Microbiome analysis of uremic mice

Infections are the second major cause of mortality in patients with kidney disease and accompanying uremia. Both vascular access and non-access related infections contribute equally to the infection-related deaths in patients with kidney disease. The dialysis procedure is the most common source of systemic infection by Candida albicans in these patients. C. albicans also reside in the gastro-intestinal tract as an opportunistic commensal fungus. However, the contribution of gut-derived C. albicans in non-access related infections in kidney disease is unknown. Using a mouse model of kidney disease, we demonstrate that uremic animals showed increased gut barrier permeability, impaired mucosal defense and dysbiosis. The disturbance in gut homeostasis is sufficient to drive the translocation of gut microbiota and intestinal pathogen Citrobacter rodentium to extra-intestinal sites but not C. albicans. Interestingly, uremic animals showed fungal translocation and systemic infection when gut epithelial barrier integrity is disrupted. Our data demonstrate that uremia coupled with gut mucosal damage aid in the translocation of commensal Candida albicans and cause fatal systemic infection in kidney disease. Since majority of the individuals with kidney disease suffer from some form of mucosal damage, these results have important implications in the prevention and control of non-access related infections in these patients