Effects of Synbiotics and Probiotics Supplementation on Serum Levels of Endotoxin, Heat Shock Protein 70 Antibodies and Inflammatory Markers in Hemodialysis Patients: a Randomized Double-Blinded Controlled Trial

  • Neda Haghighat
  • Majid MohammadshahiEmail author
  • Shokouh Shayanpour
  • Mohammad Hossein Haghighizadeh


The aim of this study was to investigate the effects of probiotic and synbiotic supplementation on serum inflammatory markers, endotoxin, and anti-HSP70 in hemodialysis (HD) patients. This study was a randomized, double-blind, placebo-controlled trial. Seventy-five hemodialysis patients who met the inclusion and exclusion criteria were randomly assigned for 12 weeks to one of the three arms: synbiotics [n = 23; 15 g of prebiotics, 5 g of probiotic powder containing Lactobacillus acidophilus T16, Bifidobacterium bifidum BIA-6, Bifidobacterium lactis BIA-6, and Bifidobacterium longum LAF-5 (2.7 × 107 CFU/g each)], probiotics [n = 23; 5 g probiotics as in synbiotic group with 15 g of maltodextrin in the sachet as placebo], and placebo [n = 19; 20 g of maltodextrin in the sachet]. Blood and feces were collected at baseline and after intervention. Serum high sensitive C-reactive protein (hs-CRP), interleukin-6, endotoxin, and anti-heat shock protein 70 antibodies (anti-HSP70) were measured. The number of fecal colonies was determined using the plate-counting method. The mean serum level of hs-CRP, anti-HSP70, and endotoxin decreased significantly between groups (p = 0.007, p = 0.037, and p = 0.036, respectively). For the synbiotic group, the mean changes in hs-CRP and IL-6 were significantly lower than for the placebo (p < 0.001 and p < 0.001, respectively) and probiotic group (p = 0.011 and p = 0.008, respectively). Anti-HSP70 mean changes in the synbiotic and probiotic groups differed from the placebo group (p = 0.002 and p = 0.013, respectively). Administration of synbiotics was more effective than probiotics for improvement of inflammatory markers, endotoxin and anti-HSP70 serum levels. Trial registration number: IRCT2017041233393N1


Synbiotics Probiotics Hemodialysis Inflammation Anti-HSP70 


Compliance with Ethical Standards

The study was conducted according to the guidelines of the Helsinki Declaration and all procedures involving human patients were approved by the Ethics Committee of Ahvaz University of Medical Sciences (university ethics code: IR.AJUMF.REC.1395.812). Written informed consent was obtained from all patients before initiating the study.

Conflict of Interest

The authors declare that they have no conflicts of interest.


