Beyond the organ: lung microbiome shapes transplant indications and outcomes.

OBJECTIVES: The lung microbiome plays a crucial role in the development of chronic lung diseases, which may ultimately lead to the need for lung transplantation. Also, perioperative results seem to be connected with altered lung microbiomes and its dynamic changes providing a possible target for optimizing short-term outcome after transplantation. METHODS: A literature review using MEDLINE, PubMed Central and Bookshelf was performed. RESULTS: Chronic lung allograft dysfunction (CLAD) seems to be influenced and partly triggered by changes in the pulmonary microbiome and dysbiosis, e.g. through increased bacterial load or abundance of specific species such as Pseudomonas aeruginosa. Additionally, the specific indications for transplantation, with their very heterogeneous changes and influences on the pulmonary microbiome, influence long term outcome.Next to composition and measurable bacterial load, dynamic changes in the allografts microbiome also possess the ability to alter long-term outcomes negatively. This review discusses the "new" microbiome after transplantation and the associations with direct postoperative outcome. With the knowledge of these principles the impact of alterations in the pulmonary microbiome in hindsight to CLAD and possible therapeutic implications are described and discussed. CONCLUSIONS: The aim of this review is to summarize the current literature regarding pre- and postoperative lung microbiomes and how they influence different lung diseases on their progression to failure of conservative treatment. This review provides a summary of current literature for centers looking for further options in optimizing lung transplant outcomes and highlights possible areas for further research activities investigating the pulmonary microbiome in connection to transplantation.

Patho-immunological mechanisms of atopic dermatitis: The role of the three major human microbiomes.

Atopic dermatitis (AD) is a genetically predisposed allergic inflammatory dermatosis with chronic, pruritic, and recurrent features. Patients with AD have dry and itchy skin, often accompanied by chronic eczematous lesions, allergic rhinitis, or asthma, which has a considerable impact on their daily lives. With advances in genome sequencing technology, it has been demonstrated that microorganisms are involved in this disease, and the microorganisms associated with AD are attracting considerable research attention. An increasing number of studies conducted in recent years have demonstrated that an imbalanced microbiome in AD patients has substantial impact on disease prognosis, and the causes are closely tied to various immune mechanisms. However, the involvement of microorganisms in the pathogenesis of AD remains poorly understood. In this paper, we review the advances in research on the immunological mechanisms of the skin microbiome, intestinal microbiome, and lung microbiome that are related to AD prognosis and immunotherapy protocols. It is hoped that this approach will lay the foundation for exploring the pathogenesis of and emerging treatments for AD.

The effects of different lung parts, age, and batches on the lung microbiota of healthy rats.

BACKGROUND: Rat models are valuable tools to study the lung microbiota in diseases. Yet the impacts of different lung parts, young and mature adult stages, and the different batches of the same conditions on the healthy rat lung microbiome have not been investigated. METHODS: The rat lung microbiome was analyzed to clarify the lung part-dependent and age-dependent differences and to evaluate the effects of several 'batch environmental factors' on normal rats, after eliminating potential contamination. RESULTS: The results showed that the contamination could be identified and excluded. The lung microbiome from left and right lung parts was very similar so one representative part could be used in the microbiome study. There were significantly different lung microbial communities between the young and mature adult groups, and also between the different feeding batches groups of the same repetitive feeding conditions, but a common lung microbiota characterized by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria as the most dominant phyla were present in all adult rats. It indicated that the experiment under the same condition of the same rats batch was needed to compare the difference in the lung microbiota and repeated experiments were necessary to confirm the results. CONCLUSION: These data represented that the lung bacterial communities were dynamic and rapidly susceptible to environmental influence, clustered strongly by age or different feeding batches but similar in the different lung tissue parts. This study improved the basic understanding of the potential effects on the lung microbiome of healthy rats.

Sex-specific alterations in the gut and lung microbiome of allergen-induced mice.

Introduction: Recent evidence has demonstrated that the microbiome is a driver of the underlying pathophysiological mechanisms of respiratory disease. Studies have indicated that bacterial metabolites produced in the gut and lung can impact lung inflammation and immune cell activity, affecting disease pathology. Despite asthma being a disease with marked sex differences, experimental work linking microbiomes and asthma has not considered the sex variable. Methods: To test the hypothesis that the lung and gut microbial composition impacts allergic lung inflammation in a sex-specific manner, we evaluated lung and gut microbiome alterations in a mouse model of allergic inflammation and assessed their association with lung function and inflammation phenotypes. For this, we exposed male and female adult C57BL/6J mice intranasally to 25 µg of a house dust mite extract mix (HDM) daily, or phosphate-buffered saline (PBS) as control, for 5 weeks (n = 4-6/group). DNA from fecal pellets collected before and after the 5-week treatment, and from lung tissue collected at endpoint, was extracted using the ZymoBIOMICS®-96 MagBead DNA Kit and analyzed to determine the 16S microbiome via Targeted Metagenomic Sequencing. Results: The HDM treatment induced a sex-specific allergic inflammation phenotype with significantly higher neutrophilia, lymphocytosis, inflammatory gene expression, and histopathological changes in females than males following exposure to HDM, but higher airway hyperresponsiveness (AHR) in males than females. In addition, sex-specific lung gene expression and associated pathways were identified HDM mix after challenge. These changes corresponded to sex-specific alterations in the gut microbiome, where the Firmicutes to Bacteroidetes ratio (F:B) was significantly reduced in fecal samples from only male mice after HDM challenge, and alpha diversity was increased in males, but decreased in females, after 5-weeks of HDM treatment. Discussion: Overall, our findings indicate that intranasal allergen challenge triggers sex-specific changes in both gut and lung microbiomes, and induces sex-specific lung inflammation, AHR, and lung inflammatory gene expression pathways, suggesting a contribution of the lung-gut axis in allergic airway disease.

