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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 2/2019

01-02-2019 | Original Article

Effects of Probiotics on Inflammation and Uremic Toxins Among Patients on Dialysis: A Systematic Review and Meta-Analysis

Authors: Charat Thongprayoon, Wisit Kaewput, Spencer T. Hatch, Tarun Bathini, Konika Sharma, Karn Wijarnpreecha, Patompong Ungprasert, Matthew D’Costa, Michael A. Mao, Wisit Cheungpasitporn

Published in: Digestive Diseases and Sciences | Issue 2/2019

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Abstract

Background/Objectives

We performed this systematic review and meta-analysis to evaluate effects of probiotics on inflammation, uremic toxins, and gastrointestinal (GI) symptoms in end-stage renal disease (ESRD) patients.

Methods

A literature search was conducted utilizing MEDLINE, EMBASE, and Cochrane Database from inception through October 2017. We included studies that assessed assessing effects of probiotics on inflammatory markers, protein-bound uremic toxins (PBUTs), and GI symptoms in ESRD patients on dialysis. Effect estimates from the individual study were extracted and combined utilizing random effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO; No. CRD42017082137.

Results

Seven clinical trials with 178 ESRD patients were enrolled. There was a significant reduction in serum C-reactive protein (CRP) from baseline to post-probiotic course (≥ 2 months after treatment) with standardized mean difference (SMD) of − 0.42 (95% CI − 0.68 to − 0.16, p = 0.002). When compared to control, patients who received probiotics also had a significant higher degree of reduction in CRP level with SMDs of − 0.37 (95% CI − 0.72 to 0.03, p = 0.04). However, there were no significant changes in serum TNF-alpha or albumin with SMDs of − 0.32 (95% CI − 0.92 to 0.28, p = 0.29) and 0.16 (95% CI − 0.20 to 0.53, p = 0.39), respectively. After probiotic course, there were also significant decrease in PBUTs and improvement in overall GI symptoms (reduction in GI symptom scores) with SMDs of − 0.61 (95% CI − 1.16 to − 0.07, p = 0.03) and − 1.04 (95% CI − 1.70 to − 0.38, p = 0.002), respectively.

