scholarly journals Nutritional Therapy Modulates Intestinal Microbiota and Reduces Serum Levels of Total and Free Indoxyl Sulfate and P-Cresyl Sulfate in Chronic Kidney Disease (Medika Study)

2019 ◽  
Vol 8 (9) ◽  
pp. 1424 ◽  
Author(s):  
Biagio Raffaele Di Iorio ◽  
Maria Teresa Rocchetti ◽  
Maria De Angelis ◽  
Carmela Cosola ◽  
Stefania Marzocco ◽  
...  

In chronic kidney disease (CKD), the gut-microbiota metabolites indoxyl sulfate (IS) and p-cresyl sulfate (PCS) progressively accumulate due to their high albumin-binding capacity, leading to clinical complications. In a prospective crossover controlled trial, 60 patients with CKD grades 3B–4 (GFR = 21.6 ± 13.2 mL/min) were randomly assigned to two dietary regimens: (i) 3 months of free diet (FD) (FD is the diet usually used by the patient before being enrolled in the Medika study), 6 months of very low protein diet (VLPD), 3 months of FD and 6 months of Mediterranean diet (MD); (ii) 3 months of FD, 6 months of MD, 3 months of FD, and 6 months of VLPD. VLPD reduced inflammatory Proteobacteria and increased Actinobacteria phyla. MD and VLPD increased some butyrate-forming species of Lachnospiraceae, Ruminococcaceae, Prevotellaceae, Bifidobacteriaceae, and decrease the pathobionts Enterobacteriaceae. The increased level of potential anti-inflammatory Blautia and Faecalibacterium, as well as butyrate-forming Coprococcus and Roseburia species in VLPD was positively associated with dietary intakes and it was negatively correlated with IS and PCS. Compared to FD and MD, VLPD showed a lower amount of some Lactobacillus, Akkermansia, Streptococcus, and Escherichia species. MD and VLPD reduced both the total and free serum IS (MD −36%, −40% and VLPD −69%, −73%, respectively) and PCS (MD −38%, −44% and VLPD −58%, −71%, respectively) compared to FD. VLPD reduced serum D-lactate compared to MD and FD. MD and, to a greater extent, VLPD are effective in the beneficial modulation of gut microbiota, reducing IS and PCS serum levels, and restoring intestinal permeability in CKD patients.

2021 ◽  
Vol 10 (4) ◽  
pp. 840
Author(s):  
Maria Teresa Rocchetti ◽  
Biagio Raffaele Di Iorio ◽  
Mirco Vacca ◽  
Carmela Cosola ◽  
Stefania Marzocco ◽  
...  

Nutritional therapy (NT) is a therapeutic option in the conservative treatment of chronic kidney disease (CKD) patients to delay the start of dialysis. The aim of this study was to evaluate the specific effect of ketoanalogs (KA)-supplemented diets for gut microbiota modulation. In a previous study we observed that the Mediterranean diet (MD) and a KA-supplemented very-low-protein diet (VLPD) modulated beneficially gut microbiota, reducing indoxyl- and p-cresyl-sulfate (IS, PCS) serum levels, and ameliorating the intestinal permeability in CKD patients. In the current study, we added a third diet regimen consisting of KA-supplemented MD. Forty-three patients with CKD grades 3B–4 continuing the crossover clinical trial were assigned to six months of KA-supplemented MD (MD + KA). Compared to MD, KA-supplementation in MD + KA determined (i) a decrease of Clostridiaceae, Methanobacteriaceae, Prevotellaceae, and Lactobacillaceae while Bacteroidaceae and Lachnospiraceae increased; (ii) a reduction of total and free IS and PCS compared to a free diet (FD)—more than the MD, but not as effectively as the VLPD. These results further clarify the driving role of urea levels in regulating gut integrity status and demonstrating that the reduction of azotemia produced by KA-supplemented VLPD was more effective than KA-supplemented MD in gut microbiota modulation mainly due to the effect of the drastic reduction of protein intake rather than the effect of KA.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 114
Author(s):  
Chih-Yu Yang ◽  
Ting-Wen Chen ◽  
Wan-Lun Lu ◽  
Shih-Shin Liang ◽  
Hsien-Da Huang ◽  
...  

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.


Author(s):  
Karla Thaís Resende Teixeira ◽  
Laís de Souza Gouveia Moreira ◽  
Natalia Alvarenga Borges ◽  
Isabela Brum ◽  
Bruna R. de Paiva ◽  
...  

