Gut microbiota and chronic kidney disease: implications for novel mechanistic insights and therapeutic strategies

International Urology and Nephrology

Volumn 50, Issue 2, 2018, Pages 289-299

  Pan, Wei ^a   Kang, Yongbo ^a  

^a KUNMING UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

Author keywords

Chronic kidney disease (CKD); Immune deregulation; Intestinal microbiota; Lipopolysaccharides (LPS); Prebiotic; Probiotics; Uremic toxins

Indexed keywords

ACARBOSE; LIPOPOLYSACCHARIDE; PREBIOTIC AGENT; PROBIOTIC AGENT; SYNBIOTIC AGENT; UREMIC TOXIN;

CHRONIC KIDNEY FAILURE; DISEASE COURSE; GASTROINTESTINAL TRACT; HUMAN; IMMUNE DYSREGULATION; INTESTINE FLORA; KIDNEY FAILURE; MICROBIAL COLONIZATION; NONHUMAN; PATHOGENESIS; REVIEW; DRUG EFFECT; IMMUNOLOGY; MICROBIOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; TREATMENT OUTCOME;

GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL TRACT; HUMANS; PROBIOTICS; RENAL INSUFFICIENCY, CHRONIC; TREATMENT OUTCOME;

EID: 85028550175     PISSN: 03011623     EISSN: 15732584     Source Type: Journal    
DOI: 10.1007/s11255-017-1689-5     Document Type: Review

References (125)

1. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR et al (2013) Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 382(9889):339–352
2. Evenepoel P, Meijers BK, Bammens BR et al (2009) Uremic toxins originating from colonic microbial metabolism. Kidney Int 76:S12–S19
3. Anders H-J, Andersen K, Stecher B (2013) The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int 83(6):1010–1016
4. Szeto C-C, Kwan BC-H, Chow K-M et al (2008) Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients. Clin J Am Soc Nephrol 3(2):431–436
5. Housman A, Shropshire Lad A Incidence and prevalence. United States Renal Data System. In: Proceedings of the 2010 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States, vol 2. Atlas of ESRD
6. Cerf-Bensussan N, Eberl G (2012) The dialog between microbiota and the immune system: shaping the partners through development and evolution. Semin Immunol 24(1):1–2
7. Gonçalves S, Pecoits-Filho R, Perreto S et al (2006) Associations between renal function, volume status and endotoxaemia in chronic kidney disease patients. Nephrol Dial Transplant 21(10):2788–2794
8. Le Chatelier E, Nielsen T, Qin J et al (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500(7464):541–546
9. Cani PD, Delzenne NM (2009) The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des 15(13):1546–1558
10. Vaziri ND (2012) CKD impairs barrier function and alters microbial flora of the intestine: a major link to inflammation and uremic toxicity. Curr Opin Nephrol Hypertens 21(6):587
11. Bäckhed F, Ley RE, Sonnenburg JL et al (2005) Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920
12. Hooper LV, Midtvedt T, Gordon JI (2002) How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 22(1):283–307
13. Ley RE, Turnbaugh PJ, Klein S et al (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022
14. Lam V, Su J, Koprowski S et al (2012) Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J 26(4):1727–1735
15. Wang Z, Klipfell E, Bennett BJ et al (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472(7341):57–63
16. ®, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis. Nephron 74(2):349–355
17. Simenhoff M, Dunn S, Zollner G et al (1995) 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 22(1–3):92–96
18. Vaziri ND, Wong J, Pahl M et al (2013) Chronic kidney disease alters intestinal microbial flora. Kidney Int 83(2):308–315
19. Aron-Wisnewsky J, Clément K (2016) The gut microbiome, diet, and links to cardiometabolic and chronic disorders. Nat Rev Nephrol 12(3):169–181
20. Mafra D, Lobo JC, Barros AF et al (2014) Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol 9(3):399–410
21. Sabatino A, Regolisti G, Brusasco I et al (2015) Alterations of intestinal barrier and microbiota in chronic kidney disease. Nephrol Dial Transplant 30(6):924–933
22. Carrero JJ, Stenvinkel P (2009) Persistent inflammation as a catalyst for other risk factors in chronic kidney disease: a hypothesis proposal. Clin J Am Soc Nephrol 4(Supplement 1):S49–S55
23. Neirynck N, Vanholder R, Schepers E et al (2013) An update on uremic toxins. Int Urol Nephrol 45(1):139–150
24. Sirich TL, Funk BA, Plummer NS et al (2014) Prominent accumulation in hemodialysis patients of solutes normally cleared by tubular secretion. J Am Soc Nephrol 25(3):615–622
25. Soulage CO, Koppe L, Fouque D (2013) Protein-bound uremic toxins… new targets to prevent insulin resistance and dysmetabolism in patients with chronic kidney disease. J Ren Nutr 23(6):464–466
26. Hughes R, Magee E, Bingham S (2000) Protein degradation in the large intestine: relevance to colorectal cancer. Curr Issues Intest Microbiol 1(2):51–58
27. Meijers BK, Verbeke K, Dehaen W et al (2009) The uremic retention solute p-cresyl sulfate and markers of endothelial damage. Am J Kidney Dis 54(5):891–901
28. Meijers BK, Claes K, Bammens B et al (2010) p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin J Am Soc Nephrol 5(7):1182–1189
29. Koppe L, Pillon NJ, Vella RE et al (2013) p-Cresyl sulfate promotes insulin resistance associated with CKD. J Am Soc Nephrol 24(1):88–99
30. Mutsaers HA, Stribos EG, Glorieux G et al (2015) Chronic kidney disease and fibrosis: the role of uremic retention solutes. Front Med 2:60
31. Meijers BK, Evenepoel P (2011) The gut–kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant 26(3):759–761
32. Barreto FC, Barreto DV, Liabeuf S et al (2009) Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol 4(10):1551–1558
33. Raff AC, Meyer TW, Hostetter TH (2008) New insights into uremic toxicity. Curr Opin Nephrol Hypertens 17(6):560–565
