Mycobiote and Microbiote in Lungs

Group leader Laurence Delhaes

As other mucosal sites of human body, respiratory tract hosts a specific microbiome leading to mutually beneficial interactions between humans and their microbiome (Chiu et al. 2017). The lung microbiome, which is believed to be stable or at least transient in healthy people, is nowadays considered as a poly-microorganism component contributing to disease pathogenesis especially to chronic pulmonary diseases such as COPD, asthma and cystic fibrosis (CF). Most research studies on lung microbiome have focused on bacteria and their impact on lung health, but there is evidence that other nonbacterial organisms, constituting the virome or mycobiome, are playing an important physio-pathological role.

In the last few years, our research group focused on lung mycobiome analysis (Delhaes et al. 2018; Nguyen et al. 2016). Thanks to advances in culture independent methods especially deep sequencing, lung mycobiome appears to contribute to the decline of the lung function and the pulmonary disease progression in CF. By interacting with the bacteriome, it may act as a cofactor in inflammation and in the host immune response.

Project

Our major aim is to decipher the relationship between fungal and bacterial populations of lungs, inflammation, and other covariates such disease subtypes and indoor environment (exposome), by combining (i) mycobiome-microbiome analysis, (ii) computational inter-kingdom network analysis, (iii) ecological model investigation, and (iv) in-vitro experiments based on an ALI or bronchial epithelial, plus microbial coinfections of in-vitro cultures of cells.

Collectively, these approaches allowed us to propose a revised version of the CF lung model derived from ecology research field (Whiteson et al., 2014), and paves the way for future mechanistic studies on lung mycobiome, which should be successful in informing clinical decision-making. It also highlights the complexity of all respiratory microbiome components' connections, which might yield important insights within chronic pulmonary diseases.

 

The current objectives of the group are the following:

1) To assess lung mycobiome evolution during asthma and CF, especially during exacerbation

2) To decipher specific fungal factors that shape severe asthma, such as severe asthma with fungal sensitization and how fungal component will interact with microbial flora and/or host components

3) To investigate the clinical relevance of the “gut-lung axis” in chronic pulmonary diseases

4) To study the role of exogenous mycobiome (fungal exposome) in these pulmonary diseases

Main references

·         Delhaes L, Touati K, Faure-Cognet O, Cornet M, Botterel F, Dannaoui E, Morio F, Le Pape P, Grenouillet F, Favennec L, Le Gal S, Nevez G, Duhamel A, Borman A, Saegeman V, Lagrou K, Gomez E, Carro ML, Canton R, Campana S, Buzina W, Chen S, Meyer W, Roilides E, Simitsopoulou M, Manso E, Cariani L, Biffi A, Fiscarelli E, Ricciotti G, Pihet M, Bouchara JP. Prevalence, geographic risk factor, and development of a standardized protocol for fungal isolation in cystic fibrosis: Results from the international prospective study "MFIP". J Cyst Fibros. 2018 Oct 20. pii: S1569-1993(18)30839-7. doi: 10.1016/j.jcf.2018.10.001.

·         Chiu L, Bazin T, Truchetet ME, Schaeverbeke T, Delhaes L, Pradeu T. Protective Microbiota: From Localized to Long-Reaching Co-Immunity. Front Immunol. 2017 Dec 7;8:1678. doi: 10.3389/fimmu.2017.01678.

·         Nguyen LD, Deschaght P, Merlin S, Loywick A, Audebert C, Van Daele S, Viscogliosi E, Vaneechoutte M, Delhaes L. Effects of Propidium Monoazide (PMA) Treatment on Mycobiome and Bacteriome Analysis of Cystic Fibrosis Airways during Exacerbation. PLoS One. 2016 Dec 28;11(12):e0168860. doi: 10.1371/journal.pone.0168860.

·         Whiteson KL, Bailey B, Bergkessel M, Conrad D, Delhaes L, Felts B, Harris K, Hunter R, Lim YW, Maughan H, Quinn R, Salamon P, Sullivan J, Wagner BD, Rainey PB. The upper respiratory tract as a microbial source for pulmonary infections in cystic fibrosis. Parallels from island biogeography. Am J Respir Crit Care Med. 2014 Jun 1;189(11):1309-15. doi: 10.1164/rccm.201312-2129PP.

Bronchial Remodeling

Plateforme Technologique d'Innovation Biomédicale (PTIB)

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