized naïve CD4+ T-cells to a Th17 phenotype, highlighting their role in bridging microbiota and Th17 immunity. Further, treatment with anti-PD-1 enhanced COX-2 and PGE2 levels, whereas neutralization of IL-17 diminished this effect. In contrast, inhibition of COX-2 rescued CTL activity and restored tumor suppression in anti-PD-1-treated mice, revealing the molecular basis of IL-17-mediated resistance to checkpoint blockade. Clinical implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Anti-PD-1 antibody-mediated activation of type 17 T-cells undermines checkpoint inhibitor therapy in the LSL-KrasG12D murine lung cancer model. Herein, we establish that the Th17 subset is the primary driver of resistance to therapy demonstrate that the ontogeny of dysplasia-associated Th17 cells is driven by microbiota-conditioned macrophages; and identify the IL-17-COX-2-PGE2 axis as the mediator of CD8+ cytotoxic T-lymphocyte de-sensitization to checkpoint inhibitor therapy. Specifically, anti-PD-1 treatment of LSL-KrasG12D mice, in which CD4+ T-cells were deficient for RORc, resulted in a 60% increase in CTL cytotoxicity and a 2.5-fold reduction in tumor burden confirming the critical role of Th17 cells in resistance to therapy. Lung-specific depletion of microbiota reduced Th17 cell prevalence and tumor burden by 5- and 2.5-fold, respectively; establishing a link between microbiota and Th17 cell-driven tumorigenesis. Importantly, lung macrophages from microbiota sufficient, but not from microbiota-deficient, mice polarized naïve CD4+ T-cells to a Th17 phenotype, highlighting their role in bridging microbiota and Th17 immunity. Further, treatment with anti-PD-1 enhanced COX-2 and PGE2 levels, whereas neutralization of IL-17 diminished this effect. In contrast, inhibition of COX-2 rescued CTL activity and restored tumor suppression in anti-PD-1-treated mice, revealing the molecular basis of IL-17-mediated resistance to checkpoint blockade. Clinical implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Resumen: La evidencia científica durante las últimas 2 décadas respalda que la aplicación de técnicas de cribado de cáncer de pulmón mediante tomografía computarizada (TC) de tórax de baja dosis de radiación contribuye a una reducción significativa de la mortalidad, gracias al diagnóstico en estadios potencialmente curativos. En referencia a dicho diagnóstico, existen además métodos novedosos en estudio, como la biopsia líquida, la identificación del microbioma pulmonar y la utilización de técnicas de inteligencia artificial, que desempeñarán un papel clave en un futuro próximo. En la actualidad, existe una tendencia hacia el tratamiento con cirugías cada vez menos invasivas (segmentectomía vs. lobectomía) basada en 2 ensayos clínicos recientes en tumores periféricos menores de 2 cm. A pesar de mostrar similar supervivencia, todavía existe controversia debido a la incertidumbre en cuanto a la tasa de recidiva y reserva funcional. En cuanto a la terapia adyuvante, la inmunoterapia sola o combinada con quimioterapia ofrece resultados alentadores en estadios resecables del cáncer de pulmón localmente avanzado, con respuestas patológicas completas y mejoría en la supervivencia. Tras el tratamiento con cirugía, a pesar de que no hay evidencia sólida del seguimiento a largo plazo de estos pacientes, en la práctica clínica se recomienda la realización de TC periódicas durante los primeros años.En conclusión, en el cáncer de pulmón existen avances importantes, que han mejorado las técnicas diagnósticas utilizando nuevas tecnologías y programas de cribado. Además, el tratamiento de este cáncer cada vez es más personalizado y todo ello se traduce en una mejora de la supervivencia de los pacientes. Abstract: Over the past 2 decades, scientific evidence has strongly supported the use of low-radiation dose chest computed tomography (CT) as a screening technique for lung cancer. This approach has resulted in a significant reduction in mortality rates by enabling the detection of early-stage lung cancer amenable to potentially curative treatments. Regarding diagnosis, there are also novel methods under study, such as liquid biopsy, identification of the pulmonary microbiome, and the use of artificial intelligence techniques, which will play a key role in the near future. At present, there is a growing trend towards less invasive surgical procedures, such as segmentectomy, as an alternative to lobectomy. This procedure is based on 2 recent clinical trials conducted on peripheral tumors measuring less than 2 cm. Although these approaches have demonstrated comparable survival rates, there remains controversy due to uncertainties surrounding recurrence rates and functional capacity preservation. With regard to adjuvant therapy, immunotherapy, either as a monotherapy or in conjunction with chemotherapy, has shown encouraging results in resectable stages of locally advanced lung cancer, demonstrating complete pathologic responses and improved overall survival.After surgery treatment, despite the lack of solid evidence for long-term follow-up of these patients, clinical practice recommends periodic CT scans during the early years.In conclusion, there have been significant advances in lung cancer that have improved diagnostic techniques using new technologies and screening programs. Furthermore, the treatment of lung cancer is increasingly personalized, resulting in an improvement in the survival of patients.

