This study was conducted to evaluate the effects of synbiotic supplementation on metabolic profiles in diabetic patients undergoing hemodialysis (HD). This randomized, double-blinded, placebo-controlled clinical trial was performed in 60 diabetic HD patients. Participants were randomly assigned into two groups to receive either synbiotic capsule, containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum (2 × 109 CFU/g each), plus 0.8 g/day of inulin (n = 30) or placebo (n = 30) for 12 weeks. Synbiotic supplementation significantly decreased fasting plasma glucose (β − 13.56 mg/dL; 95% CI, − 23.82, − 3.30; P = 0.01), insulin levels (β − 5.49 μIU/mL; 95% CI, − 6.92, − 4.05; P < 0.001), and insulin resistance (β − 2.25; 95% CI, − 3.02, − 1.48; P < 0.001), while increased the quantitative insulin sensitivity check index (β 0.02; 95% CI, 0.01, 0.02; P < 0.001) compared with the placebo. Additionally, synbiotic intake resulted in a significant reduction in high-sensitivity C-reactive protein (β − 2930.48 ng/mL; 95% CI, − 3741.15, − 2119.80; P < 0.001) and malondialdehyde levels (β − 0.60 μmol/L; 95% CI, − 0.99, − 0.20; P = 0.003). Moreover, we found a significant increase in total antioxidant capacity (β 142.99 mmol/L; 95% CI, 61.72, 224.25; P = 0.001) and total glutathione levels (β 131.11 μmol/L; 95% CI, 89.35, 172.87; P < 0.001) in the synbiotic group compared with the placebo group. Overall, synbiotic supplementation for 12 weeks had beneficial effects on glycemic control, biomarkers of inflammation, and oxidative stress in diabetic patients under HD. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT2017090133941N17). http://www.irct.ir: IRCT2017090133941N17.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
end-stage renal disease
fasting plasma glucose
homeostasis model of assessment-insulin resistance
high-sensitivity C-reactive protein
quantitative insulin sensitivity check index
short-chain fatty acids
subjective global assessment
type 2 diabetes mellitus
total antioxidant capacity
Sabatino A, Regolisti G, Cosola C, Gesualdo L, Fiaccadori E (2017) Intestinal microbiota in type 2 diabetes and chronic kidney disease. Curr Diab Rep 17:16. https://doi.org/10.1007/s11892-017-0841-z
Whaley-Connell A, Sowers JR (2017) Insulin resistance in kidney disease: is there a distinct role separate from that of diabetes or obesity? Cardiorenal Med 8:41–49. https://doi.org/10.1159/000479801
March DS, Graham-Brown MP, Stover CM, Bishop NC, Burton JO (2017) Intestinal barrier disturbances in haemodialysis patients: mechanisms, consequences, and therapeutic options. Biomed Res Int 2017:5765417–5765411. https://doi.org/10.1155/2017/5765417
Chen Z, Zhu S, Xu G (2016) Targeting gut microbiota: a potential promising therapy for diabetic kidney disease. Am J Transl Res 8:4009–4016
Markowiak P, Slizewska K (2017) Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients 9. https://doi.org/10.3390/nu9091021
Krumbeck JA, Maldonado-Gomez MX, Ramer-Tait AE, Hutkins RW (2016) Prebiotics and synbiotics: dietary strategies for improving gut health. Curr Opin Gastroenterol 32:110–119. https://doi.org/10.1097/MOG.0000000000000249
Cruz-Mora J, Martinez-Hernandez NE, Martin del Campo-Lopez F, Viramontes-Hörner D, Vizmanos-Lamotte B, Muñoz-Valle JF, García-García G, Parra-Rojas I, Castro-Alarcón N (2014) Effects of a symbiotic on gut microbiota in Mexican patients with end-stage renal disease. J Ren Nutr 24:330–335. https://doi.org/10.1053/j.jrn.2014.05.006
Asemi Z, Alizadeh SA, Ahmad K, Goli M, Esmaillzadeh A (2016) Effects of beta-carotene fortified synbiotic food on metabolic control of patients with type 2 diabetes mellitus: a double-blind randomized cross-over controlled clinical trial. Clin Nutr 35:819–825. https://doi.org/10.1016/j.clnu.2015.07.009
Hadi A, Mohammadi H, Miraghajani M, Ghaedi E (2018) Efficacy of synbiotic supplementation in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis of clinical trials. Crit Rev Food Sci Nutr 27:1–12. https://doi.org/10.1080/10408398.2018.1458021.
