Search Results (109)

Background and objectives: Occupational and environmental inhalation exposures, including high-aspect-ratio carbon nanotubes, can trigger pulmonary fibrosis (PF). The relationship between exposure-specific fibrogenic pathways (granulomatous inflammation versus diffuse epithelial injury) and lung microbiome dysbiosis remains incompletely understood. We therefore compared lung microbiome alterations in rat PF models induced by multi-walled carbon nanotubes (MWCNTs) and bleomycin. Materials and Methods: Female Wistar rats received a single intratracheal instillation of vehicle, MWCNTs (750 μg/rat), or bleomycin (1 mg/rat). At day 28, fibrosis and inflammation were evaluated by histopathology and bronchoalveolar lavage fluid (BALF) profiling. Lung microbial communities were characterized by 16S rRNA gene sequencing (V3–V4). Seventeen lung samples passed stringent quality control and were analyzed (control n = 5; bleomycin n = 7; MWCNT n = 5). Results: Both agents induced PF with increased profibrotic signaling, but with distinct pathological signatures: MWCNTs produced localized granulomatous lesions and a robust neutrophilic response (25% of BALF cells), whereas bleomycin caused diffuse interstitial remodeling. Bleomycin increased microbial richness (alpha diversity; p < 0.05) and significantly shifted community structure (beta diversity; p < 0.05), while MWCNT exposure showed comparatively limited changes in global diversity. The relative abundance of Pseudogracilibacillus (including P. marinus) was higher in the bleomycin group than in controls, whereas Facklamia tabacinasalis and Corynebacterium maris were more abundant in the MWCNT group. Across samples, Proteobacteria abundance was inversely correlated with BALF TGF-β, MCP-1, and neutrophil proportion. At the species level, Pseudogracilibacillus marinus was positively correlated with BALF TGF-β, while Facklamia tabacinasalis and Corynebacterium maris were positively correlated with MCP-1, CINC-3, and neutrophil proportion (Spearman; p < 0.05). Conclusions: Mechanistically distinct fibrogenic exposures generate exposure-linked lung microbiome signatures that track with host inflammatory and profibrotic responses. These signatures may support biomarker development for environmentally and occupationally relevant PF and motivate longitudinal and functional studies to clarify causality. Full article

Background: The increasing use of electronic cigarettes (ECIGs), especially among youth, has raised concerns about the impact of vaping on oral health. While ECIGs are often marketed as a safer alternative, the existing literature suggests that their use may have detrimental effects on the pulmonary and cardiovascular systems. The oral cavity is the first point of contact for ECIG aerosol, and new reports link vaping to the onset of periodontal disease. It is critical to understand the potential effects of vaping on the oral microbiome, which affects systemic health. This study investigates how flavored E-liquids and commensal bacteria influence the growth of Porphyromonas gingivalis, a periodontal pathobiont, under planktonic and biofilm conditions. Methods: P. gingivalis was grown planktonically in the presence of the supernatants of four streptococcal species (Streptococcus gordonii, Streptococcus intermedius, Streptococcus mitis, and Streptococcus oralis) and flavored E-liquids (tobacco, menthol, cinnamon, strawberry, and blueberry) under anaerobic conditions. Multispecies biofilms, including all the species mentioned above and Fusobacterium nucleatum, were also grown anaerobically and quantified by crystal violet assays, qPCR, and CFU counts. Results: Although E-liquids inhibit P. gingivalis growth under planktonic conditions, the presence of commensal supernatants partially mitigates this effect. However, P. gingivalis growth in multispecies biofilms is increased by E-liquid treatments. Conclusions: This study highlights the enhanced growth of P. gingivalis as part of an oral microbial community in the presence of E-liquids. These results suggest that E-liquid-induced alterations in multispecies biofilms may contribute to the observed dysbiosis in vapers and the associated risk of oral diseases. Full article