  1. 1.
    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:S49–S50CrossRefGoogle Scholar
  2. 2.
    Vaziri ND, Zhao Y-Y, Pahl MV (2015) Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant 31:737–746CrossRefGoogle Scholar
  3. 3.
    Lebherz-Eichinger D, Krenn CG, Roth GA (2013) Keratin 18 and heat-shock protein in chronic kidney disease. Adv Clin Chem 62:123–149CrossRefGoogle Scholar
  4. 4.
    Ghayour-Mobarhan M, Saber H, Ferns GA (2012) The potential role of heat shock protein 27 in cardiovascular disease. Clin Chim Acta 413:15–24CrossRefGoogle Scholar
  5. 5.
    Musiał K, Szprynger K, Szczepańska M, Zwolińska D (2009) Heat shock proteins in children and young adults on chronic hemodialysis. Pediatr Nephrol 24:2029–2034CrossRefGoogle Scholar
  6. 6.
    Musiał K, Szczepańska M, Szprynger K, Zwolińska D (2009) The impact of dialysis modality on serum heat shock proteins in children and young adults with chronic kidney disease. Kidney Blood Press Res 32:366–372CrossRefGoogle Scholar
  7. 7.
    Chow J (2002) Probiotics and prebiotics: a brief overview. J Ren Nutr 12:76–86CrossRefGoogle Scholar
  8. 8.
    Vaziri ND (2016) Effect of synbiotic therapy on gut–derived uremic toxins and the intestinal microbiome in patients with CKD. Clin J Am Soc Nephrol 11:199–201CrossRefGoogle Scholar
  9. 9.
    Moura C, Lollo P, Morato P, Amaya-Farfan J (2018) Dietary nutrients and bioactive substances modulate heat shock protein (HSP) expression: a review. Nutrients 10:683CrossRefGoogle Scholar
  10. 10.
    Winham DM, Hutchins AM (2011) Perceptions of flatulence from bean consumption among adults in 3 feeding studies. Nutr J 10:128CrossRefGoogle Scholar
  11. 11.
    Haghighat N, Mohammadshahi M, Shayanpour S, Haghighizadeh MH (2018) Effect of synbiotic and probiotic supplementation on serum levels of endothelial cell adhesion molecules in hemodialysis patients: a randomized control study. Probiotics Antimicrob Proteins.
  12. 12.
    Wang I-K, Wu Y-Y, Yang Y-F, Ting I-W, Lin C-C, Yen TH, Chen JH, Wang CH, Huang CC, Lin HC (2015) The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial. Benef Microbes 6:423–430CrossRefGoogle Scholar
  13. 13.
    Urao M, Fujimoto T, Lane GJ, Seo G-i, Takeshi M (1999) Does probiotics administration decrease serum endotoxin levels in infants? J Pediatr Surg 34:273–276CrossRefGoogle Scholar
  14. 14.
    De Preter V, Vanhoutte T, Huys G, Swings J, Rutgeerts P et al (2008) Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects. Aliment Pharmacol Ther 27:504–513CrossRefGoogle Scholar
  15. 15.
    Schiffrin EJ, Parlesak A, Bode C, Bode JC, van't Hof MA et al (2008) Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions. Br J Nutr 101:961–966CrossRefGoogle Scholar
  16. 16.
    Sabico S, Al-Mashharawi A, Al-Daghri NM, Wani K, Amer OE et al (2018) Effects of a 6-month multi-strain probiotics supplementation in endotoxemic, inflammatory and cardiometabolic status of T2DM patients: a randomized, double-blind, placebo-controlled trial. Clin Nutr.
  17. 17.
    Sabico S, Al-Mashharawi A, Al-Daghri NM, Yakout S, Alnaami AM et al (2017) Effects of a multi-strain probiotic supplement for 12 weeks in circulating endotoxin levels and cardiometabolic profiles of medication naïve T2DM patients: a randomized clinical trial. J Transl Med 15:249CrossRefGoogle Scholar
  18. 18.
    McFarlane C, Ramos CI, Johnson DW, Campbell KL (2018) Prebiotic, probiotic, and synbiotic supplementation in chronic kidney disease: a systematic review and meta-analysis. J Ren Nutr.
  19. 19.
    Borges NA, Carmo FL, Stockler-Pinto MB, de Brito JS, Dolenga CJ, Ferreira DC, Nakao LS, Rosado A, Fouque D, Mafra D (2018) Probiotic supplementation in chronic kidney disease: a double-blind, randomized, placebo-controlled trial. J Ren Nutr 28:28–36CrossRefGoogle Scholar
  20. 20.
    Natarajan R, Pechenyak B, Vyas U, Ranganathan P, Weinberg A, Liang P, Mallappallil MC, Norin AJ, Friedman EA, Saggi SJ (2014) Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. Biomed Res Int 2014:568571PubMedPubMedCentralGoogle Scholar
  21. 21.
    Vaziri ND, Goshtasbi N, Yuan J, Jellbauer S, Moradi H, Raffatellu M, Kalantar-Zadeh K (2012) Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium. Am J Nephrol 36:438–443CrossRefGoogle Scholar
  22. 22.
    Mafra D, Lobo JC, Barros AF, Koppe L, Vaziri ND, Fouque D (2014) Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol 9:399–410CrossRefGoogle Scholar
  23. 23.
    Xie L-M, Ge Y-Y, Huang X, Zhang Y-Q, Li J-X (2015) Effects of fermentable dietary fiber supplementation on oxidative and inflammatory status in hemodialysis patients. Int J Clin Exp Med 8:1363–1369PubMedPubMedCentralGoogle Scholar
  24. 24.
    Hunter-Lavin C, Hudson PR, Mukherjee S, Davies GK, Williams CP, Harvey JN, Child DF, Williams JHH (2004) Folate supplementation reduces serum hsp70 levels in patients with type 2 diabetes. Cell Stress Chaperones 9:344–349CrossRefGoogle Scholar
  25. 25.
    Leng X, Wang X, Pang W, Zhan R, Zhang Z, Wang L, Gao X, Qian L (2013) Evidence of a role for both anti-Hsp70 antibody and endothelial surface membrane Hsp70 in atherosclerosis. Cell Stress Chaperones 18:483–493CrossRefGoogle Scholar
  26. 26.
    Zilaee M, Kermany T, Tavalaee S, Salehi M, Ghayour-Mobarhan M, Ferns GAA (2014) Barberry treatment reduces serum anti-heat shock protein 27 and 60 antibody titres and high-sensitivity C-reactive protein in patients with metabolic syndrome: a double-blind, randomized placebo-controlled trial. Phytother Res 28:1211–1215CrossRefGoogle Scholar
  27. 27.
    Moohebati M, Bidmeshgi S, Azarpazhooh MR, Daloee MH, Ghayour-Mobarhan M, Tavallaie S, Amini M, Momenzadeh A, Sahebkar A, Paydar R, Rahsepar AA, Parizadeh SMR, Akhlaghi S, Ferns GAA (2011) Simvastatin treatment reduces heat shock protein 60, 65, and 70 antibody titers in dyslipidemic patients: a randomized, double-blind, placebo-controlled, cross-over trial. Clin Biochem 44:192–197CrossRefGoogle Scholar
  28. 28.
    Shemshian M, Mousavi SH, Norouzy A, Kermani T, Moghiman T et al (2014) Saffron in metabolic syndrome: its effects on antibody titers to heat-shock proteins 27, 60, 65 and 70. J Complement Integr Med 11:43–49PubMedGoogle Scholar
  29. 29.
    Kelly G (2008) Inulin-type prebiotics--a review: part 1. Altern Med Rev 13:315–329PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Neda Haghighat
    • 1
  • Majid Mohammadshahi
    • 1
    • 2
    Email author
  • Shokouh Shayanpour
    • 3
  • Mohammad Hossein Haghighizadeh
    • 4
  1. 1.Nutrition and Metabolic Diseases Research CenterAhvaz Jundishapur University of Medical SciencesAhvazIran
  2. 2.Hyperlipidemia Research CenterAhvaz Jundishapur University of Medical SciencesAhvazIran
  3. 3.Department of Nephrology, Golestan HospitalAhvaz Jundishapur University of Medical SciencesAhvazIran
  4. 4.Department of Biostatistics and Epidemiology, Faculty of Public HealthAhvaz Jundishapur University of Medical SciencesAhvazIran

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