Klebsiella oxytoca facilitates microbiome recovery via antibiotic degradation and restores colonization resistance in a diet-dependent manner

Éva d. H. Almási, Lea Eisenhard, Lisa Osbelt, Till Robin Lesker, Anna C. Vetter, Nele Knischewski, Agata Anna Bielecka, Achim Gronow, Uthayakumar Muthukumarasamy, Marie Wende, Caroline Tawk, Meina Neumann-Schaal, Mark Brönstrup and Till Strowig ()
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Éva d. H. Almási: Helmholtz Centre for Infection Research (HZI)
Lea Eisenhard: Helmholtz Centre for Infection Research (HZI)
Lisa Osbelt: Helmholtz Centre for Infection Research (HZI)
Till Robin Lesker: Helmholtz Centre for Infection Research (HZI)
Anna C. Vetter: Helmholtz Centre for Infection Research (HZI)
Nele Knischewski: Helmholtz Centre for Infection Research (HZI)
Agata Anna Bielecka: Helmholtz Centre for Infection Research (HZI)
Achim Gronow: Helmholtz Centre for Infection Research (HZI)
Uthayakumar Muthukumarasamy: Helmholtz Centre for Infection Research (HZI)
Marie Wende: Helmholtz Centre for Infection Research (HZI)
Caroline Tawk: Helmholtz Centre for Infection Research (HZI)
Meina Neumann-Schaal: Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures
Mark Brönstrup: Helmholtz Centre for Infection Research (HZI)
Till Strowig: Helmholtz Centre for Infection Research (HZI)

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Competition among bacteria for carbohydrates is pivotal for colonization resistance (CR). However, the impact of Western-style diets on CR remains unclear. Here we show how the competition between Klebsiella oxytoca and Klebsiella pneumoniae is modulated by consuming one of three Western-style diets characterized by high-starch, high-sucrose, or high-fat/high-sucrose content. In vivo competition experiments in ampicillin-treated mice reveal that K. oxytoca promotes K. pneumoniae decolonization on all dietary backgrounds. However, mice on the high-fat/high-sucrose diet show reduced pathogen clearance. Microbiome analysis reveals that the combination of Western-style diets and ampicillin treatment synergize in microbiome impairment, particularly noticeable in the presence of high dietary fat content. The diet-independent degradation of ampicillin in the gut lumen by K. oxytoca beta-lactamases facilitates rapid commensal outgrowth, which is required for subsequent pathogen clearance. Our findings provide insights into how diet modulates functional microbiome recovery and K. oxytoca-mediated pathogen elimination from the gut.

Date: 2025
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DOI: 10.1038/s41467-024-55800-y

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