|Year : 2020 | Volume
| Issue : 3 | Page : 70-73
Gut microbiota dysbiosis and chronic kidney disease
Brijesh Yadav1, Narayan Prasad2, Anita Saxena2
1 Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, Uttar Pradesh, India
2 Department of Nephrology and Renal Transplant, Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow, Uttar Pradesh, India
|Date of Submission||05-Oct-2020|
|Date of Acceptance||07-Nov-2020|
|Date of Web Publication||13-Apr-2021|
Dr. Brijesh Yadav
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
Chronic kidney disease (CKD) is an irreversible progressive health problem often associated with cardiovascular complication, bone mineral metabolism disorder, uremic toxin deposition, and immune dysregulation. The gut microbiome is an important modulator of immune function and performs a plethora of functions inside the host body. Several factors such as diet, antibiotic use, environmental pollutant modulates the composition of Gut microbiota. An intervention with dietary substances may be a therapeutic strategy to modulate the healthy Gut microbiota composition and slowing the progression of CKD.
Keywords: Chronic kidney disease, dysbiosis, gut microbiota, immune cell, short-chain fatty acids
|How to cite this article:|
Yadav B, Prasad N, Saxena A. Gut microbiota dysbiosis and chronic kidney disease. J Renal Nutr Metab 2020;6:70-3
|How to cite this URL:|
Yadav B, Prasad N, Saxena A. Gut microbiota dysbiosis and chronic kidney disease. J Renal Nutr Metab [serial online] 2020 [cited 2021 Jun 13];6:70-3. Available from: http://www.jrnm.in/text.asp?2020/6/3/70/313630
| Chronic Kidney Disease|| |
Chronic kidney disease (CKD) is an irreversible progressive problem associated with structural and functional damage in the kidney. It affects approximately 10%–13% of the world population and 17.2% of the Indian population and progress toward end-stage renal failure over the years. It is often associated with cardiovascular risk, dysregulated immune response, bone mineral metabolic disorder, accumulation of uremic toxin, and metabolites. Dysregulated inflammatory response often worsens the kidney function. Results of Vitamin-D supplementation and probiotics studies show positive impacts in inhibiting the progression of CKD, suggesting an intervention through dietary supplementation may be an effective strategy in the management of CKD patient,, Composition of diet impacts the quality of microbiota and overall health of the host. Recent study has shown a dysbiosis of Gut microbiota in CKD patients. However, it is the subject of debate, whether dysbiosis of Gut microbiota is the cause or effects of CKD. In this review, we will discuss Gut microbiota composition dysbiosis, function, and factors influencing in Gut microbiota composition and the mechanism how Gut microbiota may mediate CKD.
| Gut Microbiota|| |
The human gut microbiota comprises a complex niche of 100 trillion microbiota comprising a total of 1100 bacterial species of which at least 160 common bacterial species, which remained shared among the other members in the community, Gut microbiota mostly (90%) colonized in the distal gut. The total human microbiota counts is 10 times that of the total human cell and having a total gene 3.3 million genes, mostly of uncharacterized function.
An estimated total count of adult healthy human bacterial number is of the range 10^14, belongs to five major phyla, Firmicutes (80%), Bacteroidetes(20%), Actinobacteria(3%), Proteobacteria (1%), and Verrucomicrobia (0.1%) of total Gut microbiota, The Bacteroidetes (Gram-negative anaerobes), Firmicutes (Gram-positive anaerobes) are two predominating bacterial phyla in Gut, make approximately 90% of the total gut microbiota. The key member of phyla Firmicutes includes genera Roseburi, Clostridium, Eubacterium, Lactobacillus, Enterococcus, Ruminicoccus, Fecalibacterium. The member of phyla Bacteroidetes belongs to the family Bacteroidaceae, Prevotellaceae and Rikenellaceae, Xylanibacter. Low levels of Bifidobacteriaceae, Lactobacillaceae and higher levels of Enterobacteriaceae are associated with CKD.
| Gut Epithelial Integrity Barrier|| |
Gut intestinal epithelial cells (IECs) forms an intact continuous physical and biochemical barrier between gut lumen and inner mucosal tissues, requires for preventing the leakage of microbial components in blood stream. It is made of a single layer of columnar epithelial cells. Bifidobacterium of Phyla Actinobacteria is used as a major prebiotic in the treatment of many inflammatory diseases. Bifidobacterium increases the strength of intestinal integrity barrier by inducing increased ß-defensin-2, secretion and junctional protein ZO-1, Occludin and decreasing Claudin 2 synthesis in intestine epithelial cell.
| Gut Microbiota in Immune Cell Development|| |
Gut microbiota and the immune system have bidirectional relationship. Gut microbiota control immune cell development and later, immune cell regulate the colonization of specific set of microbiota,, Gut microbiota has microbial-associated molecular pattern, molecules such as flagellin, peptidoglycan, lipo-polysaccharides, teichoic acid, formyl peptides, polysaccharide-A (PSA), D-glycero-β-D-manno-heptose, that bind to pattern recognition receptors of the host (toll-like receptor 2 [TLR2], nod-like receptors, rig-1 like receptors) cell and prime immune cell for maturation and activation.
Studies have shown that Germfree mice had poor immune cell development and reduced number of CD4+ T, Th17 cell, reduced intraepithelial CD8+ T-cell and reduced secretory immunoglobulin-A and increased Th2 cell-specific signature molecule,,, Similarly, specific pathogen-free mice lead hyper-activation of B-cell activation factor (APRIL) together with increased hypogalctosylated IgA formation. Hypogalactosylated, antibody lead induction of immune response in many inflammatory diseases., The presence of capsular PSA of Bacteroides fragilis leads to Th1 cell development, and germfree mice lead to Th2 and B-cell development, Similarly, segmented filamentous bacteria, cytophaga-flavobacter-bacteroidetes and Helicobacter hepaticus induce Th17 development from naive CD4+ T cell,, suggesting a dysbiosis in a specific set of Gut microbiota might lead to an inflammatory immune response in CKD patients.
