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The Gut-Kidney Axis?!

Recent research has uncovered a link between the composition and function of the gut microbiome and risk of chronic kidney disease (CKD) (Cosola et al., 2018).

CKD is the presence of impaired kidney function for over 3 months and is characterised by a loss of function by the tiny filtering units in the kidneys called nephrons. This condition effects 1 in 10 Australians, with Indigenous Australians, the elderly and those with lower socioeconomic status at higher risk. Diabetes, hypertension, kidney infection and certain autoimmune diseases are all known causes for CKD. (AIHW, 2022)


Diet plays a key role in determining risk of chronic kidney disease (CKD). Part of this risk is due to the role of diet in diabetes and hypertension onset, but part of this risk is also mediated by the gut microbiome!

Fibre and compounds including curcumin (found in turmeric) appear to play a key role in reducing CKD risk by acting on the gut. Over 70% of our immune system resides in the gut, which makes the microbiome an important factor in determining how our immune system acts i.e. whether it promotes pro or anti-inflammatory pathways. Pro-inflammatory signals from the gut increase risk of chronic disease including CKD. Increased gut permeability (known as "leaky gut") may also increase risk of CKD by promoting inflammation.

Certain gut conditions including constipation are also strongly correlated with the onset and progression of CKD! (Cosola et al., 2018)

Causative factors for CKD such as high blood pressure and diabetes are influenced by the gut microbiome (Hills et al., 2019).

High blood pressure increases work for the kidneys and can damage parts of their intricate structure (the tiny nephrons)! The oral microbiome plays a very important role in controlling our blood pressure. The tiny microbes in our mouths help to convert dietary nitrates into nitric oxide which is essential for the widening of blood vessels resulting in a reduction in blood pressure. (Rosier et al., 2020)

To read more about this check out my previous blog post (https://www.gut-logic.com/post/the-oral-microbiome).

Diabetes risk is influenced by the gut microbiome through a number of pathways. Different compositions of microbes are known to increase the extraction of calories from our food, to increase the blood sugar response to our food and to increase inflammation which can contribute to the onset or progression of insulin resistance. The compound butyrate which is produced in large amounts by a healthy microbiome and a higher fibre diet is known to benefit energy metabolism and reduce risk of cardiometabolic conditions. (Hills et al., 2019).

A gut microbiome which predominantly breaks down fibre and creates beneficial metabolites like butyrate is called a saccharolytic microbiome - meaning it breaks down polysaccharides (carbohydrates). A saccharolytic microbiome is protective in CKD versus a proteolytic microbiome (a microbiome which primarily breaks down protein). The by-products of proteolytic reactions include pro-inflammatory compounds like hydrogen sulphide, secondary bile acids, and other phenols and indoles which are key uremic toxins found in CKD patients. (Montemurno et al., 2014)

Not only does the microbiome effect CKD risk/outcomes, but CKD itself effects the gut microbiome. When nephrons within the kidneys begin to fail during the course of CKD, the gut is used to compensate for this lack of function. The colons role as an excretion system is upregulated to take up the slack. This means the colon deals with the removal of urea, uric acid and oxalates from the body, a job ordinarily performed mostly by the kidneys. This excretion through the colon significantly changes the composition of the colonic microbiome. (Montemurno et al., 2014)

High levels of urine in the blood (uremia) seen in CKD also effects the gut by increasing intestinal permeability (“leaky gut”). This allows the escape of inflammatory compounds like lipopolysaccharide (LPS) which activates an inflammatory immune response. This creates a viscious cycle with CKD dysrupting the gut microbiome which then releases more LPS which progresses kidney damage (Montemurno et al., 2014). But, we may be able to interrupt this cycle by providing fibre, prebiotics, probiotics and nutrients which protect the gut barrier and reduce levels of LPS!


Key take aways:

  • Eat your fibre!

  • A healthy gut microbiome can lower systemic inflammation reducing your risk of chronic disease including chronic kidney disease.

  • Chronic kidney disease can negativey effect the gut microbiome.

  • Research suggests a diet high in fibre and polyphenols may even help reduce risk of kidney diseases strongly influenced by genetics including polycystic kidney disease (PKD) (Cosola et al., 2018).

References:


Australian Institute of Health and Welfare (AIHW). (2022).

Chronic kidney disease Overview - Australian Institute of Health and Welfare (aihw.gov.au)


Cosola, C., Sabatino, A., di Bari, I., Fiaccadori, E., Gesualdo, L. (2018). Nutrients, nutraceuticals, and

xenobiotics affecting renal health. Nutrients, 10(7), 808. https://doi.org/10.3390/nu10070808


Hills, R. D., Pontefract, B. A., Mishcon, H. R., Black, C. A., Sutton, S. C., & Theberge, C. R. (2019). Gut microbiome: Profound implications for diet and disease. Nutrients, 11(7). https://doi.org/10.3390/nu11071613

Montemurno, E., Cosola, C., Dalfino, G., Daidone, G., De Angelis, M,. Gobbetti, M & Gesualdo, L.

(2014). What would you like to eat, Mr CKD microbiota? A Mediterranean diet please! Kidney Blood Press Res, 2014(39). https://doi.org/10.1159/000355785


Rosier, B. T., Buetas, E., Moya-Gonzalvez, E. M., Artacho, A., & Mira, A. (2020). Nitrate as a potential prebiotic for the oral microbiome. Scientific Reports, 10(1), 12895. https://doi.org/10.1038/s41598-020-69931-x



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