Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease

Liang, Weijie; Yang, Yuqiong; Gong, Shenhai; Wei, Mingyuan; Ma, Yingfei; Feng, Rui; Gao, Jingyuan; Liu, Xiaomin; Tu, Fuyi; Ma, Wei; Yi, Xinzhu; Liang, Zhenyu; Wang, Fengyan; Wang, Lingwei; Chen, Dandan; Shu, Wen‐Sheng; Miller, Bruce E.; Tal‐Singer, Ruth; Donaldson, Gavin C.; Wedzicha, Jadwiga A.; Singh, Dave; Wilkinson, Tom; Brightling, Christopher E.; Chen, Rongchang; Zhong, Nanshan; Wang, Zhang

doi:10.1016/j.chom.2023.04.018

Cited by 30 publications

(14 citation statements)

References 90 publications

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“…The APEHE primary model's atmospheric compounds primarily bind to AKT1, with MMP9 and TLR4 acting as secondary binding agents, indicating a link to pneumonia. AKT1 is widely distributed throughout various human tissues, plays a crucial role in both broad-spectrum antiviral therapy include COVID-19 [ 139 ], chronic obstructive pulmonary disease (COPD) [ 140 ] and Cancer field [ 141 ].…”

Section: Resultsmentioning

confidence: 99%

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Is aromatic plants environmental health engineering (APEHE) a leverage point of the earth system?

2024

Heliyon

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Section: Resultsmentioning

confidence: 99%

“…It is worth mentioning that the Staphylococcus aureus employed in our study was sourced from the nasal cavity of seven-year-old children. The reduction of Staphylococcus aureus could potentially slow down the deterioration of lung function and decrease tissue damage in mice [ 176 ].…”

Section: Resultsmentioning

confidence: 99%

Is aromatic plants environmental health engineering (APEHE) a leverage point of the earth system?

2024

Heliyon

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“…54,61–65 We show that the transcriptional activity of BAL microbes is quite broad in patients with better clinical outcomes, raising the possibility that microbial metabolites might benefit airway health, as has been recently shown for the anti-apoptotic microbial metabolite indole-3-acetic acid (IAA). 21,66,67…”

Section: Discussionmentioning

confidence: 99%

Pulmonary microbiome and transcriptome signatures reveal distinct pathobiologic states associated with mortality in two cohorts of pediatric stem cell transplant patients

Zinter,

Dvorak,

Mayday

et al. 2023

Preprint

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Lung injury is a major determinant of survival after pediatric hematopoietic cell transplantation (HCT). A deeper understanding of the relationship between pulmonary microbes, immunity, and the lung epithelium is needed to improve outcomes. In this multicenter study, we collected 278 bronchoalveolar lavage (BAL) samples from 229 patients treated at 32 children’s hospitals between 2014-2022. Using paired metatranscriptomes and human gene expression data, we identified 4 patient clusters with varying BAL composition. Among those requiring respiratory support prior to sampling, in-hospital mortality varied from 22-60% depending on the cluster (p=0.007). The most common patient subtype, Cluster 1, showed a moderate quantity and high diversity of commensal microbes with robust metabolic activity, low rates of infection, gene expression indicating alveolar macrophage predominance, and low mortality. The second most common cluster showed a very high burden of airway microbes, gene expression enriched for neutrophil signaling, frequent bacterial infections, and moderate mortality. Cluster 3 showed significant depletion of commensal microbes, a loss of biodiversity, gene expression indicative of fibroproliferative pathways, increased viral and fungal pathogens, and high mortality. Finally, Cluster 4 showed profound microbiome depletion with enrichment of Staphylococci and viruses, gene expression driven by lymphocyte activation and cellular injury, and the highest mortality. BAL clusters were modeled with a random forest classifier and reproduced in a geographically distinct validation cohort of 57 patients from The Netherlands, recapitulating similar cluster-based mortality differences (p=0.022). Degree of antibiotic exposure was strongly associated with depletion of BAL microbes and enrichment of fungi. Potential pathogens were parsed from all detected microbes by analyzing each BAL microbe relative to the overall microbiome composition, which yielded increased sensitivity for numerous previously occult pathogens. These findings support personalized interpretation of the pulmonary microenvironment in pediatric HCT, which may facilitate biology-targeted interventions to improve outcomes.

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“…Nuclear magnetic resonance and high-resolution mass spectrometry are two main analytical techniques for metabolomics, with the latter coupled with liquid or gas chromatography. Given the central role of metabolites in bridging the activities of microbiome and host, metabolomics have been increasingly applied to the lung microbiome studies in recent years [29] , [35] , [36] , where numerous microbial metabolites were identified to interact with host immunity and influence disease phenotypes. Of note, it is generally difficult to differentiate the exact microbial or host origin of the metabolites if they can be produced by both microbiome and host.…”

Section: The Multi-omics For the Lung Microbiomementioning

confidence: 99%

“… Intranasal inoculation of two airway lactobacilli restored IAA and recapitulated its protective effects in mice. COPD a Liang et al 2023 [36] Sputum 181 COPD patients (UK), 61 COPD patients (Guangazhou, China) Metagenome, metabolome, transcriptome Airway dysbiosis at baseline associates with accelerated lung function decline in COPD patients. Staphylococcus aureus promotes lung function decline through homocysteine-AKT1-S100A8/A9 axis.…”

Section: Application Of Multi-omics To Microbiome Studies In Respirat...mentioning

confidence: 99%

The application of multi-omics in the respiratory microbiome: Progresses, challenges and promises

Gao,

Yi,

Wang

2023

Computational and Structural Biotechnology Journal

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Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease

Cited by 30 publications

References 90 publications

Is aromatic plants environmental health engineering (APEHE) a leverage point of the earth system?

Is aromatic plants environmental health engineering (APEHE) a leverage point of the earth system?

Pulmonary microbiome and transcriptome signatures reveal distinct pathobiologic states associated with mortality in two cohorts of pediatric stem cell transplant patients

The application of multi-omics in the respiratory microbiome: Progresses, challenges and promises

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