Cryptococcus neoformans is a major fungal pathogen responsible for life-threatening meningitis, especially in immunocompromised individuals. Although the gut–lung axis is known to regulate immune responses in respiratory infections, its role in cryptococcosis remains unclear. This study aimed to define the dynamic changes in the gut and lung microbiota and their relationship with host immunity during C. neoformans infection. Using a mouse model, we found that pulmonary infection induced significant dysbiosis in both the lung and gut microbiota, marked by decreased beneficial commensals and increased opportunistic pathogens. Integrated analysis showed these microbial shifts were closely associated with distinct immune responses: lung dysbiosis correlated with a strong IL-17-mediated pulmonary inflammatory response, while gut dysbiosis was linked to systemic immune activation in the spleen. Functional metagenomic prediction further revealed widespread disruption in microbial metabolic pathways, including energy metabolism and biosynthesis, in both sites. Importantly, a positive correlation was observed between lung and gut dysbiosis, indicating an interconnected gut–lung axis during cryptococcosis. These findings demonstrate that C. neoformans infection causes coordinated disruptions in microbiota and immunity across the gut–lung axis, underscoring the microbiome as a critical modulator of host response and suggesting potential avenues for microbiome-targeted therapies. Full article

Background: Early identification of irreversible pulmonary vascular remodeling in congenital heart disease-associated pulmonary arterial hypertension (C-PAH) is critical for optimizing surgical timing. Current noninvasive diagnostic methods are inadequate, and the lung microbiome and metabolome may provide novel insights into disease progression. Methods: We analyzed bronchoalveolar lavage fluid (BALF) from 47 children, including those with C-PAH (n = 15), CHD without PAH (C-NPAH, n = 16), and healthy controls (n = 16), using 16S rRNA gene sequencing and untargeted metabolomics. Differential microbial taxa and metabolites were identified, and their interactions with clinical indicators were assessed via Random Forest (RF) and Mediation Analysis. Results: C-PAH patients exhibited airway microbial dysbiosis, characterized by an elevated Firmicutes/Bacteroidetes (F/B) ratio and increased abundance of g_Lactobacillus. Metabolomic profiling revealed 88 differential metabolites between C-PAH and controls, and 3 between C-PAH and C-NPAH. N1-methylnicotinamide (MNAM) and 2-piperidone emerged as potential biomarkers. Mediation analysis showed that g_Eikenella influenced PAH indirectly through 2-piperidone (β = −0.376, p = 0.026), indicating a microbe–metabolite–host interaction. Conclusions: Integrative microbiome–metabolome profiling of BALF reveals potential biomarkers for C-PAH. These findings provide exploratory evidence that microbial and metabolic biomarkers, particularly 2-piperidone and MNAM, hold potential for the early, noninvasive identification of irreversible pulmonary vascular remodeling, but require further validation in independent cohorts. Full article

Early-life respiratory syncytial virus (EL-RSV) infection has been implicated in long-term pulmonary disease in children. In these studies, neonatal BALB/c mice were infected at day 7 of life, leading to >35% losses in critical lung function, airway mucus metaplasia, and transcriptional hallmarks of mucus hypersecretion four weeks after RSV infection. While EL-RSV minimally reshaped the resident lung microbiota, it led to significant gut dysbiosis, including a long-term reduction of Proteobacteria that can be a source of protective metabolites related to barrier and immune function. Subsequent studies assessing whether a common infant antibiotic (ampicillin) could mitigate EL-RSV-induced lung alterations revealed further severe gut microbiome alterations and, on its own, later in life, recapitulated the full spectrum of RSV-associated alterations in lung function. Metagenomic inference showed that both RSV and ampicillin administered during early life reduced biosynthetic pathways for microbiome-derived metabolites, which are known to reinforce tight junctions, regulate inflammation, and preserve extracellular matrix elasticity. The shared loss of these metabolic programs provides a mechanistic bridge linking distinct early-life exposures to the microbiome changes and airway mechanical deficits later in life. Collectively, the data suggest that RSV and/or antibiotic-triggered gut dysbiosis is the primary insult that likely promotes improper lung maturation/repair through a metabolite-mediated mechanism and may suggest metabolite restoration as a strategy to promote proper developmental lung function. Full article