Zamani B, Farshbaf S, Golkar HR, Bahmani F, Asemi Z (2017) Synbiotic supplementation and the effects on clinical and metabolic responses in patients with rheumatoid arthritis: a randomised, double-blind, placebo-controlled trial. Br J Nutr 117:1095–1102. https://doi.org/10.1017/S000711451700085X
Beserra BT, Fernandes R, do Rosario VA, Mocellin MC, Kuntz MG, Trindade EB (2015) A systematic review and meta-analysis of the prebiotics and synbiotics effects on glycaemia, insulin concentrations and lipid parameters in adult patients with overweight or obesity. Clin Nutr 34:845–858. https://doi.org/10.1016/j.clnu.2014.10.004
Tabrizi R, Moosazadeh M, Lankarani KB, Akbari M, Heydari ST, Kolahdooz F, Asemi Z (2017) The effects of synbiotic supplementation on glucose metabolism and lipid profiles in patients with diabetes: a systematic review and meta-analysis of randomized controlled trials. Probiotics Antimicrob Proteins 10:329–342. https://doi.org/10.1007/s12602-017-9299-1
Taghizadeh M, Asemi Z (2014) Effects of synbiotic food consumption on glycemic status and serum hs-CRP in pregnant women: a randomized controlled clinical trial. Hormones (Athens) 13:398–406. https://doi.org/10.14310/horm.2002.1489.
Shakeri H, Hadaegh H, Abedi F, Tajabadi-Ebrahimi M, Mazroii N, Ghandi Y, Asemi Z (2014) Consumption of synbiotic bread decreases triacylglycerol and VLDL levels while increasing HDL levels in serum from patients with type-2 diabetes. Lipids 49:695–701. https://doi.org/10.1007/s11745-014-3901-z
Eslamparast T, Zamani F, Hekmatdoost A, Sharafkhah M, Eghtesad S, Malekzadeh R, Poustchi H (2014) Effects of synbiotic supplementation on insulin resistance in subjects with the metabolic syndrome: a randomised, double-blind, placebo-controlled pilot study. Br J Nutr 112:438–445. https://doi.org/10.1017/S0007114514000919
Rajkumar H, Kumar M, Das N, Kumar SN, Challa HR, Nagpal R (2015) Effect of probiotic Lactobacillus salivarius UBL S22 and prebiotic fructo-oligosaccharide on serum lipids, inflammatory markers, insulin sensitivity, and gut bacteria in healthy young volunteers: a randomized controlled single-blind pilot study. J Cardiovasc Pharmacol Ther 20:289–298. https://doi.org/10.1177/1074248414555004
McNabney SM, Henagan TM (2017) Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer, obesity and insulin resistance. Nutrients 9. https://doi.org/10.3390/nu9121348
Miraghajani M, Dehsoukhteh SS, Rafie N, Hamedani SG, Sabihi S, Ghiasvand R (2017) Potential mechanisms linking probiotics to diabetes: a narrative review of the literature. Sao Paulo Med J 135:169–178. https://doi.org/10.1590/1516-3180.2016.0311271216
Soccol CR, de Souza Vandenberghe LP, Spier MR, Medeiros AP, Yamaguishi CT, De Dea Lindner J, Pandey A, Thomaz-Soccol V (2010) The potential of probiotics: a review. Food Technol Biotechnol 48:413–434
Farrokhian A, Raygan F, Soltani A, Tajabadi-Ebrahimi M, Sharifi Esfahani M, Karami AA, Asemi Z (2017) The effects of synbiotic supplementation on carotid intima-media thickness, biomarkers of inflammation, and oxidative stress in people with overweight, diabetes, and coronary heart disease: a randomized, double-blind, placebo-controlled trial. Probiotics Antimicrob Proteins. https://doi.org/10.1007/s12602-017-9343-1
Kelishadi R, Farajian S, Safavi M, Mirlohi M, Hashemipour M (2014) A randomized triple-masked controlled trial on the effects of synbiotics on inflammation markers in overweight children. J Pediatr 90:161–168. https://doi.org/10.1016/j.jped.2013.07.003
Pisprasert V, Ingram KH, Lopez-Davila MF, Munoz AJ, Garvey WT (2013) Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans. Diabetes Care 36:845–853. https://doi.org/10.2337/dc12-0840
Tatsch E, Bochi GV, Pereira Rda S, Kober H, Agertt VA, de Campos MM, Gomes P, Duarte MM, Moresco RN (2011) A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clin Biochem 44:348–350. https://doi.org/10.1016/j.clinbiochem.2010.12.011
Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76
Beutler E, Gelbart T (1985) Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med 105:581–584
Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9:515–540
Nursal TZ, Noyan T, Tarim A, Karakayali H (2005) A new weighted scoring system for subjective global assessment. Nutrition 21:666–671
Tajabadi-Ebrahimi M, Sharifi N, Farrokhian A, Raygan F, Karamali F, Razzaghi R, Taheri S, Asemi Z (2017) A randomized controlled clinical trial investigating the effect of synbiotic administration on markers of insulin metabolism and lipid profiles in overweight type 2 diabetic patients with coronary heart disease. Exp Clin Endocrinol Diabetes 125:21–27. https://doi.org/10.1055/s-0042-105441.
