The human gut harbors >100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Here, we review the quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis. Endotoxin derived from gut bacteria incites a powerful inflammatory response in the host organism. Furthermore, protein fermentation by gut microbiota generates myriad toxic metabolites, including p-cresol and indoxyl sulfate. Disruption of gut barrier function in CKD allows translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Several targeted interventions that aim to re-establish intestinal symbiosis, neutralize bacterial endotoxins, or adsorb gut-derived uremic toxins have been developed. Indeed, animal and human studies suggest that prebiotics and probiotics may have therapeutic roles in maintaining a metabolically-balanced gut microbiota and reducing progression of CKD and uremia-associated complications. We propose that further research should focus on using this highly efficient metabolic machinery to alleviate uremic symptoms.
Resident microbiota out number the human host cells by 10-fold, with metabolic activity in excess of that of the liver and a combined microbiome that is estimated to be 100 times greater than that of the human. In 2007, the Human Microbiome Project was established to characterize the human microbiome and analyze its role in health and disease. The project serves as a “roadmap” for discovering the roles these microorganisms play in human health and disease, with the goal of metagenomic characterization of microbial communities from 300 healthy individuals over time. Not long ago, the products of intestinal putrefaction were considered the primary uremic toxins. The recent explosion of knowledge on the metabolic potential of gut microbiome and its critical role in the pathogenesis of several chronic inflammatory diseases has led the nephrologist to refocus on the gut as a potential cause of CKD-related complication and a target organ for attenuating uremia-related complications. Therefore, it is time for more clinical and basic research studies to further our understanding of the role of the gut microbiome in progression of CKD and its associated complications. Finally, interventions aimed at establishing gut symbiosis and blocking microbiome-related pathogenic biochemical pathways should be explored in order to develop interventions to ameliorate uremic syndrome.