TY - JOUR
T1 - A High-Risk Profile for Invasive Fungal Infections Is Associated with Altered Nasal Microbiota and Niche Determinants
AU - Costantini, Claudio
AU - Nunzi, Emilia
AU - Spolzino, Angelica
AU - Merli, Francesco
AU - Facchini, Luca
AU - Spadea, Antonio
AU - Melillo, Lorella
AU - Codeluppi, Katia
AU - Marchesi, Francesco
AU - Marchesini, Gessica
AU - Valente, Daniela
AU - Dragonetti, Giulia
AU - Nadali, Gianpaolo
AU - Englmaier, Lukas
AU - Coufalikova, Katerina
AU - Spácil, Zdenek
AU - Bellet, Marina Maria
AU - Pariano, Marilena
AU - Renga, Giorgia
AU - Stincardini, Claudia
AU - D’Onofrio, Fiorella
AU - Bozza, Silvia
AU - Pagano, Livio
AU - Aversa, Franco
AU - Romani, Luigina
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Hematological malignancies
KW - Invasive fungal infection
KW - Kynurenine
KW - Nasal microbiome
KW - Tolerance
KW - Microbiota
KW - Bacteria
KW - Humans
KW - Nose
KW - Prospective Studies
KW - Invasive Fungal Infections
KW - Tryptophan
KW - Hematological malignancies
KW - Invasive fungal infection
KW - Kynurenine
KW - Nasal microbiome
KW - Tolerance
KW - Microbiota
KW - Bacteria
KW - Humans
KW - Nose
KW - Prospective Studies
KW - Invasive Fungal Infections
KW - Tryptophan
UR - http://hdl.handle.net/10807/223790
U2 - 10.1128/iai.00048-22
DO - 10.1128/iai.00048-22
M3 - Article
SN - 0019-9567
VL - 90
SP - 4822
EP - 4830
JO - Infection and Immunity
JF - Infection and Immunity
ER -