A High-Risk Profile for Invasive Fungal Infections Is Associated with Altered Nasal Microbiota and Niche Determinants

Claudio Costantini, Emilia Nunzi, Angelica Spolzino, Francesco Merli, Luca Facchini, Antonio Spadea, Lorella Melillo, Katia Codeluppi, Francesco Marchesi, Gessica Marchesini, Daniela Valente, Giulia Dragonetti, Gianpaolo Nadali, Lukas Englmaier, Katerina Coufalikova, Zdenek Spácil, Marina Maria Bellet, Marilena Pariano, Giorgia Renga, Claudia StincardiniFiorella D’Onofrio, Silvia Bozza, Livio Pagano, Franco Aversa, Luigina Romani

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

It is becoming increasingly clear that the communities of microorganisms that populate the surfaces exposed to the external environment, termed microbiota, are key players in the regulation of pathogen-host cross talk affecting the onset as well as the outcome of infectious diseases. We have performed a multicenter, prospective, observational study in which nasal and oropharyngeal swabs were collected for microbiota predicting the risk of invasive fungal infections (IFIs) in patients with hematological malignancies. Here, we demonstrate that the nasal and oropharyngeal microbiota are different, although similar characteristics differentiate high-risk from low-risk samples at both sites. Indeed, similar to previously published results on the oropharyngeal microbiota, high-risk samples in the nose were characterized by low diversity, a loss of beneficial bacteria, and an expansion of potentially pathogenic taxa, in the presence of reduced levels of tryptophan (Trp). At variance with oropharyngeal samples, however, low Trp levels were associated with defective host-derived kynurenine production, suggesting reduced tolerance mechanisms at the nasal mucosal surface. This was accompanied by reduced levels of the chemokine interleukin-8 (IL-8), likely associated with a reduced recruitment of neutrophils and impaired fungal clearance. Thus, the nasal and pharyngeal microbiomes of hematological patients provide complementary information that could improve predictive tools for the risk of IFI in hematological patients.
Lingua originaleEnglish
pagine (da-a)4822-4830
Numero di pagine9
RivistaInfection and Immunity
Volume90
DOI
Stato di pubblicazionePubblicato - 2022

Keywords

  • Hematological malignancies
  • Invasive fungal infection
  • Kynurenine
  • Nasal microbiome
  • Tolerance
  • Microbiota
  • Bacteria
  • Humans
  • Nose
  • Prospective Studies
  • Invasive Fungal Infections
  • Tryptophan

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