Conclusion

Our study demonstrates potential beneficial effects of probiotics on inflammation, uremic toxins, and GI Symptoms in ESRD patients. Future large-scale clinical studies are required to assess its benefits on other important clinical outcomes including patient mortality.
Appendix
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Literature
1.
2.
American Diabetes Association. Older adults. Sec. 11. In standards of medical care in diabetes-2017. Diabetes Care. 2017;40:S99–S104.CrossRef
3.
4.
Anderson S, Halter JB, Hazzard WR, et al. Prediction, progression, and outcomes of chronic kidney disease in older adults. J Am Soc Nephrol. 2009;20:1199–1209.CrossRefPubMed
5.
Sanguankeo A, Upala S, Cheungpasitporn W, Ungprasert P, Knight EL. Effects of statins on renal outcome in chronic kidney disease patients: a systematic review and meta-analysis. PLoS One. 2015;10:e0132970.CrossRefPubMedPubMedCentral
6.
Nissenson AR. Improving outcomes for ESRD patients: shifting the quality paradigm. Clin J Am Soc Nephrol. 2014;9:430–434.CrossRefPubMed
7.
8.
Kahrstrom CT, Pariente N, Weiss U. Intestinal microbiota in health and disease. Nature. 2016;535:47.CrossRefPubMed
9.
Di Iorio BR, Marzocco S, Nardone L, et al. Urea and impairment of the gut-kidney axis in chronic kidney disease. G Ital Nefrol. 2017;34:19.
10.
Firouzi S, Haghighatdoost F. The effects of prebiotic, probiotic, and synbiotic supplementation on blood parameters of renal function: a systematic review and meta-analysis of clinical trials. Nutrition. 2018;51–52:104–113.CrossRefPubMed
11.
Rossi M, Johnson DW, Campbell KL. The kidney-gut axis: implications for nutrition care. J Ren Nutr. 2015;25:399–403.CrossRefPubMed
12.
Rossi M, Johnson DW, Morrison M, et al. SYNbiotics easing renal failure by improving gut microbiology (SYNERGY): a protocol of placebo-controlled randomised cross-over trial. BMC Nephrol. 2014;15:106.CrossRefPubMedPubMedCentral
13.
Rossi M, Johnson DW, Morrison M, et al. Synbiotics easing renal failure by improving gut microbiology (SYNERGY): a randomized trial. Clin J Am Soc Nephrol. 2016;11:223–231.CrossRefPubMedPubMedCentral
14.
15.
Iwashita Y, Ohya M, Yashiro M, et al. Dietary changes involving bifidobacterium longum and other nutrients delays chronic kidney disease progression. Am J Nephrol. 2018;47:325–332.CrossRefPubMed
16.
17.
Lau WL, Savoj J, Nakata MB, Vaziri ND. Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins. Clin Sci (Lond). 2018;132:509–522.CrossRef
18.
Antza C, Stabouli S, Kotsis V. Gut microbiota in kidney disease and hypertension. Pharmacol Res. 2018;130:198–203.CrossRefPubMed
19.
Neto MPC, Aquino JS, da Silva LFR, et al. Gut microbiota and probiotics intervention: a potential therapeutic target for management of cardiometabolic disorders and chronic kidney disease? Pharmacol Res. 2018;130:152–163.CrossRef
20.
21.
22.
Vaziri ND. CKD impairs barrier function and alters microbial flora of the intestine: a major link to inflammation and uremic toxicity. Curr Opin Nephrol Hypertens. 2012;21:587–592.CrossRefPubMedPubMedCentral
23.
Vaziri ND. Effect of synbiotic therapy on gut-derived uremic toxins and the intestinal microbiome in patients with CKD. Clin J Am Soc Nephrol. 2016;11:199–201.CrossRefPubMedPubMedCentral
24.
Emal D, Rampanelli E, Stroo I, et al. Depletion of gut microbiota protects against renal ischemia-reperfusion injury. J Am Soc Nephrol. 2017;28:1450–1461.CrossRefPubMed
25.
Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol. 2014;25:657–670.CrossRefPubMed
26.
Noel S, Martina-Lingua MN, Bandapalle S, et al. Intestinal microbiota-kidney cross talk in acute kidney injury and chronic kidney disease. Nephron Clin Pract. 2014;127:139–143.CrossRefPubMed
27.
Schwenger EM, Tejani AM, Loewen PS. Probiotics for preventing urinary tract infections in adults and children. Cochrane Database Syst Rev. 2015;12:CD008772.
28.
Kirk J, Dunker KS. Dietary counseling: the ingredient for successfully addressing the use of herbal supplements and probiotics in chronic kidney disease. Adv Chronic Kidney Dis. 2014;21:377–384.CrossRefPubMed
29.
Abratt VR, Reid SJ. Oxalate-degrading bacteria of the human gut as probiotics in the management of kidney stone disease. Adv Appl Microbiol. 2010;72:63–87.CrossRefPubMed
30.
Vitetta L, Gobe G. Uremia and chronic kidney disease: the role of the gut microflora and therapies with pro- and prebiotics. Mol Nutr Food Res. 2013;57:824–832.CrossRefPubMed
31.
Wei M, Wang Z, Liu H, et al. Probiotic Bifidobacterium animalis subsp. lactis Bi-07 alleviates bacterial translocation and ameliorates microinflammation in experimental uraemia. Nephrology (Carlton). 2014;19:500–506.CrossRef
