Intestinal Colonization and Disseminated Infection of Klebsiella pneumoniae is Dependent on Dietary Carbohydrates

Bacterial translocation from the gut microbiota is a source of sepsis in critically ill and immunosuppressed patients. Previous work suggests that overgrowth of gut pathobionts in the family of bacteria Enterobacteriaceae, including Klebsiella pneumoniae, increases the risk of disseminated infection. Our data from a human dietary intervention study found that in the absence of fiber, K. pneumoniae bloomed during microbiota recovery from antibiotic treatment. We thus hypothesized that dietary nutrients directly support or suppress colonization of this gut pathobiont in the microbiota. Consistent with our human subject study, complex carbohydrates in dietary fiber suppressed colonization of K. pneumoniae and allowed for recovery of competing commensals in the native microbiota in mouse modeling. By contrast, through ex-vivo and in vivo modeling, we identify simple carbohydrates as a limiting resource for K. pneumoniae in the gut. As proof of principle, supplementation with lactulose, a non-absorbed simple carbohydrate and an FDA approved therapy, increased colonization of K. pneumoniae. Disruption of the intestinal epithelium led to dissemination of K. pneumoniae into the bloodstream and liver, which was prevented by dietary fiber. Our results show that dietary simple and complex carbohydrates are critical not only in the regulation of pathobiont colonization but also in disseminated infection, suggesting that targeted dietary interventions may offer a therapeutic strategy in susceptible patients.