scholarly journals The Association between Gut Microbiota and Uremia of Chronic Kidney Disease

2020 ◽  
Vol 8 (6) ◽  
pp. 907 ◽  
Author(s):  
Ji Eun Kim ◽  
Hyo-Eun Kim ◽  
Ji In Park ◽  
Hyunjeong Cho ◽  
Min-Jung Kwak ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Kidney Function ◽  
Kidney Diseases ◽  
Toxin Production ◽  
Positive Interactions ◽  
Uremic Toxin ◽  
Serum Concentrations ◽  
Pyruvate Metabolism

Chronic kidney disease (CKD)-associated uremia aggravates—and is aggravated by—gut dysbiosis. However, the correlation between CKD severity and gut microbiota and/or their uremic metabolites is unclear. We enrolled 103 CKD patients with stage 1 to 5 and 46 healthy controls. We analyzed patients’ gut microbiota by MiSeq system and measured the serum concentrations of four uremic metabolites (p-cresyl sulfate, indoxyl sulfate, p-cresyl glucuronide, and trimethylamine N-oxide) by liquid chromatography–tandem mass spectrometry. Serum concentrations of the uremic metabolites increased with kidney function deterioration. Gut microbial diversity did not differ among the examined patient and control groups. In moderate or higher stage CKD groups, Oscillibacter showed positive interactions with other microbiota, and the proportions of Oscillibacter were positively correlated with those of the uremic metabolites. The gut microbiota, particularly Oscillibacter, was predicted to contribute to pyruvate metabolism which increased with CKD progression. Relative abundance of Oscillibacter was significantly associated with both serum uremic metabolite levels and kidney function. Predicted functional analysis suggested that kidney-function-associated changes in the contribution of Oscillibacter to pyruvate metabolism in CKD may greatly affect the gut environment according to kidney function, resulting in dysbiosis concomitant with uremic toxin production. The gut microbiota could be associated with uremia progression in CKD. These results may provide basis for further metagenomics analysis of kidney diseases.

scholarly journals Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression

Toxins ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 300 ◽  
Author(s):  
Esmeralda Castillo-Rodriguez ◽  
Raul Fernandez-Prado ◽  
Raquel Esteras ◽  
Maria Perez-Gomez ◽  
Carolina Gracia-Iguacel ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Toxin Production ◽  
Uremic Toxins ◽  
Uremic Toxin ◽  
Ckd Progression ◽  
Increased Risk

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl sulphate, indoxyl sulphate and indole-3 acetic acid. Increased intake of some nutrients may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of CKD progression. This offers the opportunity for therapeutic intervention by either modifying the diet, modifying the microbiota, decreasing uremic toxin production by microbiota, increasing toxin excretion or targeting specific uremic toxins. We now review the link between nutrients, microbiota and uremic toxin with CKD progression. Specific focus will be placed on the generation specific uremic toxins with nephrotoxic potential, the decreased availability of bacteria-derived metabolites with nephroprotective potential, such as vitamin K and butyrate and the cellular and molecular mechanisms linking these toxins and protective factors to kidney diseases. This information provides a conceptual framework that allows the development of novel therapeutic approaches.

scholarly journals Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 114
Author(s):  
Chih-Yu Yang ◽  
Ting-Wen Chen ◽  
Wan-Lun Lu ◽  
Shih-Shin Liang ◽  
Hsien-Da Huang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Statistical Significance ◽  
Additional Treatment ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Healthy Controls ◽  
Gut Dysbiosis ◽  
Novel Concept

Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology. Of note, indoxyl sulfate is a gut microbe-derived uremic toxin that accumulates in CKD patients. Nevertheless, the relationship between gut microbiota, fecal indole content, and blood indoxyl sulfate level remains unknown. In our study, we established an adenine-induced CKD rat model, which recapitulates human CKD-related gut dysbiosis. Synbiotic treatment in CKD rats showed a significant reduction in both the indole-producing bacterium Clostridium and fecal indole amount. Furthermore, gut microbiota diversity was reduced in CKD rats but was restored after synbiotic treatment. Intriguingly, in our end-stage kidney disease (ESKD) patients, the abundance of indole-producing bacteria, Bacteroides, Prevotella, and Clostridium, is similar to that of healthy controls. Consistently, the fecal indole tends to be higher in the ESKD patients, but the difference did not achieve statistical significance. However, the blood level of indoxyl sulfate was significantly higher than that of healthy controls, implicating that under an equivalent indole production rate, the impaired renal excretion contributes to the accumulation of this notorious uremic toxin. On the other hand, we did identify two short-chain fatty acid-producing bacteria, Faecalibacterium and Roseburia, were reduced in ESKD patients as compared to the healthy controls. This may contribute to gut dysbiosis. We also identified that three genera Fusobacterium, Shewanella, and Erwinia, in the ESKD patients but not in the healthy controls. Building up gut symbiosis to treat CKD is a novel concept, but once proved effective, it will provide an additional treatment strategy for CKD patients.

Dietary Changes Involving Bifidobacterium longum and Other Nutrients Delays Chronic Kidney Disease Progression

2018 ◽  
Vol 47 (5) ◽  
pp. 325-332 ◽  
Author(s):  
Yuko Iwashita ◽  
Masaki Ohya ◽  
Mitsuru Yashiro ◽  
Tomohiro Sonou ◽  
Kazuki Kawakami ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Kidney Function ◽  
Sham Group ◽  
Control Diet ◽  
Bifidobacterium Longum ◽  
Inorganic Phosphorus ◽  
Mineral And Bone Disorder ◽  
Serious Adverse Events

Background: Recent studies suggest that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment. However, the gut microbiota and kidney disease interactions remain to be determined. This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease (CKD). As uremic toxins are associated with CKD-related mineral and bone disorder, the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism (SHPT). Methods: 5/6 nephrectomy (Nx) rats were developed as the CKD model. Sham-operated (sham) rats were used as the control. To investigate the effectiveness of prebiotics (glutamine, dietary fiber, and oligosaccharide) and probiotics (Bifidobacterium longum strain; GFOB diet), rats were randomly assigned to 4 groups: Nx group fed the GFOB diet (n = 10); Nx group fed the control (CON) diet (n = 10); sham group fed the GFOB diet (n = 5); and sham group fed the control diet (n = 5). Blood, feces, and kidney samples were collected and analyzed. Results: Serum creatinine (Cre) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group. Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group, and significantly correlated with serum Cre. Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group. Conclusion: Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events.

scholarly journals Maternal Adenine-Induced Chronic Kidney Disease Programs Hypertension in Adult Male Rat Offspring: Implications of Nitric Oxide and Gut Microbiome Derived Metabolites

2020 ◽  
Vol 21 (19) ◽  
pp. 7237 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Hung-Wei Yang ◽  
Chih-Yao Hou ◽  
Guo-Ping Chang-Chien ◽  
Sufan Lin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Adult Male ◽  
Male Offspring ◽  
Uremic Toxin ◽  
Microbiota Composition ◽  
Adverse Pregnancy ◽  
Gut Microbiota Composition

