Uremia is an illness that accompanies kidney failure and chronic kidney disease (CKD). Uremic illness is considered to be due largely to the accumulation of organic waste products that are normally cleared by the kidneys. However, uremic retention solutes are generated in part in the gastrointestinal tract (GIT), with the gut microbiota and the ensuing micro-biometabolome playing a significant role in the proliferation of uremic retention solutes. Toxins generated in, or introduced into the body via the intestine, such as advanced glycation end products, phenols, and indoles, all may contribute to the pathogenesis of CKD. Hence, it is biologically plausible, but not well recognized, that an important participant in the toxic load that contributes to CKD originates in the GIT. The microbiota that colonize the GIT perform a number of functions that include regulating the normal development and function of the mucosal barriers; assisting with maturation of immunological tissues, which in turn promotes immunological tolerance to antigens from foods, the environment, or potentially pathogenic organisms; controlling nutrient uptake and metabolism; and preventing propagation of pathogenic micro-organisms. Here, we develop a hypothesis that probiotics and prebiotics have a therapeutic role in maintaining a metabolically balanced GIT, and reducing progression of CKD and associated uremia.