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Pharyngeal Microbial Signatures Are Predictive of the Risk of Fungal Pneumonia in Hematologic Patients
Claudio Costantini1, Emilia Nunzi1,2, Angelica Spolzino3
1Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Abstract:
The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airway dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that were associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes, such as Clostridiales and Bacteroidetes, along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients and indicates avenues for antimicrobial stewardship and metabolic reequilibrium in IFI.
Insights
Airway dysbiosis, specifically reduced microbial diversity in the pharynx, increases the risk of invasive fungal infections (IFI) in patients with hematological malignancies. This is linked to a loss of beneficial bacteria and altered tryptophan metabolism.
Area of Science:
- Microbiology
- Hematology
- Immunology
Background:
- Predicting invasive fungal infections (IFI) is crucial for treating hematological malignancy patients.
- Gut dysbiosis is recognized in these patients, but the role of airway dysbiosis in IFI risk is unknown.
Purpose of the Study:
- To investigate the association between airway dysbiosis and the risk of developing IFI in patients with hematological malignancies.
Main Methods:
- Prospective, observational study of 173 hematological malignancy patients.
- Functional microbiota characterization using nasal and oropharyngeal swabs.
- Stratification based on IFI risk and analysis of microbial richness, evenness, taxonomy, and metabolism.
Main Results:
- High-risk IFI patients exhibited lower pharyngeal microbial richness and evenness.
- Distinct taxonomic and metabolic profiles were observed in high-risk patients' pharyngeal microbiota.
- A murine model demonstrated that loss of anaerobes (e.g., Clostridiales, Bacteroidetes) and reduced tryptophan availability are linked to IFI risk.
Conclusions:
- Airway dysbiosis, particularly in the pharynx, is a significant risk factor for IFI in hematological patients.
- Microbial and metabolic alterations, including reduced protective anaerobes and tryptophan availability, contribute to IFI pathogenesis.
- Findings suggest potential for antimicrobial stewardship and metabolic interventions to prevent IFI.
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