Maternal chronic kidney disease (CKD) during pregnancy causes adverse fetal programming. Nitric oxide (NO) deficiency, gut microbiota dysbiosis, and dysregulated renin-angiotensin system (RAS) during pregnancy are linked to the development of hypertension in adult offspring. We examined whether maternal adenine-induced CKD can program hypertension and kidney disease in adult male offspring. We also aimed to identify potential mechanisms, including alterations of gut microbiota composition, increased trimethylamine-N-oxide (TMAO), reduced NO bioavailability, and dysregulation of the RAS. To construct a maternal CKD model, female Sprague-Dawley rats received regular chow (control group) or chow supplemented with 0.5% adenine (CKD group) for 3 weeks before pregnancy. Mother rats were sacrificed on gestational day 21 to analyze placentas and fetuses. Male offspring (n = 8/group) were sacrificed at 12 weeks of age. Adenine-fed rats developed renal dysfunction, glomerular and tubulointerstitial damage, hypertension, placental abnormalities, and reduced fetal weights. Additionally, maternal adenine-induced CKD caused hypertension and renal hypertrophy in adult male offspring. These adverse pregnancy and offspring outcomes are associated with alterations of gut microbiota composition, increased uremic toxin asymmetric and symmetric dimethylarginine (ADMA and SDMA), increased microbiota-derived uremic toxin TMAO, reduced microbiota-derived metabolite acetate and butyrate levels, and dysregulation of the intrarenal RAS. Our results indicated that adenine-induced maternal CKD could be an appropriate model for studying uremia-related adverse pregnancy and offspring outcomes. Targeting NO pathway, microbiota metabolite TMAO, and the RAS might be potential therapeutic strategies to improve maternal CKD-induced adverse pregnancy and offspring outcomes.

scholarly journals Dietary Phosphorus Differentially Alters Uremic Toxin Production in a Rat Model of Chronic Kidney Disease

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 843-843
Author(s):  
Dennis Cladis ◽  
Kendal Schmitz ◽  
Amber Jannasch ◽  
Bruce Cooper ◽  
Kathleen Hill Gallant
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Rat Model ◽  
Kidney Tissue ◽  
Toxin Production ◽  
Sham Operation ◽  
Uremic Toxin ◽  
Sprague Dawley ◽  
Waste Products ◽  
Dietary Phosphorus

Abstract Objectives Chronic kidney disease (CKD) is characterized by declining kidney function, limiting the kidney's ability to efficiently remove metabolic waste products from circulation. Byproducts of gut microbial protein metabolism, termed uremic retention solutes (URS), accumulate in CKD patients and are associated with accelerating kidney decline. The gut microbes responsible for generating URS are dependent upon phosphorus (P) for growth and survival. As dietary P restriction is a cornerstone of CKD treatment, we hypothesized that changes in dietary P loads would alter URS production. Methods To evaluate this, 8-week-old male Sprague Dawley rats underwent 5/6th nephrectomy (Nx, n = 24) or sham operation (n = 20) and were maintained on a 0.6% P diet (w/w) for three weeks. Animals were then randomized to receive either low (0.1% (w/w)) or high (1.2% (w/w)) P diets for 4h/d for 7d. Blood was collected at the start and end of the 7d diet (baseline and sacrifice, respectively). Serum was analyzed for blood urea nitrogen (BUN) and URS, including trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS), via LC-MS. Results Nx rats had significantly elevated BUN compared to sham controls (38.9 ± 5.9 vs 23.1 ± 5.1 mg/dL, p < 0.0001). Additionally, the presence of significantly enlarged kidney tissue in Nx animals verified the progression of kidney decline. At sacrifice, all URS were elevated in Nx animals as compared to sham controls (p < 0.0001), though changes in dietary P loads only affected IS production (low vs. high, p = 0.0003). When comparing baseline to sacrifice, TMAO decreased, IS remained consistent, and pCS increased in all rats. Conclusions Our results indicate that dietary P loads may differentially affect the production of some URS in a rat model of CKD. As dietary P restriction is one of the cornerstones of CKD treatment, we posit that this dietary strategy influences URS production, CKD progression, and, ultimately, health outcomes. Funding Sources ASBMR, NIH K01.

scholarly journals Butyrate producing microbiota are reduced in chronic kidney diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bei Gao ◽  
Adarsh Jose ◽  
Norma Alonzo-Palma ◽  
Taimur Malik ◽  
Divya Shankaranarayanan ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Disease Severity ◽  
Kidney Diseases ◽  
Health Concern ◽  
Chronic Kidney Diseases ◽  
Component Systems ◽  
Advanced Stages ◽  
Two Component Systems

