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
doi: https://doi.org/10.1101/2023.05.25.542283

This article is a preprint and has not been certified by peer review.

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.