34. Faure V, Dou L, Sabatier F et al (2006) Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost 4(3):566–573
35. Tumur Z, Shimizu H, Enomoto A et al (2010) Indoxyl sulfate upregulates expression of ICAM-1 and MCP-1 by oxidative stress-induced NF-ĸB activation. Am J Nephrol 31(5):435–441
36. Lekawanvijit S, Adrahtas A, Kelly DJ et al (2010) Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? Eur Heart J 31(14):1771–1779
37. Aoki K, Teshima Y, Kondo H et al (2015) Role of indoxyl sulfate as a predisposing factor for atrial fibrillation in renal dysfunction. J Am Heart Assoc 4(10):e002023
38. Gross P, Massy ZA, Henaut L et al (2015) Para-cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling. J Cell Physiol 230(12):2927–2935
39. Lin C-J, Pan C-F, Liu H-L et al (2012) The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis. Atherosclerosis 225(1):173–179
40. Lin C-J, Wu V, Wu P-C et al (2015) Meta-analysis of the associations of p-cresyl sulfate (PCS) and indoxyl sulfate (IS) with cardiovascular events and all-cause mortality in patients with chronic renal failure. PLoS ONE 10(7):e0132589
41. Nii-Kono T, Iwasaki Y, Uchida M et al (2007) Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells. Kidney Int 71(8):738–743
42. Lin C-J, Pan C-F, Chuang C-K et al (2014) Association of indoxyl sulfate with fibroblast growth factor 23 in patients with advanced chronic kidney disease. Am J Med Sci 347(5):370–376
43. Hirata J, Hirai K, Asai H et al (2015) Indoxyl sulfate exacerbates low bone turnover induced by parathyroidectomy in young adult rats. Bone 79:252–258
44. Howitt MR, Garrett WS (2012) A complex microworld in the gut: gut microbiota and cardiovascular disease connectivity. Nat Med 18(8):1188–1189
45. Koeth RA, Wang Z, Levison BS et al (2013) Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19(5):576–585
46. Rak K, Rader DJ (2011) Cardiovascular disease: the diet-microbe morbid union. Nature 472(7341):40–41
47. Stubbs JR, House JA, Ocque AJ et al (2016) Serum trimethylamine-N-oxide is elevated in CKD and correlates with coronary atherosclerosis burden. J Am Soc Nephrol 27(1):305–313
48. Missailidis C, Hällqvist J, Qureshi AR et al (2016) Serum trimethylamine-N-oxide is strongly related to renal function and predicts outcome in chronic kidney disease. PLoS ONE 11(1):e0141738
49. Kaysen GA, Johansen KL, Chertow GM et al (2015) Associations of trimethylamine N-oxide with nutritional and inflammatory biomarkers and cardiovascular outcomes in patients new to dialysis. J Ren Nutr 25(4):351–356
50. Saito A, Takagi T, Chung T et al (1983) Serum levels of polyamines in patients with chronic renal failure. Kidney Int 16:S234–S237
51. Lutz W (1979) A uremic peptide containing polyamine: formation and possible role in uremic hypertriglyceridemia. Physiol Chem Phys 12(5):451–456
52. Chiang C-K, Tanaka T, Inagi R et al (2011) Indoxyl sulfate, a representative uremic toxin, suppresses erythropoietin production in a HIF-dependent manner. Lab Investig 91(11):1564–1571
53. Nangaku M, Mimura I, Yamaguchi J et al (2015) Role of uremic toxins in erythropoiesis-stimulating agent resistance in chronic kidney disease and dialysis patients. J Ren Nutr 25(2):160–163
54. Ahmed MSE, Abed M, Voelkl J et al (2013) Triggering of suicidal erythrocyte death by uremic toxin indoxyl sulfate. BMC Nephrol 14(1):244
55. Yoshida K, Yoneda T, Kimura S et al (2006) Polyamines as an inhibitor on erythropoiesis of hemodialysis patients by in vitro bioassay using the fetal mouse liver assay. Ther Apheresis Dial 10(3):267–272
56. Cario E, Gerken G, Podolsky D (2007) Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 132(4):1359–1374
57. Schlee M, Harder J, Köten B et al (2008) Probiotic lactobacilli and VSL# 3 induce enterocyte β-defensin 2. Clin Exp Immunol 151(3):528–535
58. Kiechl S, Lorenz E, Reindl M et al (2002) Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 347(3):185–192
59. Muccioli GG, Naslain D, Bäckhed F et al (2010) The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol 6(1):392
60. Sivapalaratnam S, Farrugia R, Nieuwdorp M et al (2011) Identification of candidate genes linking systemic inflammation to atherosclerosis; results of a human in vivo LPS infusion study. BMC Med Genomics 4(1):64
61. Ryu M, Kulkarni OP, Radomska E et al (2011) Bacterial CpG-DNA accelerates Alport glomerulosclerosis by inducing an M1 macrophage phenotype and tumor necrosis factor-α-mediated podocyte loss. Kidney Int 79(2):189–198
62. Patole PS, Pawar RD, Lichtnekert J et al (2007) Coactivation of Toll-like receptor-3 and -7 in immune complex glomerulonephritis. J Autoimmun 29(1):52–59
