PT  - JOURNAL ARTICLE
AU  - Hérivaux, Anaïs
AU  - Willis, Jesse R
AU  - Mercier, Toine
AU  - Lagrou, Katrien
AU  - Gonçalves, Samuel M
AU  - Gonçales, Relber A
AU  - Maertens, Johan
AU  - Carvalho, Agostinho
AU  - Gabaldón, Toni
AU  - Cunha, Cristina
TI  - Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
AID  - 10.1136/thoraxjnl-2020-216179
DP  - 2022 Mar 01
TA  - Thorax
PG  - 283--291
VI  - 77
IP  - 3
4099  - http://thorax.bmj.com/content/77/3/283.short
4100  - http://thorax.bmj.com/content/77/3/283.full
SO  - Thorax2022 Mar 01; 77
AB  - Rationale Recent studies have revealed that the lung microbiota of critically ill patients is altered and predicts clinical outcomes. The incidence of invasive fungal infections, namely, invasive pulmonary aspergillosis (IPA), in immunocompromised patients is increasing, but the clinical significance of variations in lung bacterial communities is unknown.Objectives To define the contribution of the lung microbiota to the development and course of IPA.Methods and measurements We performed an observational cohort study to characterise the lung microbiota in 104 immunocompromised patients using bacterial 16S ribosomal RNA gene sequencing on bronchoalveolar lavage samples sampled on clinical suspicion of infection. Associations between lung dysbiosis in IPA and pulmonary immunity were evaluated by quantifying alveolar cytokines and chemokines and immune cells. The contribution of microbial signatures to patient outcome was assessed by estimating overall survival.Main results Patients diagnosed with IPA displayed a decreased alpha diversity, driven by a markedly increased abundance of the Staphylococcus, Escherichia, Paraclostridium and Finegoldia genera and a decreased proportion of the Prevotella and Veillonella genera. The overall composition of the lung microbiome was influenced by the neutrophil counts and associated with differential levels of alveolar cytokines. Importantly, the degree of bacterial diversity at the onset of IPA predicted the survival of infected patients.Conclusions Our results reveal the lung microbiota as an understudied source of clinical variation in patients at risk of IPA and highlight its potential as a diagnostic and therapeutic target in the context of respiratory fungal diseases.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. The accession number for all sequencing data reported in this paper is NCBI Bioproject PRJNA647539.