Kidney–Gut axis: study shows potential link between gut dysbiosis and chronic kidney disease

In a recent article published in Nutrients, researchers reviewed published scientific work on the kidney-gut axis, defined as the bidirectional relationship between gut microbiota and chronic kidney disease (CKD), the impact of the microbiome dysbiosis on CKD and the current pharmacological and non-pharmacological therapeutic options for CKD treatment. 

Background

The human gut microbiota, comprised of trillions of diverse microbial entities, is a complex ecosystem carrying out essential life functions, e.g., digestion, nutrient synthesis, and immune system development.

Its composition and function are diverse, and each individual has a highly personal gut microbiota depending on dietary habits, genetics, and environmental factors. In infants, the gut microbiome is constantly under transformation; thus, it is particularly prone to disruptions.

The gut microbiome dysbiosis often compromises the integrity of the intestinal barrier, which, in turn, causes the translocation of bacteria and the buildup of toxic metabolites, including urea, p-cresyl sulfate (PCS), and indoxyl sulfate (IS). 

These inflammation-mediated aberrant metabolic processes trigger the overproduction of antibodies, immune complexes, and inflammatory factors, which directly/indirectly damage the renal parenchyma.

Thus, understanding the complex interplay of the human gut microbiota with external factors is a rapidly evolving area of research with significant implications for health and disease.

It could help scientists develop effective interventions, such as microbial therapies, to promote a healthy gut. When administered at an early age, these interventions could mitigate the risk of developing several diseases in the future and promote overall health.

The kidney–gut axis in CKD

The concept of Developmental Origins of Health and Disease (DOHaD) suggests that poor maternal nutrition or exposure to toxins during prenatal development cause early disruptions to an infant’s gut microbiota.

Such infants are born with a low number of nephrons, a condition referred to as low nephron endowment, which makes them prone to developing CKD and hypertension in later life. Early interventions and preventive strategies are, thus, crucial for normal kidney development.

The researchers described the adverse effects of nitric oxide (NO) deficiency in early life. NO plays many crucial roles in the body, such as the modulation of sodium transporters to regulate blood pressure. Emerging evidence suggests a potential link between insufficient NO and a dysregulated renin-angiotensin system in secondary hypertension among CKD patients. In addition, uremic toxins disrupt the epithelial tight junction and weaken the antioxidative system of the human body. It likely explains why CKD patients have lower levels of antioxidant enzymes, e.g., Cu-Zn superoxide dismutase.

Furthermore, gut microbiota dysbiosis in adults with CKD could disrupt short-chain fatty acids (SCFAs), resulting in inflammation and impaired immune function. Given the negative impact of uremic toxins on the growth of good intestinal microbes, CKD patients tend to have lower levels of Bifidobacterium and Lactobacillus species. 

Research also suggests that excessive antibiotic use and malnutrition could severely harm the uremic environment, such that CKD could turn into end-stage renal disease. However, data on the role of the kidney–gut axis in pediatric renal diseases is scarce.

Doctors commonly prescribe antibiotic therapy in neonatal and pediatric populations, which disrupts their intestinal microbiota. It enriches the reservoir of antibiotic-resistance genes, which get transferred to pathogens and make them antibiotic-resistant.

As is well-recognized, the development of antibiotic resistance makes it challenging to treat infections, especially in patients with recurrent urinary tract infections (UTIs).

Frequent reliance on antibiotic therapy also affects the urobiome. Accordingly, studies have associated the absence of microbes capable of breaking down oxalate, e.g., Oxalobacter formigenes, with the formation of kidney stones.

Thus, therapies that modulate the gut microbiota have been implemented in clinical practice to treat kidney diseases, including CKD. These involve dietary interventions, pre-, pro-, and postbiotics, fecal microbiota transplantation (FMT), and phytotherapy.

They use several natural compounds, especially polyphenols, in phytotherapy to treat antibiotic-resistant bacterial infections. Cranberry (Vaccinium macrocarpon), a distinct source of flavonoids and phenolic acids, could prevent bacterial colonization in UTIs.

Another therapeutic approach to restoring gut microbiome diversity in adults and children is FMT. However, data on the use of FMT in CKD and other kidney diseases among children is scarce.

Conclusion

Overall, the current study highlighted many relevant findings from published literature exploring the association between gut microbial dysbiosis and CKD.

These findings suggested a link between loss of gut microbiome diversity and microbiota-derived metabolites, like butyrate-producing bacteria and SCFA, and kidney diseases; however, this was mainly in the adult population.

Thus, there is a need for more large-scale studies focused on the pediatric population to establish a definitive association between gut microbiota and pediatric renal diseases.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.