The Lung Microbiome in Hematopoietic Stem Cell Transplant. Where the Money Lies

McVerry, Bryan J.; Morris, Alison

doi:10.1164/rccm.201806-1088ed

Cited by 4 publications

(5 citation statements)

References 5 publications

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“…in both healthy animals and humans (27,46). Furthermore, disease results in alterations of the lung microbiome, features of which, in turn, correlate with alveolar inflammation (32,47,48). Discriminating between causal links and bystander effect in pulmonary microbiota-host interactions has proven mechanistically difficult.…”

Section: Discussionmentioning

confidence: 99%

Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis

O’Dwyer

Ashley

Gurczynski

et al. 2019

Am J Respir Crit Care Med

244

263

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Rationale: Idiopathic pulmonary fibrosis (IPF) causes considerable global morbidity and mortality, and its mechanisms of disease progression are poorly understood. Recent observational studies have reported associations between lung dysbiosis, mortality, and altered host defense gene expression, supporting a role for lung microbiota in IPF. However, the causal significance of altered lung microbiota in disease progression is undetermined. Objectives: To examine the effect of microbiota on local alveolar inflammation and disease progression using both animal models and human subjects with IPF. Methods: For human studies, we characterized lung microbiota in BAL fluid from 68 patients with IPF. For animal modeling, we used a murine model of pulmonary fibrosis in conventional and germ-free mice. Lung bacteria were characterized using 16S rRNA gene sequencing with novel techniques optimized for low-biomass sample load. Microbiota were correlated with alveolar inflammation, measures of pulmonary fibrosis, and disease progression. Measurements and Main Results: Disruption of the lung microbiome predicts disease progression, correlates with local host inflammation, and participates in disease progression. In patients with IPF, lung bacterial burden predicts fibrosis progression, and microbiota diversity and composition correlate with increased alveolar profibrotic cytokines. In murine models of fibrosis, lung dysbiosis precedes peak lung injury and is persistent. In germ-free animals, the absence of a microbiome protects against mortality. Conclusions: Our results demonstrate that lung microbiota contribute to the progression of IPF. We provide biological plausibility for the hypothesis that lung dysbiosis promotes alveolar inflammation and aberrant repair. Manipulation of lung microbiota may represent a novel target for the treatment of IPF.

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Section: Discussionmentioning

confidence: 99%

Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis

O’Dwyer

Ashley

Gurczynski

et al. 2019

Am J Respir Crit Care Med

244

263

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“…Other studies have confirmed that the lung microbiota plays a key role in orchestrating the immune response in healthy animals and humans 32,33 . In addition, disease leads to changes in the lung microbiota, the characteristics of which are in turn associated with alveolar inflammation 34,35 . This suggests that although the lung flora does not cause infection in patients, it is associated with lung immunity.…”

Section: Discussionmentioning

confidence: 93%

“…32,33 In addition, disease leads to changes in the lung microbiota, the characteristics of which are in turn associated with alveolar inflammation. 34,35 This suggests that although the lung flora does not cause infection in patients, it is associated with lung immunity. The role of lung microbiota in the treatment and prediction of severe PGD needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

The role of lung microbiota in primary graft dysfunction in lung transplant recipients

Wu,

Huang,

et al. 2023

Clinical Transplantation

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BackgroundRecent 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.MethodsWe 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.ResultsPatients 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).ConclusionsThere 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.

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“… 39 The same lung microbiome is involved in acute respiratory distress syndrome (ARDS) and hematopoietic stem cell transplantation. 40 – 42 In 2019, COVID-19 spread worldwide, and the relationship between coronaviruses and microorganisms also became a hot topic. 43 Currently, lung cancer has become an emerging area of microbiome research; its development, metastasis, and prognosis are microbiome-related (Fig.…”

Section: History Of the Lung Microbiomementioning

confidence: 99%

Lung microbiome: new insights into the pathogenesis of respiratory diseases

Li,

Zhou

2024

Sig Transduct Target Ther

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The lungs were long thought to be sterile until technical advances uncovered the presence of the lung microbial community. The microbiome of healthy lungs is mainly derived from the upper respiratory tract (URT) microbiome but also has its own characteristic flora. The selection mechanisms in the lung, including clearance by coughing, pulmonary macrophages, the oscillation of respiratory cilia, and bacterial inhibition by alveolar surfactant, keep the microbiome transient and mobile, which is different from the microbiome in other organs. The pulmonary bacteriome has been intensively studied recently, but relatively little research has focused on the mycobiome and virome. This up-to-date review retrospectively summarizes the lung microbiome’s history, composition, and function. We focus on the interaction of the lung microbiome with the oropharynx and gut microbiome and emphasize the role it plays in the innate and adaptive immune responses. More importantly, we focus on multiple respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), fibrosis, bronchiectasis, and pneumonia. The impact of the lung microbiome on coronavirus disease 2019 (COVID-19) and lung cancer has also been comprehensively studied. Furthermore, by summarizing the therapeutic potential of the lung microbiome in lung diseases and examining the shortcomings of the field, we propose an outlook of the direction of lung microbiome research.

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The Lung Microbiome in Hematopoietic Stem Cell Transplant. Where the Money Lies

Cited by 4 publications

References 5 publications

Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis

Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis

The role of lung microbiota in primary graft dysfunction in lung transplant recipients

Lung microbiome: new insights into the pathogenesis of respiratory diseases

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