63. Farhadi A, Banan A, Fields J et al (2003) Intestinal barrier: an interface between health and disease. J Gastroenterol Hepatol 18(5):479–497
64. Magnusson M, Magnusson K-E, Sundqvist T et al (1990) Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low-and high-protein diets. Nephron 56(3):306–311
65. Magnusson M, Magnusson K, Sundqvist T et al (1991) Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. Gut 32(7):754–759
66. Kang J (1993) The gastrointestinal tract in uremia. Dig Dis Sci 38(2):257–268
67. de Almeida Duarte JB, de Aguilar-Nascimento JE, Nascimento M et al (2004) Bacterial translocation in experimental uremia. Urol Res 32(4):266–270
68. Vaziri ND, Yuan J, Nazertehrani S et al (2013) Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction. Am J Nephrol 38(2):99–103
69. Vaziri N, Dure-Smith B, Miller R et al (1985) Pathology of gastrointestinal tract in chronic hemodialysis patients: an autopsy study of 78 cases. Am J Gastroenterol 80(8):608–611
70. Ding L-A, Li J-S (2003) Gut in diseases: physiological elements and their clinical significance. World J Gastroenterol 9(11):2385–2389
71. Wang F, Zhang P, Jiang H et al (2012) Gut bacterial translocation contributes to microinflammation in experimental uremia. Dig Dis Sci 57(11):2856–2862
72. Wang F, Jiang H, Shi K et al (2012) Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology 17(8):733–738
73. Alegre ML, Mannon RB, Mannon PJ (2014) The microbiota, the immune system and the allograft. Am J Transplant 14(6):1236–1248
74. Bromberg JS, Fricke WF, Brinkman CC et al (2015) Microbiota [mdash] implications for immunity and transplantation. Nat Rev Nephrol 11(6):342–353
75. Stenvinkel P (2005) Inflammation in end-stage renal disease–a fire that burns within. Contrib Nephrol 149:185–199
76. Kato S, Chmielewski M, Honda H et al (2008) Aspects of immune dysfunction in end-stage renal disease. Clin J Am Soc Nephrol 3(5):1526–1533
77. Stearns-Kurosawa DJ, Osuchowski MF, Valentine C et al (2011) The pathogenesis of sepsis. Annu Rev Pathol Mech Dis 6:19–48
78. Carrero JJ, Stenvinkel P (2010) Inflammation in end-stage renal disease—What have we learned in 10 years? Semin Dial 23(5):498–509
79. Harris K, Kassis A, Major G et al (2012) Is the gut microbiota a new factor contributing to obesity and its metabolic disorders? J Obes 2012:879151
80. Chow J, Tang H, Mazmanian SK (2011) Pathobionts of the gastrointestinal microbiota and inflammatory disease. Curr Opin Immunol 23(4):473–480
81. Maslowski KM, Mackay CR (2011) Diet, gut microbiota and immune responses. Nat Immunol 12(1):5–9
82. Wen L, Ley RE, Volchkov PY et al (2008) Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455(7216):1109–1113
83. Macpherson AJ, Harris NL (2004) Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4(6):478–485
84. Kranich J, Maslowski KM, Mackay CR (2011) Commensal flora and the regulation of inflammatory and autoimmune responses. Semin Immunol 23(2):139–145
85. Niebauer J, Volk H-D, Kemp M et al (1999) Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 353(9167):1838–1842
86. McIntyre CW, Harrison LE, Eldehni MT et al (2011) Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol 6(1):133–141
87. Lee YK, Menezes JS, Umesaki Y et al (2011) Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci 108(Supplement 1):4615–4622
88. Vaziri ND, Pahl MV, Crum A et al (2012) Effect of uremia on structure and function of immune system. J Ren Nutr 22(1):149–156
89. Janus N, Vacher L-V, Karie S et al (2008) Vaccination and chronic kidney disease. Nephrol Dial Transplant 23(3):800–807
90. Hotchkiss RS, Coopersmith CM, McDunn JE et al (2009) The sepsis seesaw: tilting toward immunosuppression. Nat Med 15(5):496–497
91. Mutsaers HA, Engelke UF, Wilmer MJ et al (2013) Optimized metabolomic approach to identify uremic solutes in plasma of stage 3–4 chronic kidney disease patients. PLoS ONE 8(8):e71199
92. Konstantinov SR, Smidt H, de Vos WM et al (2008) S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc Natl Acad Sci 105(49):19474–19479
93. Van Baarlen P, Troost FJ, van Hemert S et al (2009) Differential NF-κB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance. Proc Natl Acad Sci 106(7):2371–2376
94. Murthy M, Venkitanarayan K, Rangavajhyala N et al (2000) Delineation of beneficial characteristics of effective probiotics. JAMA 3(2):38–43
95. Chen L, Liu W, Li Y et al (2013) Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process. Int Immunopharmacol 17(1):108–115
