Hostname: page-component-6587cd75c8-67gbf Total loading time: 0 Render date: 2025-04-24T03:04:14.966Z Has data issue: false hasContentIssue false

Effects of multi-species synbiotic supplementation on circulating miR-27a, miR-33a levels and lipid parameters in adult men with dyslipidaemia; a randomised, double-blind, placebo-controlled clinical trial

Published online by Cambridge University Press:  30 April 2024

Shekoufeh Salamat
Affiliation:
Nutrition and Metabolic Diseases Research Center, Clinical Sciences Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Alireza Jahan-Mihan
Affiliation:
Department of Nutrition and Dietetics, University of North Florida, Jacksonville, FL, USA
Mohammad Reza Tabandeh
Affiliation:
Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran Stem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Anahita Mansoori*
Affiliation:
Nutrition and Metabolic Diseases Research Center, Clinical Sciences Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
*
*Corresponding author: Dr Anahita Mansoori, email mansoori-a@ajums.ac.ir

Abstract

MicroRNAs (miRNAs) have emerged as important regulators of lipid metabolism. Recent studies have suggested synbiotics may modulate miRNA expression and lipid metabolism. This study aimed to investigate the effects of synbiotic supplementation on circulating miR-27a, miR-33a and lipid parameters in patients with dyslipidaemia. Fifty-six eligible participants were randomly allocated to receive either synbiotic or placebo sachets twice a day for 12 weeks. Each synbiotic sachet contained 3 × 1010 colony forming unit six species of probiotic microorganisms and 5 g of inulin and fructooligosaccharide as prebiotics. Serum miR-27a and miR-33a expression levels, serum lipids and apolipoproteins, the fecal concentration of short-chain fatty acids (SCFA) and Firmicutes and Bacteroidetes phyla were assessed before and after the study. Real-time PCR was used to determine the relative expression levels of miRNAs. The results showed synbiotic supplementation significantly downregulated the expression levels of miR-27a and miR-33a compared with the placebo group (P = 0·008 and P = 0·001, respectively). Furthermore, the intervention group exhibited significant improvements in serum HDL-cholesterol, small dense LDL (sdLDL-cholesterol), apoA-I and apoB-100 (P = 0·008, P = 0·006, P = 0·003, P = 0·001, respectively). The results showed a significant negative correlation between miR-33a expression levels with HDL-cholesterol, butyrate, propionate and a significant positive correlation with total cholesterol, LDL-cholesterol and sdLDL-cholesterol in the intervention group. Fecal bacteria and SCFA were significantly increased in the intervention group. This study provides evidence that synbiotic supplementation can modulate miR-27a and miR-33a expression and improve lipid metabolism in patients with dyslipidaemia.

