Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation

Bernasconi, Eric; Pattaroni, Céline; Koutsokera, Angela; Pison, Christophe; Kessler, Romain; Benden, Christian; Soccal, Paola M.; Magnan, A.; Aubert, John‐David; Marsland, Benjamin J.; Nicod, Laurent P.

doi:10.1164/rccm.201512-2424oc

Cited by 107 publications

(116 citation statements)

References 36 publications

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“…47 In another set of studies from 112 patients post-lung transplantation, it was observed that a shift away from a Prevotella -dominant airway microbiome correlated with the development of inflammatory or remodeling profiles in macrophages. 46 Prevotella -high and -low community profiles have been noted in healthy subjects, 14,30 with the Prevotella- high profile being associated with enhanced “subclinical” lung inflammation, that is notable for enhanced expression of inflammatory cytokines and elevated Th-17 lymphocytes. 30,52 However, association studies do not determine the direction of causality and this data would be very consistent with a model where subclinical airway inflammation leads to higher levels of micro-aspirated Prevotella .…”

Section: Lung Microbiota and Immunitymentioning

confidence: 98%

“…It has been observed in a number of studies of humans and mice that the relative proportion of Gammaproteobacteria in the lungs increases during disease. 1,38,46 We have recently reviewed the role of inflammation in promoting the growth of P. aeruginosa in cystic fibrosis and inflamed airways. 38 Thus, one of the consequences of the upregulated host inflammatory response on mucosal surfaces is the production of terminal electron acceptors for anaerobic respiration that allow P. aeruginosa and other Gammaproteobacteria to grow, persist and outcompete all other microbial members on that surface.…”

Section: The Lung Microbiome and Inflammation: A Two-way Streetmentioning

confidence: 99%

“…53 However, as described earlier, chronic airway inflammation is ultimately associated with the emergence of Gammaproteobacteria dominated bacterial communities in the airways. 1,38,46 The inflammation-microbiome connection is a two-way street in that pulmonary inflammation in LPS/ elastase-treated mice (a model of COPD) has been reported to increase Pseudomonas spp. and reduce Prevotella spp.…”

Section: Lung Microbiota and Immunitymentioning

confidence: 99%

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The respiratory tract microbiome and lung inflammation: a two-way street

2017

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The lungs are not sterile or free from bacteria; rather, they harbor a distinct microbiome whose composition is driven by different ecological rules than for the gastrointestinal tract. During disease, there is often a shift in community composition towards Gammaproteobacteria, the bacterial class that contains many common lung-associated gram-negative “pathogens.” Numerous byproducts of host inflammation are growth factors for these bacteria. The extracellular nutrient supply for bacteria in the lungs, which is severely limited during health, markedly increases due to the presence of mucus and vascular permeability. While Gammaproteobacteria benefit from airway inflammation, they also encode molecular components that promote inflammation, potentially creating a cyclical inflammatory mechanism. In contrast, Prevotella species that are routinely acquired via microaspiration from the oral cavity may participate in immunologic homeostasis of the airways. v Areas of future research include determining for specific lung diseases (1) whether an altered lung microbiome initiates disease pathogenesis, promotes chronic inflammation, or is merely a marker of injury and inflammation, (2) whether the lung microbiome can be manipulated therapeutically to change disease progression, (3) what molecules (metabolites) generated during an inflammatory response promote cross-kingdom signaling, and (4) how the lung “ecosystem” collapses during pneumonia, to be dominated by a single pathogen.