Genome sequence of Lactobacillus johnsonii XZ17, isolated from a C57BL/6J mouse lung.

Lactobacillus johnsonii XZ17 was isolated from the lung homogenate of a healthy C57BL/6J mouse. XZ17 is diminished in the lungs of syngeneic bone marrow-transplanted recipient mice. Long-read sequencing of XZ17 yielded a single genome of 1,948,140 bp, with a GC content of 34.64%.

Bronchiectasis.

Non-cystic fibrosis bronchiectasis, a condition that remains relatively underrecognized, has garnered increasing research focus in recent years. This scientific interest has catalyzed advancements in diagnostic methodologies, enabling comprehensive clinical and molecular profiling. Such progress facilitates the development of personalized treatment strategies, marking a significant step toward precision medicine for these patients. Bronchiectasis poses significant diagnostic challenges in both clinical settings and research studies. While computed tomography (CT) remains the gold standard for diagnosis, novel alternatives are emerging. These include artificial intelligence-powered algorithms, ultra-low dose chest CT, and magnetic resonance imaging (MRI) techniques, all of which are becoming recognized as feasible diagnostic tools. The precision medicine paradigm calls for refined characterization of bronchiectasis patients by analyzing their inflammatory and molecular profiles. Research into the underlying mechanisms of inflammation and the evaluation of biomarkers such as neutrophil elastase, mucins, and antimicrobial peptides have led to the identification of distinct patient endotypes. These endotypes present variable clinical outcomes, necessitating tailored therapeutic interventions. Among these, eosinophilic bronchiectasis is notable for its prevalence and specific prognostic factors, calling for careful consideration of treatable traits. A deeper understanding of the microbiome's influence on the pathogenesis and progression of bronchiectasis has inspired a holistic approach, which considers the multibiome as an interconnected microbial network rather than treating pathogens as solitary entities. Interactome analysis therefore becomes a vital tool for pinpointing alterations during both stable phases and exacerbations. This array of innovative approaches has revolutionized the personalization of treatments, incorporating therapies such as inhaled mannitol or ARINA-1, brensocatib for anti-inflammatory purposes, and inhaled corticosteroids specifically for patients with eosinophilic bronchiectasis.

Las bronquiectasias no fibrosis quística han atraído una creciente atención en investigación. Este interés científico ha catalizado avances en las metodologías de diagnóstico, permitiendo realizar perfiles clínicos y moleculares integrales. Este progreso facilita el desarrollo de estrategias de tratamiento personalizadas y marca un paso significativo hacia la medicina de precisión.Desde el punto de vista diagnóstico, las bronquiectasias plantean desafíos importantes en entornos clínicos y de investigación. Si bien la TC es el gold standard, están surgiendo nuevas alternativas. Entre ellas, algoritmos de inteligencia artificial, TC de tórax de dosis ultrabajas y técnicas de resonancia magnética.La medicina de precisión aboga por la caracterización de pacientes mediante análisis de perfiles inflamatorios y moleculares. Las investigaciones sobre mecanismos subyacentes de inflamación y la evaluación de biomarcadores como la elastasa de neutrófilos, mucinas y péptidos antimicrobianos, han llevado a la identificación de endotipos de pacientes. Estos endotipos exhiben resultados clínicos variables, requiriendo intervenciones terapéuticas personalizadas. La bronquiectasia eosinofílica destaca por su prevalencia y factores pronósticos específicos, exigiendo consideración de los rasgos tratables.Una comprensión profunda de la influencia del microbioma en la patogénesis y progresión de las bronquiectasias inspira un enfoque holístico. Considera el multibioma como una red microbiana interconectada, no entidades solitarias. El análisis del interactoma se convierte en una herramienta vital para identificar alteraciones durante fases estables y exacerbaciones.Este conjunto de enfoques innovadores revoluciona la personalización de los tratamientos, incorporando terapias como manitol inhalado o ARINA-1, brensocatib con fines antiinflamatorios y corticosteroides inhalados específicos para pacientes con bronquiectasias eosinofílicas.

The Metabolic Potential of the Human Lung Microbiome.

