Introduction
Gut microbiota is essential in regulating nutrient metabolism and the formation of various metabolites that could affect the heart, kidney vascular system, and liver. It has a role in managing kidney health. The relationship between kidney disease and gut microbiota is bi-directional and termed the kidney-gut axis. This article reviews the role of gut microbiota in managing kidney health.
What Is Chronic Kidney Disease?
Chronic Kidney Disease (CKD) is a significant health concern affecting 13.4 percent of the population. Chronic kidney disease has a range of pathophysiologic processes, including kidney dysfunction or a decline in glomerular filtration rate. Diabetes and hypertension are predominant factors contributing to chronic kidney disease in adults, whereas kidney and urogenital tract anomalies at birth cause CKD in children. Currently, treatment with therapeutics targets factors that contribute to disease development. The therapeutics used are renin-angiotensin-aldosterone system inhibitors and drugs to control blood pressure and proteinuria (protein in urine).
Recent studies have demonstrated an association between chronic kidney disease and gut microbiota and metabolites.
What Is the Pathophysiology of Chronic Kidney Disease?
Chronic kidney disease development depends on the individual's age, presence of comorbidities, repeated acute kidney injury, and proteinuria level. Kidney function declining for more than three months is known as chronic. Most individuals with chronic kidney disease develop hyperfiltration, hypertrophy of nephrons (basic kidney unit), tubulointerstitial fibrosis, activation of the renin-angiotensin-aldosterone system, and disruption of endothelial barriers leading to reduced glomerular filtration rate and renal excretion efficacy.
The estimated glomerular filtration rate can determine the severity of chronic kidney disease. Individuals with severe CKD have a lower filtration rate. As the disease severity increases, the endocrine function of the kidney is lost.
What Is the Human Microbiome?
A human microbiome is a collection of all microbial DNA (deoxyribonucleic acid) within the body distributed in various body regions like the urinary tract, genital system, skin, respiratory tract, and oral cavity. Most of the microbiomes are present within the gut. These microbiomes aid in the digestive and metabolic process, vitamin production, stimulation of immune response, and protection against pathogens.
The human microbiome has a symbiotic (mutually beneficial) relationship in healthy individuals. However, chronic kidney disease alters human microbiomes, resulting in various diseases and pathological conditions.
What Are Gut Microbiomes?
The gut microbiome consists of thousands of microbial species. Gut microbiomes influence absorption, metabolism, and nutrient storage and profoundly affect host immunology. Additionally, gut microbiota influences the maintenance of the gut mucosal barrier, drug metabolism, immunomodulation (regulating the immune system), blood pressure, and protection against infections.
Gut microbiota differs among individuals and transforms during the human lifespan due to influences of factors like diet, medication, environment, and diseases. Lower microbiome diversity is reported in end-stage renal disease. Individuals with CKD had lower microbial flora of Bifidobacterium and Lactobacillus species.
Predominant gut bacteria in healthy individuals are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Internal and external stimuli can alter the gut bacteria. Alteration of gut bacteria could lead to severe CKD. Bifidobacterium and Lactobacilli prevent CKD progression and improve patient survival.
Dysbiosis of the gut plays a role in developing various inflammatory-related diseases. The altered microbiome could contribute to inflammation development in acute and chronic kidney disease. Dysbiosis of the gut increases intestinal mucosal barrier permeability, which releases pro-inflammatory mediators and endotoxins into the bloodstream, stimulating an inflammatory cascade.
Gut dysbiosis could also cause endothelial dysfunction and alter vasoconstrictor response, which results in hypertension. If the Lactobacillus count is low in the gut, the individual has a higher risk of developing hypertension and kidney disease.
What Is the Association Between Gut Microbiota and Chronic Kidney Disease?
Patients with chronic kidney disease have an altered gut microbiota, known as dysbiosis. The relationship between chronic kidney disease and gut microbiota is bi-directional; metabolites and toxins released by the gut could impact the progression of renal disease, and uremic concentration could affect the gut microbiota.
Chronic kidney disease is associated with enhanced intestinal permeability (leaky gut). Bacteria and lipopolysaccharides can translocate from the gut lumen to the bloodstream, stimulating immune cells and producing kidney inflammation. A leaky gut causes inflammation and malnutrition that accelerates chronic kidney disease progression.
Uremic toxins from individuals suffering from CKD can adversely affect gut microbiome growth. Individuals suffering from CKD have reduced Bifidobacterium and Lactobacillus species flora. CKD-related factors like low fiber intake, metabolic acidosis, malnutrition, antibiotics, or medications contribute to gut dysbiosis.
Harmful metabolites produced from the gut are trimethylamine N-oxide (TAMO), indoxyl sulfate, and p-cresyl sulfate. These metabolites could result in a declined estimated glomerular filtration rate, kidney interstitial fibrosis, endothelial dysfunction, and cardiovascular disorder. Accumulation of indoxyl sulfate and p-cresyl sulfate elevated morbidity and mortality risk. Serum levels of metabolites 5-methoxy tryptophan and indoxyl sulfate positively correlate with the progression of chronic kidney disease. When toxins metabolized from the gut accumulate, it causes loss of kidney function and increases mortality risk. However, specific metabolites like short-chain fatty acids and bile acids have renoprotective effects and help restore kidney function and improve patient survivability. Its role is to suppress the disruption to the epithelial barrier and regulate anti-inflammatory response.
Numerous uremic toxins and microbial metabolites accumulate in CKD patients' plasma, blood, stool, urine, and exhaled air.
How to Manage Gut Microbiota in Chronic Kidney Disease Patients?
Dietary interventions or prebiotics can alter the gut microbiota and improve clinical outcomes in chronic kidney disease patients by reducing uremic toxins. Prebiotics are non-digestible fibers in cereals, fruits, milk, honey, vegetables, and dietary supplements. It helps in increasing bacterial levels of Bifidobacterium and Lactobacillus. Increasing the microbiota of bacteria Bifidobacterium and Lactobacillus can suppress inflammation and improve renal function.
Consuming a diet rich in fiber and low in protein can help increase anti-inflammatory bacteria and produce short-chain fatty acids. A low-protein diet reduces the plasma concentration of indoxyl and p-cresyl sulfate. High-fiber diets enhance kidney function by lowering harmful uremic metabolites and reducing microbial diversity.
Consuming food rich in choline and L-claritin (precursors of TAMO) abundant in egg yolk, kidney, liver, milk, and meat could increase uremic toxin and reduce glomerular filtration rate and must be avoided.
Conclusion
Several studies support the association of microbial dysbiosis with renal diseases. There have also been changes to blood pressure in patients with gut dysbiosis. Additionally, various microbial metabolites tend to accumulate in the kidneys. Alterations to gut microbiota through dietary interventions and prebiotics can improve renal health.
