This is part one of a series of blogs discussing comprehensive gut restoration protocol and the progression of chronic kidney disease. Gut restoration and progression of CKD.
The Gut-Kidney Connection
Chronic kidney disease affects millions of American and is often associated with comorbid conditions such as cardiovascular disease, diabetes and hypertension. Dysbiosis and leaky gut are implicated in many systemic inflammatory and immune-related factors that lead to chronic disease. Dysbiosis is the term used to define alterations in the gut microbiota that includes overgrowth of bad bacteria, as well as underrepresentation of good bacteria. The normal integrity of the gut can be compromised resulting in systemic complaints, even in the absence of overt gut symptoms.
Gut Restoration and Progression of CKD
Research has established a relationship between gut microbes and different diseases, including kidney disease. This occurs through very complex biochemical and immune mechanisms. The presence of good bacteria has been associated with immune changes that inhibits inflammation. The use of probiotics and prebiotics that produce favorable changes in the microbiome have also been associated with gut changes that reduce advanced glycation end products (AGE), a uremic toxin associated with advancing kidney damage.
So, balancing the gut bacteria help slow kidney disease by directly inhibiting the immune response; and indirectly by reducing toxic burden known to progress CKD.
The Gut as a Potential Source of Inflammation
In the cases of dysbiosis, we see a rise in inflammatory markers that interact with the lining of the gut and result in damage and increased permeability or leaky gut. This causes shifts in the breakdown of nutrients, including amino acids. These shifts increase the levels of circulating substances involved in kidney disease and inflammation such as p-cresol, phenol, and indole. On top of that, these “pro-inflammatory” changes has also been associated with hypertension and increased risk of diabetes and cardiovascular disease; all of which are associated with CKD risk.
Yet, there have been inconsistencies in studies evaluating the benefits of targeting the gut-kidney axis with probiotics and prebiotics. Some suggest this may in part be due to the fact that research in this field is still in its infancy stage and conflicts in research may be due to statistical problems or inadequate interventions. But in an attempt to isolate the intervention, most studies utilized unilateral approach of inoculating the microbiome. In doing so, they usually fail to address other aspects of gut restoration and mucosal repair.
The Dysbiosis Cycle
In fact, changes in the gut bacteria do not operate as a one-way inflammatory force ending in damage to the lining of the gut. Instead it’s a dynamic process with a variety of contributing factors. Research confirms that it’s not only the dysbiosis that causes inflammatory damage, but also damage to the lining of the gut contributes to further dysbiosis and reduced production of short chain fatty acids (which feeds the lining of the gut). This, in-turn, increases the uremic waste products and further perpetuates growth of bad bacteria. This dysbiosis cycle damages the gut cell wall and promotes leakage of parts of the bad bacteria and toxins produced by these bacteria into the bloodstream. This leads to more inflammation, and the cycle repeats.
What is Missing in Current Research?
Individual Factors
As mentioned above, studies focusing on the use of probiotics to improve gut health and reduce inflammation and CKD risk have had mixed results. But these studies looked at a single change to see if it impacts kidney disease when in reality the process is more complex. Considerations for other factors that contribute to inflammation and CKD risk must also be accounted for. This includes environmental exposures, genetic risk factors, metabolic factors and changes in the body fluid volume that contribute to diabetes and hypertension, respectively, contributing to increased CKD risk.
Medications
On top of that, the effect of medication and polypharmacy on the gut and nutrient balance cannot be forgotten. Drugs commonly prescribed in kidney patients, like NSAIDs, Proton-pump inhibitors (PPI) or steroids, may also contribute to leaky gut. Changes in digestion due to some of these medications also contribute to altered nutrient absorption, including malabsorption of macronutrients, as well as micronutrients needed as cofactors in many biochemical reactions in the body.
Nutrients
The gut also can also serve as a source of increased oxidative stress, contributing to increased systemic inflammation that accelerates CKD and its comorbid conditions, including cardiovascular disease. Research suggests that one mechanism by which toxins generated by bacterial load speed up CKD progression is by altering metabolism and absorption of normally occurring nutrients. This may indicate that nutrient repletion maybe a necessary step for successful outcomes with probiotic re-inoculation.
The Bottom Line on Gut Restoration and Progression of CKD
This is why the use of an individualized comprehensive gut restoration protocol, that steps outside of the conventional linear model and takes into account the various layers described above can slow the progression of kidney disease. One such approach can be summarized by the 5R program which we will explain in details in the upcoming blogs.