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Section: Lung Microbiota and Immunitymentioning

confidence: 98%

Section: The Lung Microbiome and Inflammation: A Two-way Streetmentioning

confidence: 99%

Section: Lung Microbiota and Immunitymentioning

confidence: 99%

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The respiratory tract microbiome and lung inflammation: a two-way street

2017

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“…However, significant gaps remain in our understanding of the dynamics of lung microbial communities and how these dynamics influence host-microbe interactions. Recent evidence in mice 54 and human subjects 55 argues for a cross-talk between microbes and immune cells, whereby inflammation can shape the microbiota and vice versa . 56 …”

Section: Asthmamentioning

confidence: 99%

The microbiome in allergic disease: Current understanding and future opportunities—2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology

Huang

Marsland

Bunyavanich

et al. 2017

Journal of Allergy and Clinical Immunology

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292

270

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PRACTALL is a joint initiative of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology to provide shared evidence-based recommendations on cutting-edge topics in the field of allergy and immunology. PRACTALL 2017 is focused on what has been established regarding the role of the microbiome in patients with asthma, atopic dermatitis, and food allergy. This is complemented by outlining important knowledge gaps regarding its role in allergic disease and delineating strategies necessary to fill these gaps. In addition, a review of progress in approaches used to manipulate the microbiome will be addressed, identifying what has and has not worked to serve as a baseline for future directions to intervene in allergic disease development, progression, or both.

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“…Moreover, there is accumulating evidence that the immune state of the transplanted lung correlates with changes in the composition of the lung microbiota (Bernasconi et al, 2016;Charlson et al, 2012). High abundance of opportunistic pathogens such as members of the Staphylococcus and Pseudomonas genera have been linked to pro-inflammatory responses in the transplanted lung (Bernasconi et al, 2016;Erb-Downward et al, 2011), and also found in respiratory diseases such as COPD and asthma (Hilty et al, 2010;Mika et al, 2018). These bacteria activate macrophages and induce a strong inflammatory response after transplantation, reflected by high levels of tumor necrosis factor-α (TNFα) and cyclooxygenase-2 (COX2) (Bernasconi et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

A prevalent and culturable microbiota links ecological balance to clinical stability of the human lung after transplantation

Das

Bernasconi

Koutsokera

et al. 2020

Preprint

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There is accumulating evidence that the lower airway microbiota impacts lung health.However, the link between microbial community composition and lung homeostasis remains elusive. We combined amplicon sequencing and culturomics to characterize the viable bacterial community in 234 longitudinal bronchoalveolar lavage samples from 64 lung transplant recipients and established links to viral loads, host gene expression, lung function, and transplant health. We find that the lung microbiota post-transplant can be categorized into four distinct compositional states, 'pneumotypes'. The predominant 'balanced' pneumotype was characterized by a diverse bacterial community with moderate viral loads, and host gene expression profiles suggesting immune tolerance. The other three pneumotypes were characterized by being either microbiota-depleted, or dominated by potential pathogens, and were linked to increased immune activity, lower respiratory function, and increased risks of infection and rejection. Collectively, our findings establish a link between the lung microbial ecosytem, human lung function, and clinical stability post-transplant. Graphical abstract2015), we found that Bacteroidetes and Firmicutes followed by Proteobacteria and Actinobacteria are the most abundant phyla in the post-transplant lung (Figure 1B).Prevalence analysis across all BALF samples showed that the community composition is highly variable with only 22 OTUs shared by ≥50% of the samples (Figure S1B, Dataset S3).However, these 22 OTUs constituted 42 % of the total number of normalized reads, indicating that they are predominant members of the post-transplant lung microbiota (Figure 1C, Figure S1C, Table S2, Dataset S3). They belonged to the genera Prevotella7, Streptococcus, Porphyromonas and Rothia, the majority of which are also prevailing community members in completion of the clinical dataset, Julie Pernot for technical assistance, and the transplant patients for allowing their clinical data and BALF samples to be used for clinical research.

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Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation

Abstract: The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.

Cited by 107 publications

References 36 publications

The respiratory tract microbiome and lung inflammation: a two-way street

The respiratory tract microbiome and lung inflammation: a two-way street

The microbiome in allergic disease: Current understanding and future opportunities—2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology

A prevalent and culturable microbiota links ecological balance to clinical stability of the human lung after transplantation

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