N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction

Banday, Mudassir M; Kumar, Archit; Vestal, Grant; Sethi, Jaskaran; Patel, Kapil; O'Neill, Edward B.; Finan, Jon; Cheng, Feng; Lin, Muling; Davis, Nicole M.; Goldberg, Hilary J.; Coppolino, Antonio; Mallidi, Hari R.; Dunning, John; Visner, Gary; Gaggar, Amit; Seyfang, Andreas; Sharma, Nirmal

doi:10.1016/j.healun.2021.02.014

Cited by 8 publications

(4 citation statements)

References 49 publications

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“…Despite demonstrating changes in composition and increased bacterial burden, no one individual bacterial taxa was identified to be significantly associated with CLAD development or death [12 ▪ ]. A further study also highlighted that increased bacterial biomass in the lungs is associated with the development of CLAD, however, this paper went a step further to suggest that a Proteobacteria, and specifically a Pseudomonas, enriched airway microbiome may enhance epithelial to mesenchymal transition of airway cells [13 ▪ ], thus presenting an underlying mechanism for the development of chronic rejection. There exists a complex interplay between microbial species in the lung and the host responses, all of which present opportunities for intervention in attempts to reduce the development of CLAD in lung transplant recipients.…”

Section: The Lung Microbiome and Chronic Lung Allograft Dysfunctionmentioning

confidence: 86%

The pulmonary microbiome: recent advances in understanding its role in chronic lung allograft dysfunction

Mitchell

Glanville

2022

Current Opinion in Organ Transplantation

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Purpose of reviewLung transplantation presents a rescue therapy for those with end-stage lung disease. Survival in lung transplant patients remains limited due to chronic lung allograft dysfunction (CLAD), a range of pathologic manifestations leading to graft loss. The mechanisms underlying CLAD remain poorly understood, and the lung microbiome has been suggested as a potential contributor to this condition. This review aims to explore how the pulmonary microbiome is impacted by lung transplantation, and how alterations in this microbiome may contribute to the pathogenesis of CLAD.Recent findingsThe pulmonary microbiome is made up of a range of microorganisms, and it varies considerably in lung transplant patients when compared with healthy controls. The lung microbiome changes over the early transplant period, and the composition of species appears to have an impact on inflammatory responses within the lungs. A number of studies have shown that an increase in bacterial biomass in the allograft, and enrichment with the genera Proteobacteria, or more specifically, Pseudomonas species, is associated with CLAD.SummaryThis area of research is still in its infancy; however, the suggestion that changes in the composition of the microbiome and enrichment with certain species may predispose to the pathologic changes that underlie CLAD indicate that modulation of the microbiome may be of use in potential future therapeutics.

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Section: The Lung Microbiome and Chronic Lung Allograft Dysfunctionmentioning

confidence: 86%

The pulmonary microbiome: recent advances in understanding its role in chronic lung allograft dysfunction

Mitchell

Glanville

2022

Current Opinion in Organ Transplantation

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“…and reduced Prevotella spp. was found [28]. In contrast, another study found no difference in the microbial composition in CLAD (phenotypes) but described a significant correlation between microbiota composition, overall diversity, and levels of inflammatory cytokines in bronchoalveolar lavage, particularly CXCL8 [29].…”

Section: Chronic Lung Allograft Dysfunction: Is There a Need For A Bi...mentioning

confidence: 93%

Novel biomarkers of chronic lung allograft dysfunction: is there anything reliable?

Verleden

2021

Current Opinion in Organ Transplantation

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Purpose of reviewChronic lung allograft dysfunction (CLAD) remains a major barrier preventing long-term survival following lung transplantation. As our clinical knowledge regarding its definition and presentation has significantly improved over the last years, adequate biomarkers to predict development of CLAD, phenotype of CLAD or prognosis post-CLAD diagnosis are definitely needed. Recent findingsRadiological and physiological markers are gradually entering routine clinical practice. In-depth investigation of biological samples including broncho-alveolar lavage, biopsy and serum has generated potential biomarkers involved in fibrogenesis, airway injury and inflammation but none of these are universally accepted or implemented although progress has been made, specifically regarding donorderived cell-free DNA and donor-specific antibodies.

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“…54 Another study found that CLAD is associated with increased bacterial biomass and a Proteobacteria-enriched airway microbiome and epithelial to mesenchymal transition via N-myc-interactor expression. 55 Other studies, however, failed in pinpointing a certain pathogen to be responsible for the increased risk of CLAD. Indeed, Combs et al 56 showed that the microbial composition 1-y posttransplant was different in patients who will die or develop CLAD in the next 500 days compared with CLAD-free and surviving patients but could not relate this to a difference in individual bacterial taxa.…”

Section: Markers In Bronchoalveolar Lavagementioning

confidence: 99%

Biomarkers for Chronic Lung Allograft Dysfunction: Ready for Prime Time?

et al. 2022

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Chronic lung allograft dysfunction (CLAD) remains a major hurdle impairing lung transplant outcome. Parallel to the better clinical identification and characterization of CLAD and CLAD phenotypes, there is an increasing urge to find adequate biomarkers that could assist in the earlier detection and differential diagnosis of CLAD phenotypes, as well as disease prognostication. The current status and state-of-the-art of biomarker research in CLAD will be discussed with a particular focus on radiological biomarkers or biomarkers found in peripheral tissue, bronchoalveolar lavage‚ and circulating blood‚ in which significant progress has been made over the last years. Ultimately, although a growing number of biomarkers are currently being embedded in the follow-up of lung transplant patients, it is clear that one size does not fit all. The future of biomarker research probably lies in the rigorous combination of clinical information with findings in tissue, bronchoalveolar lavage‚ or blood. Only by doing so, the ultimate goal of biomarker research can be achieved, which is the earlier identification of CLAD before its clinical manifestation. This is desperately needed to improve the prognosis of patients with CLAD after lung transplantation.

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N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction

Cited by 8 publications

References 49 publications

The pulmonary microbiome: recent advances in understanding its role in chronic lung allograft dysfunction

The pulmonary microbiome: recent advances in understanding its role in chronic lung allograft dysfunction

Novel biomarkers of chronic lung allograft dysfunction: is there anything reliable?

Biomarkers for Chronic Lung Allograft Dysfunction: Ready for Prime Time?

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