Doerner, Patrick J. and Anandakumar, Harithaa and Roewekamp, Ivo and Fiocca Vernengo, Facundo and Millet Pascual-Leone, Belen and Krzanowski, Marta and Sellmaier, Josua and Bruening, Ulrike and Fritsche-Guenther, Raphaela and Pfannkuch, Lennart and Kurth, Florian and Milek, Miha and Igbokwe, Vanessa and Loeber, Ulrike and Gutbier, Birgitt and Holstein, Markus and Heinz, Gitta Anne and Mashreghi, Mir-Farzin and Schulte, Leon N. and Klatt, Ann-Brit and Caesar, Sandra and Wienhold, Sandra-Maria and Offermanns, Stefan and Mack, Matthias and Witzenrath, Martin and Jordan, Stefan and Beule, Dieter and Kirwan, Jennifer A. and Forslund, Sofia K. and Wilck, Nicola and Bartolomaeus, Hendrik and Heimesaat, Markus M. and Opitz, Bastian (2024) Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung. NATURE COMMUNICATIONS, 15 (1): 2788. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)Abstract
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. Authors utilise a murine model of infection to provide mechanistic insight into how antimicrobial therapy may be a predisposing risk factor for hospital-acquired pneumonia. They show that antibiotic-induced microbiota perturbations compromise inflammatory monocytes and thereby impair antibacterial defence.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VENTILATOR-ASSOCIATED PNEUMONIA; GUT MICROBIOTA; DIETARY FIBER; FETAL MONOCYTES; INFECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Aug 2025 08:23 |
| Last Modified: | 21 Aug 2025 08:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65500 |
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