Kidney-Gut Axis in Chronic Kidney Disease: Therapeutic Perspectives from Microbiota Modulation and Nutrition

Abstract

Chronic kidney disease (CKD) has a high prevalence worldwide, with an increasing incidence. One of the mechanisms of CKD progression involves a disordered inter-organ relationship between the kidneys and the intestine, known as the kidney-gut axis. In CKD, two pathological gut conditions-disturbed gut microbiota composition called uremic dysbiosis and leaky gut-contribute to the progression of CKD. Dysbiosis is associated with the increased production of gut-derived uremic toxins, leaky gut, and chronic systemic inflammation, leading to worsening uremia, which in turn aggravates the gut condition. This vicious cycle should be a target of the therapeutic strategy against CKD. The modulation of uremic dysbiosis, including prebiotics, probiotics, and synbiotics, has been a typical treatment approach, although clinical evidence for their efficacy has been insufficient. Some non-antibiotic drugs have an impact on human gut bacteria that are believed to play a role in their clinical efficacy on kidney function. Nutrition therapies, including a low-protein diet, dietary fiber, a Mediterranean diet, and whole grains, positively influence gut microbiota composition and have been linked to a decreased risk of CKD. Novel strategies are currently being explored, involving the use of postbiotics, microbiome sequencing techniques, and fecal microbiota transplantation, although clinical application remains to be tested. Human trials investigating the above-mentioned interventions remain inconclusive due to several limitations, including dietary variability and genetic factors. Future research should focus on the development of more effective probiotics, prebiotics, and microbial metabolism-modifying drugs, not only for CKD but for other systemic diseases as well.

Keywords: chronic kidney disease; diet; intervention; kidney-gut axis; microbiota.

Figure 1

Kidney-gut axis.

Figure 2

Gut-derived uremic toxins–gut microbiota metabolites. BMT: betaine methyltransferase.

Figure 3

Changes in the intestinal environment in renal failure. IL-6; interleukin-6. Modified Ref. [2]. Thin arrows mean molecular changes or causal link. Thick arrows mean the increase or the decrease in molecules or microbiota.