Soleimani A, Zarrati Mojarrad M, Bahmani F, Taghizadeh M, Ramezani M, Tajabadi-Ebrahimi M, Jafari P, Esmaillzadeh A, Asemi Z (2017) Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects. Kidney Int 91:435–442. https://doi.org/10.1016/j.kint.2016.09.040
Million M, Angelakis E, Paul M, Armougom F, Leibovici L, Raoult D (2012) Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals. Microb Pathog 53:100–108. https://doi.org/10.1016/j.micpath.2012.05.007
Heo J, Seo M, Park H, Lee WK, Guan LL, Yoon J, Caetano-Anolles K, Ahn H, Kim SY, Kang YM, Cho S, Kim H (2016) Gut microbiota modulated by probiotics and garcinia cambogia extract correlate with weight gain and adipocyte sizes in high fat-fed mice. Sci Rep 6:33566. https://doi.org/10.1038/srep33566
Carrero JJ, Stenvinkel P, Cuppari L, Ikizler TA, Kalantar-Zadeh K, Kaysen G, Mitch WE, Price SR, Wanner C, Wang AY, ter Wee P, Franch HA (2013) Etiology of the protein-energy wasting syndrome in chronic kidney disease: a consensus statement from the International Society of Renal Nutrition and Metabolism (ISRNM). J Ren Nutr 23:77–90. https://doi.org/10.1053/j.jrn.2013.01.001
Ikizler TA, Cano NJ, Franch H, Fouque D, Himmelfarb J, Kalantar-Zadeh K, Kuhlmann MK, Stenvinkel P, TerWee P, Teta D, Wang AY, Wanner C (2013) Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 84:1096–1107. https://doi.org/10.1038/ki.2013.147
Carrero JJ, Cabezas-Rodriguez I, Qureshi AR, Floege J, Ketteler M, London G, Locatelli F, Memmos D, Goldsmith D, Ferreira A, Nagy J, Teplan V, Martínez-Salgado C, Fernández-Martín JL, Zoccali C, Cannata-Andia JB, COSMOS group (2018) Risk of hospitalization associated with body mass index and weight changes among prevalent haemodialysis patients. Nefrologia 38:520–527. https://doi.org/10.1016/j.nefro.2018.02.009
Raoult D (2008) Human microbiome: take-home lesson on growth promoters? Nature 454:690–691. https://doi.org/10.1038/454690c
Delzenne N, Reid G (2009) No causal link between obesity and probiotics. Nat Rev Microbiol 7:901. https://doi.org/10.1038/nrmicro2209-c2
Moroti C, Souza Magri LF, de Rezende Costa M, Cavallini DC, Sivieri K (2012) Effect of the consumption of a new symbiotic shake on glycemia and cholesterol levels in elderly people with type 2 diabetes mellitus. Lipids Health Dis 11:29. https://doi.org/10.1186/1476-511X-11-29
Spoto B, Pisano A, Zoccali C (2016) Insulin resistance in chronic kidney disease: a systematic review. Am J Physiol Renal Physiol 311:F1087–f1108. https://doi.org/10.1152/ajprenal.00340.2016
Zha Y, Qian Q (2017) Protein nutrition and malnutrition in CKD and ESRD. Nutrients 9
Hommelberg PP, Langen RC, Schols AM, Mensink RP, Plat J (2010) Inflammatory signaling in skeletal muscle insulin resistance: green signal for nutritional intervention? Curr Opin Clin Nutr Metab Care 13:647–655. https://doi.org/10.1097/MCO.0b013e32833f1acd
Kleniewska P, Pawliczak R (2017) Influence of synbiotics on selected oxidative stress parameters. Oxidative Med Cell Longev 2017:9315375–9315378. https://doi.org/10.1155/2017/9315375
Kang YM, Lee BJ, Kim JI, Nam BH, Cha JY, Kim YM, Ahn CB, Choi JS, Choi IS, Je JY (2012) Antioxidant effects of fermented sea tangle (Laminaria japonica) by Lactobacillus brevis BJ20 in individuals with high level of gamma-GT: a randomized, double-blind, and placebo-controlled clinical study. Food Chem Toxicol 50:1166–1169. https://doi.org/10.1016/j.fct.2011.11.026
Pourghassem Gargari B, Dehghan P, Aliasgharzadeh A, Asghari Jafar-Abadi M (2013) Effects of high performance inulin supplementation on glycemic control and antioxidant status in women with type 2 diabetes. Diabetes Metab J 37:140–148. https://doi.org/10.4093/dmj.2013.37.2.140