96. Ranganathan N, Patel B, Ranganathan P et al (2005) Probiotic amelioration of azotemia in 5/6th nephrectomized Sprague-Dawley rats. Sci World J 5:652–660
97. Ranganathan N, Patel BG, Ranganathan P et al (2006) In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease. ASAIO J 52(1):70–79
98. Niwa T (2011) Role of indoxyl sulfate in the progression of chronic kidney disease and cardiovascular disease: experimental and clinical effects of oral sorbent AST-120. Ther Apheresis Dial 15(2):120–124
99. Ueda H, Shibahara N, Takagi S et al (2008) AST-120 treatment in pre-dialysis period affects the prognosis in patients on hemodialysis. Ren Fail 30(9):856–860
100. Takayama F, Taki K, Niwa T (2003) Bifidobacterium in gastro-resistant seamless capsule reduces serum levels of indoxyl sulfate in patients on hemodialysis. Am J Kidney Dis 41(3):S142–S145
101. Taki K, Takayama F, Niwa T (2005) Beneficial effects of Bifidobacteria in a gastroresistant seamless capsule on hyperhomocysteinemia in hemodialysis patients. J Ren Nutr 15(1):77–80
102. Piñero-Lambea C, Ruano-Gallego D, Fernández LÁ (2015) Engineered bacteria as therapeutic agents. Curr Opin Biotechnol 35:94–102
103. Mandell DJ, Lajoie MJ, Mee MT et al (2015) Biocontainment of genetically modified organisms by synthetic protein design. Nature 518(7537):55–60
104. Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125(6):1401
105. Gibson GR, Probert HM, Van Loo J et al (2004) Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev 17(02):259–275
106. Silk D, Davis A, Vulevic J et al (2009) Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 29(5):508–518
107. Meijers BK, De Preter V, Verbeke K et al (2010) p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin. Nephrol Dial Transplant 25(1):219–224
108. Salmean YA, Segal MS, Langkamp-Henken B et al (2013) Foods with added fiber lower serum creatinine levels in patients with chronic kidney disease. J Ren Nutr 23(2):e29–e32
109. Cani PD, Neyrinck A, Fava F et al (2007) Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50(11):2374–2383
110. Broekaert WF, Courtin CM, Verbeke K et al (2011) Prebiotic and other health-related effects of cereal-derived arabinoxylans, arabinoxylan-oligosaccharides, and xylooligosaccharides. Crit Rev Food Sci Nutr 51(2):178–194
111. Gibson GR, Beatty ER, Wang X et al (1995) Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology 108(4):975–982
112. Pylkas AM, Juneja LR, Slavin JL (2005) Comparison of different fibers for in vitro production of short chain fatty acids by intestinal microflora. J Med Food 8(1):113–116
113. Reimer R, McBURNEY MI (1996) Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon-like peptide-1 and insulin in rats. Endocrinology 137(9):3948–3956
114. Dumoulin V, Moro F, Barcelo A et al (1998) Peptide YY, glucagon-like peptide-1, and neurotensin responses to luminal factors in the isolated vascularly perfused rat ileum. Endocrinology 139(9):3780–3786
115. Drucker DJ (2006) The biology of incretin hormones. Cell Metab 3(3):153–165
116. Ranganath L, Beety J, Morgan L et al (1996) Attenuated GLP-1 secretion in obesity: cause or consequence? Gut 38(6):916–919
117. Batterham RL, Cowley MA, Small CJ et al (2002) Gut hormone PYY3-36 physiologically inhibits food intake. Nature 418(6898):650
118. Delzenne NM, Cani PD, Daubioul C et al (2005) Impact of inulin and oligofructose on gastrointestinal peptides. Br J Nutr 93(S1):S157–S161
119. Alimentarius C (2010) Guidelines on nutrition labelling CAC/GL 2-1985 as last amended 2010. Joint FAO/WHO Food Standards Programme, Secretariat of the Codex Alimentarius Commission, FAO, Rome
120. Chiavaroli L, Mirrahimi A, Sievenpiper J et al (2015) Dietary fiber effects in chronic kidney disease: a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr 69(7):761
121. Vaziri ND, Liu S-M, Lau WL et al (2014) High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PLoS ONE 9(12):e114881
122. Sirich TL, Plummer NS, Gardner CD et al (2014) Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients. Clin J Am Soc Nephrol 9(9):1603–1610
123. Evenepoel P, Bammens B, Verbeke K et al (2006) Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: a pilot study. Kidney Int 70(1):192–198
124. Rossi M, Johnson DW, Morrison M et al (2016) Synbiotics easing renal failure by improving gut microbiology (SYNERGY): a randomized trial. Clin J Am Soc Nephrol 11(2):223–231
125. Nakabayashi I, Nakamura M, Kawakami K et al (2011) Effects of synbiotic treatment on serum level of p-cresol in haemodialysis patients: a preliminary study. Nephrol Dial Transplant 26(3):1094–1098