Background: Long COVID (LC) is a multi-system disorder with persistent symptoms following SARS-CoV-2 infection. The presence of SARS-CoV-2 in the oral cavity and periodontium raises questions about its potential impact on periodontal health. Methods: A comprehensive literature search was conducted in PubMed using terms related to LC (e.g., “long-COVID,” “post-acute sequelae of SARS-CoV-2 infection,” “PASC,” “post-COVID-19,” “long-haul COVID”) and oral/periodontal diseases (e.g., “periodontal disease,” “periodontitis,” “gingiva,” “oral disease,” “dental”), filtered for English-language full-text articles published from 2019 to 2024. The search yielded 260 articles, which were supplemented with targeted searches on pathogenesis, immune mechanisms, microbiome alterations, and clinical outcomes, resulting in approximately 248 studies included in this review. Results: LC exhibits systemic immunoinflammatory dysregulation, including neutrophil activation, elevated pro-inflammatory cytokines, and complement activation, overlapping with mechanisms implicated in periodontitis. LC also leads to gastrointestinal and pulmonary dysbiosis, with potential effects on oral microbial communities. Gingival epithelium and periodontal ligament cells express ACE2, which is increased in periodontitis, facilitating viral entry. LC has been associated with reactivation of herpesviruses, such as Epstein–Barr virus, which are linked to autoimmune disorders and periodontitis. Conclusions: LC may act as a systemic risk factor for periodontitis. This review provides the theoretical foundation for the interactions between LC and oral health and highlights priorities for future epidemiologic and mechanistic research to better understand these relationships. Full article

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection primarily caused by Mycobacterium avium complex (MAC) and Mycobacterium abscessus. These species differ markedly in antibiotic susceptibility and treatment response, yet the contribution of the respiratory microbiome to this clinical variability remains unclear. To date, however, comparative analyses of microbiome differences between MAC-PD and M. abscessus-PD and their associations with disease severity are limited. Methods: We conducted microbiome analysis of sputum from 37 patients with NTM-PD. Patients were antibiotic-naïve and classified into MAC-PD (n = 29) and M. abscessus-PD (n = 8) groups. Disease severity was determined using radiologic extent on chest computed tomography. Bacterial communities were profiled by 16S rRNA gene sequencing, and differential taxa and predicted functional pathways were analyzed using LEfSe and KEGG orthology databases. Results: Distinct microbiome profiles were observed between MAC-PD and M. abscessus-PD. Three anaerobic species—Porphyromonas pasteri, Fusobacterium periodonticum, and Prevotella nanceiensis—were significantly enriched in M. abscessus-PD (LDA effect size > 3, p < 0.05). Functional biomarker analysis revealed significant enrichment of the cobalamin (vitamin B12) biosynthesis pathway in patients with severe disease, while the C19/C18 steroid hormone biosynthesis pathway was enriched in those with mild disease (p < 0.05). Conclusions: In conclusion, our study demonstrates distinct differences in the respiratory microbiome between MAC-PD and M. abscessus-PD and identifies specific functional pathways associated with disease severity in NTM-PD. These findings highlight the potential value of microbial metabolic signatures as biomarkers for disease assessment. Full article

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants recognized for their toxicological significance. Increasing evidence suggests that chronic exposure to low-molecular-weight PAHs (LMW-PAHs) contributes to heightened disease vulnerability and immune dysregulation, particularly among rural female populations. Recent studies have further linked a significant association between PAH exposure and gut microbiome (GM) modifications. Considering the common embryonic origin of the intestinal and respiratory systems, cross-organ communication under conditions of PAH exposure warrants deeper exploration. Although current gut–lung axis research largely emphasizes microbial metabolites such as short-chain fatty acids and bile acids, the contribution of arachidonic acid (AA) metabolites in LMW-PAH-induced pulmonary inflammation via this axis remains poorly defined. To address this knowledge gap, we developed an animal model employing integrated 16S rRNA sequencing and metabolomics approaches to systematically examine phenanthrene (Phe) and fluorene (Flu) induced GM compositional shifts and associated metabolic reprogramming. Through comprehensive profiling, we identified candidate microorganisms and metabolites potentially involved in dysbiosis-mediated pulmonary inflammation, thereby elucidating the mechanistic basis of Phe and Flu-associated health risks. Full article