32.
Velasquez MT, Centron P, Barrows I, Dwivedi R, Raj DS. Gut Microbiota and Cardiovascular Uremic Toxicities. Toxins (Basel). 2018;10:287.CrossRef
33.
Sabatino A, Regolisti G, Brusasco I, Cabassi A, Morabito S, Fiaccadori E. Alterations of intestinal barrier and microbiota in chronic kidney disease. Nephrol Dial Transplant. 2015;30:924–933.CrossRefPubMed
34.
Sabatino A, Regolisti G, Cosola C, Gesualdo L, Fiaccadori E. Intestinal microbiota in type 2 diabetes and chronic kidney disease. Curr Diab Rep. 2017;17:16.CrossRefPubMed
35.
Dehghani H, Heidari F, Mozaffari-Khosravi H, Nouri-Majelan N, Dehghani A. Synbiotic supplementations for azotemia in patients with chronic kidney disease: a randomized controlled trial. Iran J Kidney Dis. 2016;10:351–357.PubMed
36.
Stecher B, Chaffron S, Kappeli R, et al. Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria. PLoS Pathog. 2010;6:e1000711.CrossRefPubMedPubMedCentral
37.
Manichanh C, Rigottier-Gois L, Bonnaud E, et al. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut. 2006;55:205–211.CrossRefPubMedPubMedCentral
38.
Wieland A, Frank DN, Harnke B, Bambha K. Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2015;42:1051–1063.CrossRefPubMed
39.
40.
Mulligan ME. Epidemiology of Clostridium difficile-induced intestinal disease. Rev Infect Dis. 1984;6:S222–S228.CrossRefPubMed
41.
42.
Ardalan M, Vahed SZ. Gut microbiota and renal transplant outcome. Biomed Pharmacother. 2017;90:229–236.CrossRefPubMed
43.
44.
Al Khodor S, Shatat IF. Gut microbiome and kidney disease: a bidirectional relationship. Pediatr Nephrol. 2017;32:921–931.CrossRefPubMed
45.
Briskey D, Tucker P, Johnson DW, Coombes JS. The role of the gastrointestinal tract and microbiota on uremic toxins and chronic kidney disease development. Clin Exp Nephrol. 2017;21:7–15.CrossRefPubMed
46.
47.
Wanchai K, Pongchaidecha A, Chatsudthipong V, Chattipakorn SC, Chattipakorn N, Lungkaphin A. Role of gastrointestinal microbiota on kidney injury and the obese condition. Am J Med Sci. 2017;353:59–69.CrossRefPubMed
48.
Soleimani A, Zarrati Mojarrad M, Bahmani F, et al. Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects. Kidney Int. 2017;91:435–442.CrossRefPubMed
49.
50.
Wang IK, Wu YY, Yang YF, et al. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial. Benef Microbes. 2015;6:423–430.CrossRefPubMed
51.
Simoes-Silva L, Araujo R, Pestana M, Soares-Silva I, Sampaio-Maia B. The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis. Pharmacol Res. 2018;130:143–151.CrossRefPubMed
52.
Ranganathan N, Ranganathan P, Friedman EA, et al. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv Ther. 2010;27:634–647.CrossRefPubMed
53.
Guida B, Germano R, Trio R, et al. Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial. Nutr Metab Cardiovasc Dis. 2014;24:1043–1049.CrossRefPubMed
54.
Miranda Alatriste PV, Urbina Arronte R, Gomez Espinosa CO, Espinosa Cuevas MDLA. Effect of probiotics on human blood urea levels in patients with chronic renal failure. Nutr Hosp. 2014;29:582–590.PubMed
55.
Pavan M. Influence of prebiotic and probiotic supplementation on the progression of chronic kidney disease. Minerva Urol Nefrol. 2016;68:222–226.PubMed
56.
Cigarran Guldris S, Gonzalez Parra E, Cases Amenos A. Gut microbiota in chronic kidney disease. Nefrologia. 2017;37:9–19.CrossRefPubMed
57.
Anders HJ, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int. 2013;83:1010–1016.CrossRefPubMed
58.
Prakash S, Chang TM. Microencapsulated genetically engineered live E. coli DH5 cells administered orally to maintain normal plasma urea level in uremic rats. Nat Med. 1996;2:883–887.CrossRefPubMed
59.
Andrade-Oliveira V, Amano MT, Correa-Costa M, et al. Gut bacteria products prevent AKI induced by ischemia-reperfusion. J Am Soc Nephrol. 2015;26:1877–1888.CrossRefPubMedPubMedCentral
60.
Ranganathan N, Patel BG, Ranganathan P, et al. In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease. Asaio j. 2006;52:70–79.CrossRefPubMed
61.
Ranganathan N, Patel B, Ranganathan P, et al. Probiotic amelioration of azotemia in 5/6th nephrectomized Sprague-Dawley rats. Scientific World Journal. 2005;5:652–660.CrossRefPubMedPubMedCentral
62.
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4:e296.CrossRef
63.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.CrossRefPubMedPubMedCentral
64.
65.
66.
Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet. 1991;337:867–872.CrossRefPubMed
67.
