Lung infections play a critical role in cystic fibrosis (CF) pathogenesis. CF respiratory tract is now considered to be a polymicrobial niche and advances in high-throughput sequencing allowed to analyze its microbiota and mycobiota. However, no NGS studies until now have characterized both communities during CF pulmonary exacerbation (CFPE). Thirty-three sputa isolated from patients with and without CFPE were used for metagenomic high-throughput sequencing targeting 16S and ITS2 regions of bacterial and fungal rRNA. We built inter-kingdom network and adapted Phy-Lasso method to highlight correlations in compositional data. The decline in respiratory function was associated with a decrease in bacterial diversity. The inter-kingdom network revealed three main clusters organized around Aspergillus, Candida, and Scedosporium genera. Using Phy-Lasso method, we identified Aspergillus and Malassezia as relevantly associated with CFPE, and Scedosporium plus Pseudomonas with a decline in lung function. We corroborated in vitro the cross-domain interactions between Aspergillus and Streptococcus predicted by the correlation network. For the first time, we included documented mycobiome data into a version of the ecological Climax/Attack model that opens new lines of thoughts about the physiopathology of CF lung disease and future perspectives to improve its therapeutic management. Lung infections play a critical role in cystic fibrosis (CF) pathogenesis where they can lead to significant acute decrease of lung function, known as CF pulmonary exacerbation (CFPE). Developments of next-generation sequencing (NGS) approaches allowed us to understand microbiome composition that can contribute to lung physiopathology in both healthy individuals and patients with lung disease. More recently, NGS together with advances into statistical network inference tools allowed to analyze the microbial airway communities, appreciate the inter-kingdom equilibrium of respiratory floras, and therefore develop understanding of microbial communities as a whole 1-7. Acute CFPEs represent major clinical events that significantly decline the lung function, contribute to disease progression and require adapted, prompt anti-infectious treatment 8-11. Omics approaches confirmed associations between bacterial community and exacerbation 12-20. Apart from bacteria that are well known agents causing dramatic recurrent CFPEs, respiratory viruses have been recently found to be associated with CFPE, independently

In recent years, the gut microbiota has been considered as a full-fledged actor of the gut–brain axis, making it possible to take a new step in understanding the pathophysiology of both neurological and psychiatric diseases. However, most of the studies have been devoted to gut bacterial microbiota, forgetting the non-negligible fungal flora. In this review, we expose how the role of the fungal component in the microbiota-gut-brain axis is legitimate, through its interactions with both the host, especially with the immune system, and the gut bacteria. We also discuss published data that already attest to a role of the mycobiome in the microbiota-gut-brain axis, and the impact of fungi on clinical and therapeutic research.

Background The links between microbial environmental exposures and asthma are well documented, but no study has combined deep-sequencing results from pulmonary and indoor microbiomes of asthmatic patients with spirometry, clinical and endotype parameters. Objective The goal of this study was to investigate the links between indoor microbial exposures and pulmonary microbial communities and to document the role of microbial exposures on inflammatory and clinical outcomes of patients with severe asthma (SA). Methods Fifty-five SA patients from the national COBRA cohort were enrolled for analyzing their indoor microbial flora through the use of electrostatic dust collectors (EDCs). Among these patients, 22 were able to produce sputa during stable or pulmonary exacerbation periods and had complete pairs of EDC and sputum samples, both collected and analysed. We used amplicon targeted metagenomics to compare microbial communities from EDC and sputum samples of patients according to type 2 (T2)-asthma endotypes. Results Compared to patients with T2-low SA, patients with T2-high SA exhibited an increase in bacterial alpha-diversity and a decrease in fungal alpha-diversity of their indoor microbial floras, the latter being significantly correlated with FeNO levels. The beta-diversity of the EDC mycobiome significantly clustered according to T2 endotypes. Moreover, the proportion of fungal taxa in common between sputum and EDC samples was significantly higher when patients exhibited acute exacerbation. Conclusion These results illustrated, for the first time, a potential association between the indoor mycobiome and clinical features of SA patients, which should renew interest in deciphering the interactions between indoor environment, fungi, and host in asthma.