The gut microbiota is the diverse community of microorganisms that reside within the gastrointestinal tract. The importance of the composition (what types of microorganisms), function (what they are doing), and the metabolites (what are they producing) has been highlighted in health and disease. In the case of chronic kidney disease (CKD), it is of great interest as the gut microbiota has been linked to the disease itself and the progression of kidney dysfunction.
The gut microbiota in chronic kidney disease
In CKD there are changes at the level of composition and function (e.g., enzymatic capacity) and metabolites produced by gut microbes. These changes have been assessed by examining mostly stool samples through experimental models (e.g., mouse or rat models of kidney disease by removing a large portion of the kidneys (5/6th) or by providing a toxic agent in the diet (i.e., adenine)) or in individuals with CKD not yet on dialysis and those undergoing dialysis treatment.
The changes in composition of the gut microbiota include having less bacterial species richness (amount of diversity within a sample) and an increased abundance of bacteria that are considered pathogenic or “bad”, while there is a reduction in the abundance of bacteria that are traditionally considered symbiotic or “good”. With these changes, the gut microbiota of CKD patients is considered dysbiotic or out of balance.
At the functional level, it has been reported that the fecal samples from individuals undergoing dialysis have an increased amount of enzymes that produce toxins that are increased as kidney function declines, mostly those that produce protein degradation metabolites (i.e., urea, uric acid, tyrosine, and tryptophan). Also, there is a decrease in the enzymes needed for the production of short-chain fatty acids, which are mostly produced from the fermentation of dietary fiber and thus are traditionally considered “good”.
At the metabolite level, mirroring the effect on the enzymes needed for the production of toxins derived from amino acid and protein degradation, metabolites such as indoles and phenols derived exclusively from the gut microbes are increased in the plasma of CKD patients.
Therapies that target the composition, function, and metabolites produced are of great interest in the CKD community
Due to the changes mentioned above, therapies that target the composition of the gut microbiota, the function of the gut microbiota, and what the gut microbes are producing are of great interest to try to reduce the burden of CKD. These therapies may include the use of pro-, pre-, and synbiotics.
The use of probiotics in CKD is not supported by the current evidence
Probiotics are live microorganisms that when consumed in specific amounts may give the individual a benefit. There are several probiotic bacteria, including species and strains within the Bifidobacterium and Lactobacillus families. Probiotic bacteria have been studied extensively in healthy individuals and those with several diseases. Some of the benefits in patients with CKD may include binding to pathogenic bacteria, decreased levels of inflammation, reduction of toxins produced by the microbes, and improvement of the health of the gastrointestinal tract.
Although the possible beneficial effects of supplementation with probiotics sounds promising, the current evidence does not support their use. In a recent meta-analysis by McFarlane and collaborators, they found no benefit of the use of probiotics on the levels of serum urea, indoles, and phenols. In fact, when you go to the individual studies, some of them found increases in these toxins and markers of inflammation, while they report no changes in the composition of the gut microbiota.
The use of prebiotics may have a beneficial effect in CKD
Prebiotics are substrates (including dietary fibers that are fermented by the microbes) that are used by the gut microbes producing short-chain fatty acids to provide a benefit to the host. While probiotics have not been associated with beneficial effects, the use of prebiotics may provide a better solution in patients with CKD.
The use of prebiotic substances in CKD has been limited to the use of prebiotic fibers, such as resistant starch, oligofructose-enriched inulin, and arabinoxylans, among others. In the meta-analysis by McFarlane and collaborators, they found that the use of prebiotics reduced levels of serum urea. However, there was no effect on other metabolites produced by gut microbes or the composition of the gut microbiota.
Not pro- or prebiotics, but what about synbiotics?
Synbiotics are the combination of pro- and prebiotics. While the use of pro- or prebiotics on their own have not yielded the expected results, the use of synbiotics seems promising.
Rossi and collaborators examined the effect of a synbiotic in patients with CKD not yet on dialysis. The synbiotic contained 15g of a combination of prebiotic fibers and a probiotic with nine strains from the Lactobacillus, Bifidobacteria, and Streptococcus genera. They found decreases in serum indoxyl sulfate (derived from the fermentation of the amino acid tryptophan) and changes in the composition of the gut microbiota.
Viramontes-Hörner and collaborators found that the use of a probiotic gel with 2.3g of prebiotic fiber, a probiotic with Lactobacillus and Bifidobacterium, omega-3 fatty acids and vitamins decreased the severity of gastrointestinal symptoms, a highly prevalent problem in patients with CKD.
So, should we recommend the use of pro-, pre-, and synbiotics in patients with CKD?
Although the fundamental idea makes sense, the use of these interventions targeting the gut microbiota has not produced the expected results. However, CKD is a complex disease and individuals with reduced kidney function are often recommended a restrictive diet low in dietary fiber and a variety of medications with unknown effects on the gut microbiome. This may be the reason why some of these interventions may not be enough to cause a change in the gut microbiome. Hopefully, future interventions will apply a more holistic approach to assess and target the gut microbiome in patients with CKD.