Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 Mar 2024
30 Mar 2024
Historique:
received:
17
05
2023
accepted:
20
03
2024
medline:
31
3
2024
pubmed:
31
3
2024
entrez:
30
3
2024
Statut:
epublish
Résumé
Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP.
Identifiants
pubmed: 38555356
doi: 10.1038/s41467-024-47149-z
pii: 10.1038/s41467-024-47149-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2788Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : OP 86/12-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : OP 86/13-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB-TR84 A5
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 1449 B02
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB-TR84 A5
Informations de copyright
© 2024. The Author(s).
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