Objectives: This systematic review aimed to evaluate the association between oral health—particularly dental caries and dysbiosis of the oral microbiome—and respiratory diseases across different age groups and clinical settings, with emphasis on microbial overlap, clinical outcomes, and preventive strategies. Methods: A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, and the Cochrane Library up to June 2025. Eligible studies included randomized controlled trials, cohort, case–control, and cross-sectional investigations examining the relationship between oral diseases or microbiome alterations and respiratory outcomes. Data on study design, population, oral health parameters, microbial taxa, and respiratory endpoints were extracted. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT, 2018). Results: Twenty studies met the inclusion criteria, encompassing pediatric, adult, and elderly populations. Poor oral health, reflected by higher caries indices and periodontal inflammation, was consistently associated with increased risk of lower respiratory tract infections (LRTI), aspiration events, ventilator-associated pneumonia (VAP), and impaired pulmonary function. Oral microbiome analyses revealed enrichment of Veillonella, Prevotella, Klebsiella, and Pseudomonas species in both oral and airway samples, supporting the oral cavity as a reservoir for respiratory pathogens. Interventional evidence from intensive care and nursing home settings demonstrated that structured oral care—particularly daily toothbrushing and chlorhexidine-based plaque control—significantly reduced pneumonia incidence. Conclusions: This review confirms a clinically relevant and biologically plausible link between oral dysbiosis, dental caries, and respiratory disease. Oral biofilms contribute to infection risk through microaspiration and microbial seeding of the lower airways. Integrating oral screening, hygiene maintenance, and treatment of active oral disease into respiratory care pathways may reduce respiratory morbidity and mortality, particularly among high-risk populations such as ICU patients, older adults, and individuals with chronic lung disease. Full article

Background/Objectives: Acute lung injury (ALI) represents a life-threatening respiratory syndrome characterized by dysregulated pulmonary inflammation, alveolar-capillary barrier dysfunction, and gut-lung axis impairment. Although Lycium ruthenicum polysaccharide (LRP) possesses documented anti-inflammatory properties, its role in ALI remains systematically unexplored. This study aimed to investigate the protective effects of LRP against lipopolysaccharide (LPS)-induced ALI. Methods: In vitro, A549 cells were subjected to injury induction with 10 μg/mL LPS. In vivo, male C57BL/6J mice were randomly allocated to four groups and, respectively, administered 100 mg/kg LRP, 400 mg/kg LRP, or normal saline for 7 days prior to ALI induction via intratracheal LPS instillation (5 mg/kg). Results: LRP restored viability in LPS-injured A549 cells and attenuated their inflammatory responses. Histopathological analysis demonstrated that high-dose LRP (H-LRP) significantly reduced alveolar collapse and inhibited inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) compared to the LPS group. The H-LRP group exhibited marked downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) concomitant with upregulation of the anti-inflammatory cytokine IL-10. Intestinal microbiome sequencing confirmed LRP-mediated restoration of gut microbiota homeostasis, evidenced by a 2.2-fold increase in commensal Bacteroides and decreased abundance of pathogenic Escherichia-Shigella. Conclusions: These findings establish LRP as a protective agent against ALI and suggest its potential utility as an adjuvant therapeutic candidate for enhanced pulmonary protection. Full article

Background: The respiratory microbiota is pivotal in maintaining pulmonary health and modulating disease; however, the intricate interplay between smoking, lung cancer, and microbiome composition remains incompletely understood. Here, we characterized the lower respiratory tract microbiome in a Russian cohort of 297 individuals, comprising healthy subjects and lung cancer patients of different smoking statuses (current smokers, former smokers, and nonsmokers). Methods: Using next-generation sequencing of the 16S rRNA gene from unstimulated sputum samples, we identify distinct microbiota signatures linked to smoking and lung cancer. A PERMANOVA (Adonis) test and linear discriminant analysis effect size were used for statistical analysis of data. Results: In healthy individuals, smoking did not affect microbiome diversity but markedly altered its composition, characterized by an increase in Streptococcus and a reduction in Neisseria as well as other genera such as Fusobacterium, Alloprevotella, Capnocytophaga, and Zhouea. Healthy former smokers’ microbiota profiles closely resembled those of healthy nonsmokers. In lung cancer patients, microbiome diversity and composition were minimally impacted by smoking, possibly due to the dominant influence of tumor-microenvironment-related factors. Nevertheless, Neisseria abundance remained significantly lower in smokers across advanced-stage lung cancer. Lung cancer patients exhibited distinctive microbiota signatures, including enrichment of Flavobacteriia, Bacillales, and Pasteurellales and depletion of Alphaproteobacteria, Coriobacteriaceae, and Microbacteriaceae, irrespective of smoking status. Conclusions: Our findings emphasize the profound impact of smoking on healthy respiratory microbiota which may be masked by lung-cancer-related factors. These insights highlight the necessity of considering smoking status in microbiome studies to enhance the understanding of respiratory health and disease. Full article

