Pharyngeal microbial signatures are predictive of the risk of fungal pneumonia in hematologic patients

Claudio Costantini, Emilia Nunzi, Angelica Spolzino, Melissa Palmieri, Giorgia Renga, Teresa Zelante, Lukas Englmaier, Katerina Coufalikova, Zdenek Spácil, Monica Borghi, Marina M. Bellet, Enzo Acerbi, Matteo Puccetti, Stefano Giovagnoli, Roberta Spaccapelo, Vincenzo N. Talesa, Giuseppe Lomurno, Francesco Merli, Luca Facchini, Antonio SpadeaLorella Melillo, Katia Codeluppi, Francesco Marchesi, Gessica Marchesini, Daniela Valente, Giulia Dragonetti, Gianpaolo Nadali, Livio Pagano, Franco Aversa, Luigina Romani

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)e0010521-e0010538
Number of pages17
JournalInfection and Immunity
Volume89
DOIs
Publication statusPublished - 2021

Keywords

  • Airway microbiome
  • Animals
  • Antibiotics
  • Antifungal Agents
  • Disease Models, Animal
  • Hematologic Diseases
  • Hematologic Neoplasms
  • Hematological malignancies
  • Humans
  • Indole-3aldehyde
  • Invasive fungal infection
  • Metabolomics
  • Metagenome
  • Metagenomics
  • Mice
  • Microbiota
  • Mycoses
  • Pharynx
  • Pneumonia
  • Risk Assessment
  • Risk Factors
  • Tryptophan

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