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[Preprint]. 2023 Jun 11:2023.05.25.542283. Originally published 2023 May 25. [Version 2] doi: 10.1101/2023.05.25.542283

Colonization and Dissemination of Klebsiella pneumoniae is Dependent on Dietary Carbohydrates

Aaron L Hecht, Lisa C Harling, Elliot S Friedman, Ceylan Tanes, Junhee Lee, Jenni Firrman, Vincent Tu, LinShu Liu, Kyle Bittinger, Mark Goulian, Gary D Wu
PMCID: PMC10245944  PMID: 37292978

Abstract

Dysbiosis of the gut microbiota is increasingly appreciated as both a consequence and precipitant of human disease. The outgrowth of the bacterial family Enterobacteriaceae is a common feature of dysbiosis, including the human pathogen Klebsiella pneumoniae . Dietary interventions have proven efficacious in the resolution of dysbiosis, though the specific dietary components involved remain poorly defined. Based on a previous human diet study, we hypothesized that dietary nutrients serve as a key resource for the growth of bacteria found in dysbiosis. Through human sample testing, and ex-vivo , and in vivo modeling, we find that nitrogen is not a limiting resource for the growth of Enterobacteriaceae in the gut, contrary to previous studies. Instead, we identify dietary simple carbohydrates as critical in colonization of K. pneumoniae . We additionally find that dietary fiber is necessary for colonization resistance against K. pneumoniae , mediated by recovery of the commensal microbiota, and protecting the host against dissemination from the gut microbiota during colitis. Targeted dietary therapies based on these findings may offer a therapeutic strategy in susceptible patients with dysbiosis.

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