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii253-iii253 ◽  
Author(s):  
Maria Teresa Rocchetti ◽  
Carmela Cosola ◽  
Ighli di Bari ◽  
Lucia Di Micco ◽  
Emanuele De Simone ◽  
...  

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 688
Author(s):  
Kullaya Takkavatakarn ◽  
Pongpratch Puapatanakul ◽  
Jeerath Phannajit ◽  
Warumphon Sukkumme ◽  
Pajaree Chariyavilaskul ◽  
...  

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups −5.61 mg/L; 95% CI −11.01 to −0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.


2018 ◽  
Vol 28 (3) ◽  
pp. 208-214 ◽  
Author(s):  
Ana Paula Black ◽  
Juliana S. Anjos ◽  
Ludmila Cardozo ◽  
Flávia L. Carmo ◽  
Carla J. Dolenga ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lixia He

Abstract Objectives Chronic kidney disease (CKD) is a global epidemic and posing serious health problems with an increasing prevalence worldwide. Effective preventive strategies are urgently needed. This study was conducted to investigate the effect of a fermented soybean product (ImmunBalance, IMB) and active lactic acid (ALA) on adenine-induced CKD in mice. Methods Female C57BL/6 mice were randomly assigned into one of the following experimental groups: negative control (NC), model control (MC), models with oral gavage of IMB at 250 (IMB-L) or 1000 mg/kg BW (IMB-H), ALA at 1000 (ALA-L) or 2000 mg/kg BW (ALA-H). The CKD model was established by ip. injection of adenine daily for 4 weeks, and treatments started the same day as adenine injection till for 8 weeks. The kidney histopathology was evaluated by H&E staining. Blood cytokines and kidney injury biomarkers were measured by Multiplex sandwich immunoassays. Expression of cytokines and stem cells-related genes in kidney was analyzed by quantitative real-time PCR. The levels of major phyla of gut microbiota were quantified by quantitative PCR. Results The CKD mice showed obvious tubular dilation, tubulointerstitium degeneration or atrophy, interstitial chronic and acute inflammation. The administration of IMB and ALA significantly improved histopathological damages. Both of IMB and ALA decreased serum levels of cytokines and kidney toxicity biomarkers MCP-1, IL-6, IP-10, TIMP-1, Cystatin C and Clusterin, and the mRNA levels of inflammatory biomarkers IL-6, IL-1β, TGF-β1, TLR-4, F4/80 and TNF-α in kidney samples. CKD increased gene expression levels of stem cell biomarkers in kidney, which were reduced by IMB or ALA treatment. CKD reduced gut Clostridium leptumb level that was significantly increased by IMB or ALA treatment. Conclusions Our results suggest that dietary supplementation of IMB or ALA may significantly delay the development and progression of CKD. Funding Sources Nichimo Biotics Co., Ltd and Lifetrade Co. Ltd, Japan.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Hafsatu Maiwada Suleiman ◽  
Mohammed Amina ◽  
Ibrahim Abubakar ◽  
Yusuf Rasheed ◽  
Mohammed Jibril El-Bashir ◽  
...  

The magnitude of chronic renal disease is enormous, as the prevalence of kidney failure is rising. Anaemia is a common complication of chronic kidney disease (CKD) that develops early in its course and becomes increasingly severe as the disease progresses. The aim is to evaluate the serum level of iron, Total Iron Binding Capacity (TIBC), transferrin saturation and ferritin in chronic kidney disease population in Zaria and control subjects. This study was conducted at ABUTH Zaria were 125 patients in various stages of CKD who presented at the nephrology clinic and equal number of apparently healthy age and sex matched controls were recruited. The mean (SD) age of patient and controls were 48 (14) years. These were made up of 53.6% males, and 46.4% females. Mean values of serum creatinine significantly higher in the patients (<0.0001). There was no significant difference in the mean values of iron (p=0.32) and TIBC (p=1.29) in both study groups. The patients had a significantly (p˂0.0001) higher mean value for ferritin and TSAT than the control group. There were higher serum creatinine and ferritin values in males than in females while higher serum TIBC, estimated creatinine clearance and iron were observed in females than males. Serum creatinine, ferritin and estimated creatinine clearance of male patients were found to be significantly higher with p-value of 0.002, 0.000 and 0.028 respectively than that of female patients. No significant differences were noted in serum levels of iron, TIBC and TSAT. Serum creatinine, ferritin and TSAT were found to be significantly elevated in CKD patients while serum Iron and TIBC were not.


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