| Autor: |
Patrick J. Dörner, Harithaa Anandakumar, Ivo Röwekamp, Facundo Fiocca Vernengo, Belén Millet Pascual-Leone, Marta Krzanowski, Josua Sellmaier, Ulrike Brüning, Raphaela Fritsche-Guenther, Lennart Pfannkuch, Florian Kurth, Miha Milek, Vanessa Igbokwe, Ulrike Löber, Birgitt Gutbier, Markus Holstein, Gitta Anne Heinz, Mir-Farzin Mashreghi, Leon N. Schulte, Ann-Brit Klatt, Sandra Caesar, Sandra-Maria Wienhold, Stefan Offermanns, Matthias Mack, Martin Witzenrath, Stefan Jordan, Dieter Beule, Jennifer A. Kirwan, Sofia K. Forslund, Nicola Wilck, Hendrik Bartolomaeus, Markus M. Heimesaat, Bastian Opitz |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-47149-z |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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