Intestinal microbiome and fitness in kidney disease
Environmental changes can induce diversity shifts within ecosystems that affect interactions between species. Similarly, the development of kidney disease induces shifts within the ecosystem of the intestinal microbiome, affecting host physiology and fitness. Renal failure itself, together with related changes in diet and medication, alters the microbiota and its secretome of micronutrients, nutrients and regulatory metabolites towards a phenotype characterized by the production of uraemic toxins, hence contributing to the clinical syndrome of uraemia and its complications. These alterations are associated with structural changes in the intestinal wall that impair barrier function and cause leakage of bacterial metabolites, bacterial wall products and live bacteria into the circulation. Thus, the intestinal microbiota represents a new therapeutic target to improve outcomes of chronic kidney disease (CKD) including symptoms of uraemia, metabolic changes, cardiovascular complications, aberrant immunity and disease progression. Initial interventional studies have shown promising effects of unselective probiotic preparations on kidney inflammation and uraemia in patients with CKD but longer term studies are needed. Here, we take an ecological approach to understand the role of the intestinal microbiota in determining survival fitness in kidney disease.The microbiome is increasingly recognized as an element that contributes to health and disease. Here, the authors take an ecological approach to describe the impact of factors related to chronic kidney disease on the fitness of different physiological systems and the effects of these changes on microbiota composition.Key pointsThe intestinal microbiota is a highly versatile ecosystem that contributes to host physiological processes, including intestinal barrier integrity, immunological fitness and metabolic fitness, and responds dynamically to intrinsic and extrinsic challenges.Crosstalk between the gut microbial ecosystem and human physiological systems is context dependent; nutrient intake and drug therapy are the most important exogenous modifiers of this crosstalk.CKD can induce changes in both the composition and metabolic activity of gut microbiota (dysbiosis) with consequences for various physiological processes.CKD and related changes in the microbiota impair intestinal barrier fitness and promote translocation of bacterial components into the circulation, which impairs immunological fitness by driving persistent systemic inflammation and immune paralysis.CKD and related changes in the microbiota also impair metabolic and cardiovascular fitness by secreting metabolites that favour insulin resistance, obesity, endothelial dysfunction and cardiovascular ageing.Faecal transplantation, specific microorganism targeted interventions or the use of prebiotics, probiotics or dietary interventions are potential strategies to correct or manipulate CKD related changes in the intestinal microbiota that contribute to uraemia, as well as the progression of CKD and CKD complications.
Nature Reviews Nephrology