Mycoplasmal pneumonia of sheep (MPS), caused by Mesomycoplasma (Mycoplasma) ovipneumoniae, profoundly impacts ovine productivity and survival. Although gut–lung microbiota interactions are increasingly recognized in respiratory diseases, whether similar crosstalk occurs between the lung and rumen microbiota in MPS-affected sheep remains unknown. To investigate alterations in the lung and rumen microbiota of sheep with MPS, the crosstalk between these microbial communities, and their impacts on growth phenotypes. From a cohort of 414 naturally infected six-month-old male Hu sheep, we selected 10 individuals with severe pulmonary pathology and 10 healthy controls for detailed phenotypic and microbiome analyses. Assessment of 359 phenotypic traits revealed that MPS significantly impairs feed efficiency and growth rate (p < 0.05). Through 16S rRNA gene sequencing, we found that MPS significantly altered the pulmonary microbiota community structure (p < 0.01), with a noticeable impact on the rumen microbiota composition (p = 0.059). Succinivibrionaceae_UCG-001 was significantly depleted in both the rumen and lungs of diseased sheep (p < 0.05) and strongly associated with reduced average daily feed intake (p < 0.05). In addition, pulmonary Pasteurella and ruminal Succinivibrionaceae_UCG-002 were significantly enriched in MPS-affected sheep, showed a strong positive correlation (p < 0.05), and were both negatively associated with feed efficiency (p < 0.05). Notably, Pasteurella multocida subsp. gallicida may act as a keystone species influencing feed efficiency. These findings point to a previously unrecognized rumen-lung microbial axis that may modulate host productivity in sheep affected by MPS. This work provides new insights into the pathogenesis of MPS and offers potential targets for therapeutic intervention and management. Full article

The lung microbiota is integral to maintaining microenvironmental homeostasis, influencing immune regulation, host defense against pathogens, and overall respiratory health. The dynamic interplay among the lung microbiota emphasizes their significance in shaping the respiratory milieu and potential impact on diverse pulmonary affections. This investigation aimed to identify the effects of invasive mechanical ventilation on the lung microbiome. Materials and Methods: A systematic review was conducted with registration number CRD42023461618, based on a search of PubMed, SCOPUS, and Web of Science databases, in line with the PRISMA guidelines. To achieve this, “(mechanical ventilation) AND (microbiota)” was used as the search term, replicable across all databases. The closing date of the search was 12 March 2025, and the evidence was scored using the MINORS scale. Results: A total of 16 studies were included, with patients aged 13.6 months to 76 years, predominantly male (64.2%). Common ICU admission diagnoses requiring invasive mechanical ventilation (IMV) included pneumonia, acute respiratory failure, and COVID-19. IMV was associated with reduced lung microbiota diversity and an increased prevalence of pathogenic bacteria, including Prevotella, Streptococcus, Staphylococcus, Pseudomonas, and Acinetobacter. The most frequently used antibiotics were cephalosporins, aminoglycosides, and penicillins. IMV-induced pulmonary dysbiosis correlated with higher infection risk and mortality, particularly in pneumonia and COVID-19 cases. Factors such as antimicrobial therapy, enteral nutrition, and systemic inflammation contributed to these alterations. Conclusions: Invasive mechanical ventilation has been associated with the development of alterations in the respiratory microbiome, resulting in reduced diversity of lung microorganisms. Full article

Pulmonary arterial hypertension (PAH) is an irreversible disease characterized by vascular and systemic inflammation, ultimately leading to right ventricular failure. There is a great need for adjunctive therapies to extend survival for PAH patients. The gut microbiome influences the host immune system and is a potential novel target for PAH treatment. We review the emerging preclinical and clinical evidence which strongly suggests that there is gut dysbiosis in PAH and that alterations in the gut microbiome may either initiate or facilitate the progression of PAH by modifying systemic immune responses. We also outline approaches to modify the intestinal microbiome and delineate some practical challenges that may impact efforts to translate preclinical microbiome findings to PAH patients. Finally, we briefly describe studies that demonstrate contributions of infections to PAH pathogenesis. We hope that this review will propel further investigations into the mechanisms by which gut dysbiosis impacts PAH and/or right ventricular function, approaches to modify the gut microbiome, and the impact of infections on PAH development or progression. Full article