AbstractChronic kidney disease is a major public health concern that affects millions of people globally. Alterations in gut microbiota composition have been observed in patients with chronic kidney disease. Nevertheless, the correlation between the gut microbiota and disease severity has not been investigated. In this study, we performed shot-gun metagenomics sequencing and identified several taxonomic and functional signatures associated with disease severity in patients with chronic kidney disease. We noted that 19 microbial genera were significantly associated with the severity of chronic kidney disease. The butyrate-producing bacteria were reduced in patients with advanced stages of chronic kidney diseases. In addition, functional metagenomics showed that two-component systems, metabolic activity and regulation of co-factor were significantly associated with the disease severity. Our study provides valuable information for the development of microbiota-oriented therapeutic strategies for chronic kidney disease.

scholarly journals Fiber intake and health in people with chronic kidney disease

2021 ◽  
Author(s):  
Guobin Su ◽  
Xindong Qin ◽  
Changyuan Yang ◽  
Alice Sabatino ◽  
Jaimon T Kelly ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Dietary Fiber ◽  
Patient Adherence ◽  
Toxin Production ◽  
Current Evidence ◽  
Future Research ◽  
Uremic Toxin ◽  
Fiber Intake ◽  
Adequate Diet

Abstract Emerging evidence suggests that diet, particularly one that is rich in dietary fiber, may prevent the progression of chronic kidney disease (CKD) and its associated complications in people with established CKD. This narrative review summarizes the current evidence and discusses the opportunities for increasing fiber intake in people with CKD to improve health and disease complications. A higher consumption of fiber exerts multiple health benefits, such as increasing stool output, promoting the growth of beneficial microbiota, improving the gut barrier and decreasing inflammation, as well decreasing uremic toxin production. Despite this, the majority of people with CKD consume less than recommended dietary fiber intake, which is part may be due to the competing dietary potassium concern. Based on existing evidence, we see benefits from adopting a higher intake of fiber-rich food, and recommend cooperation with the dietitian to ensure an adequate diet plan. We also identify knowledge gaps for future research and suggest means to improve patient adherence to a high-fiber diet.

Uremic Toxin-Producing Gut Microbiota in Rats with Chronic Kidney Disease

Nephron ◽  
2016 ◽  
Vol 135 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Mami Kikuchi ◽  
Mariko Ueno ◽  
Yoshiharu Itoh ◽  
Wataru Suda ◽  
Masahira Hattori
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Uremic Toxin

scholarly journals Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients

2020 ◽  
Vol 21 (6) ◽  
pp. 1986 ◽  
Author(s):  
Tessa Gryp ◽  
Geert R.B. Huys ◽  
Marie Joossens ◽  
Wim Van Biesen ◽  
Griet Glorieux ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Bacterial Species ◽  
Uremic Toxins ◽  
Bacterial Number ◽  
Uremic Toxin ◽  
Microbial Composition ◽  
Indolic Compounds ◽  
Cardiovascular Morbidity And Mortality

In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid, originate from phenolic and indolic compounds, which are end products of gut bacterial metabolization of aromatic amino acids (AAA). This study investigates gut microbial composition at different CKD stages by isolating, identifying and quantifying PBUT precursor-generating bacteria. Fecal DNA extracts from 14 controls and 138 CKD patients were used to quantify total bacterial number and 11 bacterial taxa with qPCR. Moreover, isolated bacteria from CKD 1 and CKD 5 fecal samples were cultured in broth medium supplemented with AAA under aerobic and anaerobic conditions, and classified as PBUT precursor-generators based on their generation capacity of phenolic and indolic compounds, measured with U(H)PLC. In total, 148 different fecal bacterial species were isolated, of which 92 were PBUT precursor-generators. These bacterial species can be a potential target for reducing PBUT plasma levels in CKD. qPCR indicated lower abundance of short chain fatty acid-generating bacteria, Bifidobacterium spp. and Streptococcus spp., and higher Enterobacteriaceae and E. coli with impaired kidney function, confirming an altered gut microbial composition in CKD.

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