Gut microbiota plays an important role in orchestrating the immune function. Candida albicans colonization in the human gut leads to the secretion of pro-inflammatory cytokines interleukin (IL)-22 for the elimination of the Candida and other pathogens in the intestine. Members of Clostridium, and Akkermansia muciniphilla, Roseburi, Lactobacillus, Fecalibacterium facilitates degradation of dietary mucopolysaccharides and other dietary substances that generate short-chain fatty acids such as Butyrate, propionate, and Acetate, which induces anti-inflammatory Treg cell differentiation and proliferation from naïve CD4+ T cell and induces secretion of IL-10, IL-35 that inhibit inflammatory cell activation in colon and circulation. Member of the genus Clostridium and Fusobacterium are potent inducers of transforming growth factor (TGF)-ß1 from the IEC, which provides a milieu to differentiate intestinal naïve CD4+ T cell into T-regulatory cell,, Furthermore, Clostridium butyricum induces TLR2-dependent TGF-ß1 production from the lamina propria and Dendritic cell and facilitates induced Treg cell development in lamina propria which prevents Gut inflammation and leakage from gut into circulation.
| Microbiota Role in Vitamin Synthesis|| |
Vitamins works as co-enzymes for many enzymes required for the normal physiological homeostasis, like cellular metabolism and energy generation for cell division, blood clotting in host, signal transduction, etc., Inside the host, gut microbiota performs many vitamins synthesis from dietary substances, like folate, Biotin, Vitamin K, B12,. Lactobacillus spp. are found to be associated with Vitamin B12 production. Vitamins B12 is required for Red blood cells formation. A deficiency of B12 leads to diminish the immune function of CD8+ T and NK cell required for protection from pathogen infections. Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum produce folate, required for the blood cell formation a common problem in CKD patients.
| Gut Microbiota in Biotransformation|| |
Gut microbiota bio-transform environmental pollutant polycyclic aromatic hydrocarbon compounds into estrogenic intermediates, thus mediates secondary toxicity. Gut microbiota transform bile acid by deconjugation, dihydroxylation. An unconjugated and hydroxylated bile acid inhibit the efflux activity of the multidrug-resistant protein and permeable glycoprotein and increase the bio-availability of steroid medicine to the cell. Furthermore, microbiota ferments dietary protein and generates a myriad amount of uremic toxins like indoxyl sulfate, p-cresol, trimethyl-n-oxide, ammonia in the gut. Indoxyl-sulphate activates macrophage and induces inflammatory cytokines expression, while ammonia increases the gut permeability and allowing translocation of microbial components, food metabolite in circulation, aggravating the inflammation by activating the inflammatory cell,, Tri-methyl-n-oxide (TMAO) generated from the gut microbiota by fermenting meat and egg phosphocholine, and lecithin. TMAO is reported to be associated with cardiovascular risk; one of the common problems in CKD patients. Lactobacilli catabolize Tryptophan into indole-3-aldehyde (I3A), which binds to aryl-hydrocarbon receptors (AHR) on innate lymphoid cells-3, an inflammatory innate counterpart of Th17 cell. I3A mediates AHR signaling pathway-dependent secretion of cytokines, IL-22 from colon lymphocytes and increased expression of Gap junction protein, Claudin, Junctional adhesion molecules in the epithelial cell, these molecules are required for epithelial integrity barrier protection, thus reduces local and systemic inflammation.
| Factors Affecting Gut Microbiota|| |
Prebiotics are live microbial organisms given as a dietary supplement to boost the pre-existing microbiota in gut. Prebiotics work on gut microbiota, leading to the reduction of oxidative stress and inflammation in the gut cell, decreasing gut epithelial barrier permeability,, Further, they induce the increased secretion of IgA and anti-inflammatory cytokines from the mucosal plasma B-cell and helps in maintaining the intestinal permeability barrier and prevents translocation of microbial components from lumen to circulation.
Prebiotics are food substances that enhance the growth and activity of the intestinal gut microbiota like Bifidobacteria. They are nonabsorbable to the intestine, but their fermentation generates substances which are utilized by the colonocyte for their energy source. Common prebiotics is inulin-type fructans and short-chain fructooligosaccharides, found to be associated with decreased endotoxin and homeostasis model assessment.
Synbiotic is the combination of both prebiotics and probiotics. Synbiotics are used to promote bacterial growth and its functional activity, where either pro or prebiotics are not much effective alone. Synbiotics have shown an increased population of probiotics bacteria, Bifidobacteria and Lactobacillus.
Use of antibiotics
An intervention with antibiotics leads to gut microbiota dysbiosis and consequently aberrant immune cell development and leading to increase susceptibility to inflammatory diseases in CKD patients.,
It has been found that increasing environmental pollutant leads to gut microbiota dysbiosis in the general population., Carbon nanotube is found to be linked with increasing intestinal permeability, gut microbiota dysbiosis, and inflammatory gene expression in the intestine,, which may allow translocation of microbial components in circulation leading to systemic inflammatory effect.
| Conclusion|| |
Gut microbiota performs pleiotropic function inside the host cell, of which one of the important functions is the modulation of the immune system. A manipulation of Gut microbiota with dietary substances may be an effective strategy in reducing inflammation and slowing the progression of CKD in patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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