Valentini L, Pinto A, Bourdel-Marchasson I, Ostan R, Brigidi P, Turroni S, Hrelia S, Hrelia P, Bereswill S, Fischer A, Leoncini E, Malaguti M, Blanc-Bisson C, Durrieu J, Spazzafumo L, Buccolini F, Pryen F, Donini LM, Franceschi C, Lochs H (2015) Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - the “RISTOMED project”: randomized controlled trial in healthy older people. Clin Nutr 34:593–602. https://doi.org/10.1016/j.clnu.2014.09.023
Mazloom Z, Yousefinejad A, Dabbaghmanesh MH (2013) Effect of probiotics on lipid profile, glycemic control, insulin action, oxidative stress, and inflammatory markers in patients with type 2 diabetes: a clinical trial. Iran J Med Sci 38:38–43
Karimi E, Moini A, Yaseri M, Shirzad N, Sepidarkish M, Hossein-Boroujerdi M, Hosseinzadeh-Attar MJ (2018) Effects of synbiotic supplementation on metabolic parameters and apelin in women with polycystic ovary syndrome: a randomised double-blind placebo-controlled trial. Br J Nutr 119:398–406. https://doi.org/10.1017/S0007114517003920
Zhang W, He J, Zhang F, Huang C, Wu Y, Han Y, Zhang W, Zhao Y (2013) Prognostic role of C-reactive protein and interleukin-6 in dialysis patients: a systematic review and meta-analysis. J Nephrol 26:243–253. https://doi.org/10.5301/jn.5000169
Allawi AAD (2018) Malnutrition, inflamation and atherosclerosis (MIA syndrome) in patients with end stage renal disease on maintenance hemodialysis (a single centre experience). Diabetes Metab Syndr 12:91–97. https://doi.org/10.1016/j.dsx.2017.09.003
Kobayashi M, Mikami D, Kimura H, Kamiyama K, Morikawa Y, Yokoi S, Kasuno K, Takahashi N, Taniguchi T, Iwano M (2017) Short-chain fatty acids, GPR41 and GPR43 ligands, inhibit TNF-alpha-induced MCP-1 expression by modulating p38 and JNK signaling pathways in human renal cortical epithelial cells. Biochem Biophys Res Commun 486:499–505
Plaza-Diaz J, Ruiz-Ojeda FJ, Vilchez-Padial LM, Gil A (2017) Evidence of the anti-inflammatory effects of probiotics and synbiotics in intestinal chronic diseases. Nutrients 9. https://doi.org/10.3390/nu9060555
Kalina U, Koyama N, Hosoda T, Nuernberger H, Sato K, Hoelzer D, Herweck F, Manigold T, Singer MV, Rossol S, Böcker U (2002) Enhanced production of IL-18 in butyrate-treated intestinal epithelium by stimulation of the proximal promoter region. Eur J Immunol 32:2635–2643
Vitali B, Ndagijimana M, Cruciani F, Carnevali P, Candela M, Guerzoni ME, Brigidi P (2010) Impact of a synbiotic food on the gut microbial ecology and metabolic profiles. BMC Microbiol 10:4. https://doi.org/10.1186/1471-2180-10-4
The present study was supported by a grant from the Vice-chancellor for Research, KAUMS, and Iran. The authors would like to thank the staff of Akhavan Clinic (Kashan, Iran) for their assistance in this project. The authors of this study would like to appreciate Dr. Naghmeh Mirhosseini for a scientific review and edition of the paper.
The research grant provided by Research Deputy of Kashan University of Medical Sciences (KAUMS).
Ethics Approval and Consent to Participate
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments.
Consent for Publication
Availability of Data and Material
The primary data for this study is available from the authors on direct request.
The authors declare that they have no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic Supplementary Material
About this article
Cite this article
Soleimani, A., Motamedzadeh, A., Zarrati Mojarrad, M. et al. The Effects of Synbiotic Supplementation on Metabolic Status in Diabetic Patients Undergoing Hemodialysis: a Randomized, Double-Blinded, Placebo-Controlled Trial. Probiotics & Antimicro. Prot. 11, 1248–1256 (2019). https://doi.org/10.1007/s12602-018-9499-3
- Synbiotic supplementation
- Metabolic status