Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients

Abstract

RationaleRecent 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.ObjectivesTo define the contribution of the lung microbiota to the development and course of IPA.Methods and measurementsWe 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 resultsPatients 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.ConclusionsOur 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.

Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus on Aspergillus spp.

“…Although a link between the lung bacterial microbiota composition and the disease outcome in patients with invasive pulmonary aspergillosis has been recently demonstrated ( 200 ), many knowledge gaps still exist regarding the link between the pulmonary microbiota and Aspergillus spp. infections.…”

Lung and gut microbiomes in pulmonary aspergillosis: Exploring adjunctive therapies to combat the disease

“…Rhamnolipids inhibit the growth of A. fumigatus in in vitro experiments (37) (Figure 1, Table 1). Moreover, Heŕivaux et al (20) observed a loss of bacterial diversity and overgrowth of bacteria (e.g., Staphylococcus, Escherichia, Paraclostridium, and Finegoldia genera) in the lungs of patients with IPA. These changes in the lung microbiome were predictive of disease outcomes across IPA.…”

“…On the other hand, human complications are often accompanied by microbiome alterations, and as such, determination of the microbiome signature could potentially offer a robust diagnostic tool, and its leverage could subsequently aid in timely and effective treatment. For instance, Heŕivaux et al (20) reported that microbiome diversity was found to predict IPA onset and the mortality rate associated with this complication. Apart from scattered studies reported thus far, the association of the human microbiome with PA remains largely elusive.…”

Effects of Helicobacter pylori Infection on the Oral Microbiota of Reflux Esophagitis Patients

“…Smoking increases nitrate intake, and Veillonella converts nitrate into carcinogenic nitrosamines and pro-inflammatory nitric oxide (Jia et al, 2021). Vanhatalo's studies reported that Prevotella and Veillonella are positively correlated and are essential markers of early inflammation, leading to an increase in the number of lymphocytes and centrioles (Heŕivaux et al, 2021;Vanhatalo et al, 2021). Several recent studies have shown that lactic acid and glucose are metabolized into short-chain fatty acids by Veillonella, which promotes mucin synthesis (Chen et al, 2020).…”