Cruz-Mora J, Martinez-Hernandez NE, Martin del Campo-Lopez F, et al. Effects of a symbiotic on gut microbiota in Mexican patients with end-stage renal disease. J Ren Nutr. 2014;24:330–335.CrossRefPubMed
68.
Simenhoff ML, Dunn SR, Zollner GP, et al. Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried Lactobacillus acidophilus. Miner Electrolyte Metab. 1996;22:92–96.PubMed
69.
Nakabayashi I, Nakamura M, Kawakami K, et al. Effects of synbiotic treatment on serum level of p-cresol in haemodialysis patients: a preliminary study. Nephrol Dial Transplant. 2011;26:1094–1098.CrossRefPubMed
70.
Natarajan R, Pechenya B. Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. BioMed Res Int. 2014;2014:568571.PubMedPubMedCentral
71.
Viramontes-Horner D, Marquez-Sandoval F, Martin-del-Campo F, et al. Effect of a symbiotic gel (Lactobacillus acidophilus + Bifidobacterium lactis + inulin) on presence and severity of gastrointestinal symptoms in hemodialysis patients. J Ren Nutr. 2015;25:284–291.CrossRefPubMed
72.
Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. Hoboken: Wiley; 2011.
73.
74.
Lieske JC, Goldfarb DS, De Simone C, Regnier C. Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int. 2005;68:1244–1249.CrossRefPubMed
75.
76.
Wong J, Piceno YM, DeSantis TZ, Pahl M, Andersen GL, Vaziri ND. Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD. Am J Nephrol. 2014;39:230–237.CrossRefPubMed
77.
Tang WH, Wang Z, Kennedy DJ, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116:448–455.CrossRefPubMed
78.
Ichii O, Otsuka-Kanazawa S, Nakamura T, et al. Podocyte injury caused by indoxyl sulfate, a uremic toxin and aryl-hydrocarbon receptor ligand. PLoS One. 2014;9:e108448.CrossRefPubMedPubMedCentral
79.
Watanabe H, Miyamoto Y, Honda D, et al. p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int. 2013;83:582–592.CrossRefPubMed
80.
Thongprayoon C, Hatch S, Kaewput W, et al. The effects of probiotics on renal function and uremic toxins in patients with chronic kidney disease; a meta-analysis of randomized controlled trials. J Nephropathol. 2018;7:106–114.CrossRef
81.
Vanholder R, Gryp T, Glorieux G. Urea and chronic kidney disease: the comeback of the century? (in uraemia research). Nephrol Dial Transplant. 2018;33:4–12.CrossRefPubMed
82.
83.
Mafra D, Lobo JC, Barros AF, Koppe L, Vaziri ND, Fouque D. Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol. 2014;9:399–410.CrossRefPubMed
84.
Ranganathan N, Friedman EA, Tam P, Rao V, Ranganathan P, Dheer R. Probiotic dietary supplementation in patients with stage 3 and 4 chronic kidney disease: a 6-month pilot scale trial in Canada. Curr Med Res Opin. 2009;25:1919–1930.CrossRefPubMed
85.
Wu Y, Potempa LA, El Kebir D, Filep JG. C-reactive protein and inflammation: conformational changes affect function. Biol Chem. 2015;396:1181–1197.CrossRefPubMed
86.
Cano AE, Neil AK, Kang JY, et al. Gastrointestinal symptoms in patients with end-stage renal disease undergoing treatment by hemodialysis or peritoneal dialysis. Am J Gastroenterol. 2007;102:1990–1997.CrossRefPubMed
87.
Strid H, Simren M, Johansson AC, Svedlund J, Samuelsson O, Bjornsson ES. The prevalence of gastrointestinal symptoms in patients with chronic renal failure is increased and associated with impaired psychological general well-being. Nephrol Dial Transplant. 2002;17:1434–1439.CrossRefPubMed
88.
Bossola M, Luciani G, Rosa F, Tazza L. Appetite and gastrointestinal symptoms in chronic hemodialysis patients. J Ren Nutr. 2011;21:448–454.CrossRefPubMed
89.
Hungin AP, Mulligan C, Pot B, et al. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice—an evidence-based international guide. Aliment Pharmacol Ther. 2013;38:864–886.CrossRefPubMedPubMedCentral
90.
91.
Hungin APS, Mitchell CR, Whorwell P, et al. Systematic review: probiotics in the management of lower gastrointestinal symptoms—an updated evidence-based international consensus. Aliment Pharmacol Ther. 2018;47:1054–1070.CrossRefPubMedPubMedCentral
92.
Natarajan R, Pechenyak B, Vyas U, et al. Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. Biomed Res Int. 2014;2014:568571.PubMedPubMedCentral
Metadata
Title
Effects of Probiotics on Inflammation and Uremic Toxins Among Patients on Dialysis: A Systematic Review and Meta-Analysis
Authors
Charat Thongprayoon
Wisit Kaewput
Spencer T. Hatch
Tarun Bathini
Konika Sharma
Karn Wijarnpreecha
Patompong Ungprasert
Matthew D’Costa
Michael A. Mao
Wisit Cheungpasitporn
Publication date
01-02-2019
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2019
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-018-5243-9

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