The human lung microbiome remains largely underexplored, despite its potential implications in the pharmacokinetics of inhaled drugs and its involvement in lung diseases. Interactions within these bacterial communities and with the host are complex processes which often involve microbial small molecules. In this study, we employed a computational approach to describe the metabolic potential of the human lung microbiome. By utilizing antiSMASH and BiG-SCAPE software, we identified 1831 biosynthetic gene clusters for the production of specialized metabolites in a carefully compiled genome database of lung-associated bacteria and fungi. It was shown that RiPPs represent the largest class of natural products within the bacteriome, while NRPs constitute the largest class of natural products in the lung mycobiome. All predicted BGCs were further categorized into 767 gene cluster families, and a subsequent network analysis highlighted that these families are widely distributed and contain many uncharacterized members. Moreover, in-depth annotation allowed the assignment of certain gene clusters to putative lung-specific functions within the microbiome, such as osmoadaptation or surfactant synthesis. This study establishes the lung microbiome as a prolific source for secondary metabolites and lays the groundwork for detailed investigation of this unique environment.

Analysis of pulmonary microecology and clinical characteristics of patients carrying human herpesvirus.

Aim: To investigate the impact of human herpes virus (HHV) carriage on lung microbiota, and its correlation with clinical features and laboratory indicators in patients.Methods: Retrospective analysis was conducted on 30 outpatient lung infection cases, which were divided into HHV (n = 15) and non-HHV (n = 15) groups. mNGS detected microbial composition. Microbial diversity and abundance were tested using Shannon and Chao1 indices. Their relationship with laboratory indicators were explored.Results: Significant differences in microbial abundance and distribution were found between two groups (p < 0.05). Moreover, HHV group showed negative correlations (p < 0.05) between Prevotella, Porphyromonas, Streptococcus and basophil/eosinophil percentages.Conclusion: HHV carriage impacts lung microbiota, emphasizing the need for clinicians to pay attention to HHV reactivation in outpatient lung infection patients.

This study looked at how a common virus called human herpesvirus (HHV) affects the bacteria in our lungs. We wanted to see if HHV is linked to how sick we feel and what tests show. We split 30 people who had lung infections into two groups ­ 15 with HHV and 15 without ­ and checked how sick they felt, did some tests, and looked at the types of bacteria in their lungs. Both groups felt similarly sick and got better with medicine, but people with HHV had fewer of a certain type of blood cell. People with and without HHV also had different types of bacteria in their lungs. This study helps us understand why people get sick with lung infections and how to make them better. It might also help doctors decide how to treat people with lung infections.

Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis.

BACKGROUND: Excessive inflammation and recurrent airway infections characterize people with cystic fibrosis (pwCF), a disease with highly heterogeneous clinical outcomes. How the overall immune response is affected in pwCF, its relationships with the lung microbiome, and the source of clinical heterogeneity have not been fully elucidated. METHODS: Peripheral blood and sputum samples were collected from 28 pwCF and an age-matched control group. Systemic immune cell subsets and surface markers were quantified using multiparameter flow cytometry. Lung microbiome composition was reconstructed using metatranscriptomics on sputum samples, and microbial taxa were correlated to circulating immune cells and surface markers expression. RESULTS: In pwCF, we found a specific systemic immune profile characterized by widespread hyperactivation and altered frequencies of several subsets. These included substantial changes in B-cell subsets, enrichment of CD35+/CD49d+ neutrophils, and reduction in dendritic cells. Activation markers and checkpoint molecule expression levels differed from healthy subjects. CTLA-4 expression was increased in Tregs and, together with impaired B-cell subsets, correlated with patients' lung function. Concentrations and frequencies of key immune cells and marker expression correlated with the relative abundance of commensal and pathogenic bacteria in the lungs. CONCLUSION: The CF-specific immune signature, involving hyperactivation, immune dysregulation with alteration in Treg homeostasis, and impaired B-cell function, is a potential source of lung function heterogeneity. The activity of specific microbes contributes to disrupting the balance of the immune response. Our data provide a unique foundation for identifying novel markers and immunomodulatory targets to develop the future of cystic fibrosis treatment and management.

Microbial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis.

Polymicrobial infection of the airways is a hallmark of obstructive lung diseases such as cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Pulmonary exacerbations (PEx) in these conditions are associated with accelerated lung function decline and higher mortality rates. An understanding of the microbial underpinnings of PEx is challenged by high inter-patient variability in airway microbial community profiles. We analyzed bacterial communities in 880 CF sputum samples and developed microbiome descriptors to model community reorganization prior to and during 18 PEx. We identified two microbial dysbiosis regimes with opposing ecology and dynamics. Pathogen-governed PEx showed hierarchical community reorganization and reduced diversity, whereas anaerobic bloom PEx displayed stochasticity and increased diversity. A simulation of antimicrobial treatment predicted better efficacy for hierarchically organized communities. This link between PEx type, microbiome organization, and treatment success advances the development of personalized clinical management in CF and, potentially, other obstructive lung diseases.