Exposure to chemicals in many occupational and environmental settings has the capacity to significantly disturb the commensal microbiota that symbiotically reside in humans. However, much more is known about gut microbiota (GM) than lung microbiota (LM) due to the challenges of collecting LM samples. The advent of culture-independent methodologies has revealed the complex and dynamic community of microbes harbored by the respiratory tract. It is now being recognized that LM can directly impact immunity in a manner that can result in disease. Significant differences in community composition and diversity have been shown between the LM of diseased lungs and those of healthy subjects. Studies have linked LM dysbiosis with human diseases such as idiopathic pulmonary fibrosis, lung inflammation, chronic obstructive pulmonary disease (COPD), asthma, and lung cancer. However, it is not known whether LM dysbiosis initiates/promotes disease pathogenesis or is merely a biomarker of disease. Many chronic lung diseases often occur together with chronic GIT diseases in what is termed as the gut–lung axis. The LM also affects the CNS, in the bidirectional lung–brain axis, through a number of potential mechanisms that include the direct translocation of micro-organisms. Chemically induced LM dysbiosis appears to play a significant part in human diseases as has been shown to arise due to air pollution, cigarette smoking, and the use of chemical antibiotics.

Pulmonary fibrosis is an irreversible disease, and its mechanism is unclear. The lung is a vital organ connecting the respiratory tract and the outside world. The changes in lung microbiota affect the progress of lung fibrosis. The latest research showed that lung microbiota differs in healthy people, including idiopathic pulmonary fibrosis (IPF) and acute exacerbation-idiopathic pulmonary fibrosis (AE-IPF). How to regulate the lung microbiota and whether the potential regulatory mechanism can become a necessary targeted treatment of IPF are unclear. Some studies showed that immune response and lung microbiota balance and maintain lung homeostasis. However, unbalanced lung homeostasis stimulates the immune response. The subsequent biological effects are closely related to lung fibrosis. Core fucosylation (CF), a significant protein functional modification, affects the lung microbiota. CF regulates immune protein modifications by regulating key inflammatory factors and signaling pathways generated after immune response. The treatment of immune regulation, such as antibiotic treatment, vitamin D supplementation, and exosome micro-RNAs, has achieved an initial effect in clearing the inflammatory storm induced by an immune response. Based on the above, the highlight of this review is clarifying the relationship between pulmonary microbiota and immune regulation and identifying the correlation between the two, the impact on pulmonary fibrosis, and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

The lung is a complex and unique organ system whose biology is strongly influenced by environmental exposure, oxygen abundance, connection to extrapulmonary systems via a dense capillary network, and an array of immune cells that reside in the tissue at steady state. The lung also harbors a low biomass community of commensal microorganisms that are dynamic during both health and disease with the capacity to modulate regulatory immune responses during diseases such as cancer. Lung cancer is the third most common cancer worldwide with the highest mortality rate amongst cancers due to the difficulty of an early diagnosis. This review discusses the current body of work addressing the interactions between the lung microbiota and the immune system, and how these two components of the pulmonary system are linked to lung cancer development and outcomes. Bringing in lessons from broader studies examining the effects of the gut microbiota on cancer outcomes, we highlight many challenges and gaps in this nascent field. [ABSTRACT FROM AUTHOR]

Rationale: It remains unclear how gastroesophageal reflux disease (GERD) affects allograft microbial community composition in lung transplant recipients and its impact on lung allograft inflammation and function. Objectives: Our objective was to compare the allograft microbiota in lung transplant recipients with or without clinically diagnosed GERD in the first year after transplant and assess associations between GERD, allograft microbiota, inflammation, and acute and chronic lung allograft dysfunction (ALAD and CLAD). Methods: A total of 268 BAL samples were collected from 75 lung transplant recipients at a single transplant center every 3 months after transplant for 1 year. Ten transplant recipients from a separate transplant center provided samples before and after antireflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction, respectively, and inflammatory markers and bile acids were quantified. Measurements and Main Results: We observed a range of allograft community composition with three discernible types (labeled community state types [CSTs] 1--3). Transplant recipients with GERD were more likely to have CST1, characterized by high bacterial density and relative abundance of the oropharyngeal colonizing genera Prevotella and Veillonella. GERD was associated with more frequent transitions to CST1. CST1 was associated with lower inflammatory cytokine concentrations than pathogen-dominated CST3 across the range of microbial densities observed. Cox proportional hazard models revealed associations between CST3 and the development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and proinflammatory cytokines. Conclusions: GERD was associated with a high bacterial density, Prevotella- and Veillonella-dominated CST1. CST3, but not CST1 or GERD, was associated with inflammation and early development of ALAD and CLAD. Nissen fundoplication was associated with a reduction in microbial density in BAL fluid samples, especially the CST1- specific genus, Prevotella. [ABSTRACT FROM AUTHOR]

The oral and upper respiratory tracts are closely linked anatomically and physiologically with the lower respiratory tract and lungs, and the influence of oral and upper respiratory microbes on the lung microbiota is increasingly being recognized. However, the ecological process and individual heterogeneity of the oral and upper respiratory tract microbes shaping the lung microbiota remain unclear owing to the lack of controlled analyses with sufficient sample sizes. Here, the microbiomes of saliva, nasal cavity, oropharyngeal area, and bronchoalveolar lavage samples are profiled and the shaping process of multisource microbes on the lung microbiota is measured. It is found that oral and nasal microbial inputs jointly shape the lung microbiota by occupying different ecological niches. It is also observed that the spread of oral microbes to the lungs is heterogeneous, with more oral microbes entering the lungs being associated with decreased lung function and increased lung proinflammatory cytokines. These results depict the external shaping process of lung microbiota and indicate the great value of oral samples, such as saliva, in monitoring and assessing lung microbiota status in clinical settings. [ABSTRACT FROM AUTHOR]