Type
Research Article
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of The Nutrition Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Tabatabaei-Malazy, O, Qorbani, M, Samavat, T, et al. (2014) Prevalence of dyslipidemia in Iran: a systematic review and meta-analysis study. Int J Prev Med 5, 373.Google ScholarPubMed
Khanali, J, Ghasemi, E, Rashidi, M-M, et al. (2023) Prevalence of plasma lipid abnormalities and associated risk factors among Iranian adults based on the findings from STEPs survey 2021. Sci Rep 13, 15499.CrossRefGoogle ScholarPubMed
Dexheimer, PJ & Cochella, L (2020) MicroRNAs: from mechanism to organism. Front Cell Dev Biol 8, 409.CrossRefGoogle ScholarPubMed
Ono, K (2016) Functions of microRNA-33a/b and microRNA therapeutics. J Cardiol 67, 2833.CrossRefGoogle ScholarPubMed
Xiang, Y, Mao, L, Zuo, M-L, et al. (2022) The role of MicroRNAs in hyperlipidemia: from pathogenesis to therapeutical application. Mediators Inflamm 2022, 3101900.CrossRefGoogle ScholarPubMed
Fichtlscherer, S, De Rosa, S, Fox, H, et al. (2010) Circulating microRNAs in patients with coronary artery disease. Circ Res 107, 677684.CrossRefGoogle ScholarPubMed
Behrouzi, A, Ashrafian, F, Mazaheri, H, et al. (2020) The importance of interaction between MicroRNAs and gut microbiota in several pathways. Microb Pathog 144, 104200.CrossRefGoogle ScholarPubMed
Yang, Z, Cappello, T & Wang, L (2015) Emerging role of microRNAs in lipid metabolism. Acta Pharm Sin B 5, 145150.CrossRefGoogle ScholarPubMed
Rayner, KJ & Moore, KJ (2014) MicroRNA control of high-density lipoprotein metabolism and function. Circ Res 114, 183192.CrossRefGoogle ScholarPubMed
Singh, AK, Aryal, B, Zhang, X, et al. (2018) Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins. Semin Cell Dev Biol 81, 129140.CrossRefGoogle ScholarPubMed
Zhang, X, Price, NL & Fernández-Hernando, C (2019) Non-coding RNAs in lipid metabolism. VascPharmacol 114, 93102.Google ScholarPubMed
Khan, AA, Agarwal, H, Reddy, SS, et al. (2020) MicroRNA 27a is a key modulator of cholesterol biosynthesis. Mol Cell Biol 40, e0047000419.CrossRefGoogle ScholarPubMed
Flowers, E, Froelicher, ES & Aouizerat, BE (2013) MicroRNA regulation of lipid metabolism. Metabolism 62, 1220.CrossRefGoogle ScholarPubMed
Li, M, Chen, W-D & Wang, Y-D (2020) The roles of the gut microbiota–miRNA interaction in the host pathophysiology. Mol Med 26, 19.CrossRefGoogle ScholarPubMed
Xing, J, Liao, Y, Zhang, H, et al. (2022) Impacts of MicroRNAs induced by the gut microbiome on regulating the development of colorectal cancer. Front Cell Infect Microbiol 12, 424.CrossRefGoogle ScholarPubMed
Ionescu, RF, Enache, RM, Cretoiu, SM, et al. (2022) The interplay between gut microbiota and miRNAs in cardiovascular diseases. Front Cardiovasc Med 9, 856901.CrossRefGoogle ScholarPubMed
Flaig, B, Garza, R, Singh, B, et al. (2023) Treatment of dyslipidemia through targeted therapy of gut microbiota. Nutrients 15, 228.CrossRefGoogle ScholarPubMed
Lei, L, Zhao, N, Zhang, L, et al. (2022) Gut microbiota is a potential goalkeeper of dyslipidemia. Front Endocrinol 13, 950826.CrossRefGoogle ScholarPubMed
Bidell, MR, Hobbs, AL & Lodise, TP (2022) Gut microbiome health and dysbiosis: a clinical primer. Pharmacother: J Human Pharmacol Drug Ther 42, 849857.CrossRefGoogle ScholarPubMed
Carding, S, Verbeke, K, Vipond, DT, et al. (2015) Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis 26, 26191.Google ScholarPubMed
Sergeev, IN, Aljutaily, T, Walton, G, et al. (2020) Effects of synbiotic supplement on human gut microbiota, body composition and weight loss in obesity. Nutrients 12, 222.CrossRefGoogle ScholarPubMed
Arabi, SM, Bahrami, LS, Rahnama, I, et al. (2022) Impact of synbiotic supplementation on cardiometabolic and anthropometric indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 176, 106061.CrossRefGoogle ScholarPubMed
Zeinali, F, Aghaei Zarch, SM, Vahidi Mehrjardi, MY, et al. (2020) Effects of synbiotic supplementation on gut microbiome, serum level of TNF-α, and expression of microRNA-126 and microRNA-146a in patients with type 2 diabetes mellitus: study protocol for a double-blind controlled randomized clinical trial. Trials 21, 19.CrossRefGoogle ScholarPubMed
Hadi, A, Ghaedi, E, Khalesi, S, et al. (2020) Effects of synbiotic consumption on lipid profile: a systematic review and meta-analysis of randomized controlled clinical trials. Eur J Nutr 59, 28572874.CrossRefGoogle ScholarPubMed
Wang, L, Guo, M-J, Gao, Q, et al. (2018) The effects of probiotics on total cholesterol: a meta-analysis of randomized controlled trials. Medicine 97, e9679.CrossRefGoogle ScholarPubMed
Kullisaar, T, Zilmer, K, Salum, T, et al. (2016) The use of probiotic L. fermentum ME-3 containing Reg’Activ Cholesterol supplement for 4 weeks has a positive influence on blood lipoprotein profiles and inflammatory cytokines: an open-label preliminary study. Nutr J 15, 16.CrossRefGoogle Scholar
Fuentes, MC, Lajo, T, Carrión, JM, et al. (2013) Cholesterol-lowering efficacy of Lactobacillus plantarum CECT 7527, 7528 and 7529 in hypercholesterolaemic adults. Br J Nutr 109, 18661872.CrossRefGoogle Scholar
Xiao, J, Kondo, S, Takahashi, N, et al. (2003) Effects of milk products fermented by Bifidobacterium longum on blood lipids in rats and healthy adult male volunteers. J Dairy Sci 86, 24522461.CrossRefGoogle ScholarPubMed
Bernini, LJ, Simão, ANC, Alfieri, DF, et al. (2016) Beneficial effects of Bifidobacterium lactis on lipid profile and cytokines in patients with metabolic syndrome: a randomized trial. Effects of probiotics on metabolic syndrome. Nutrition 32, 716719.CrossRefGoogle ScholarPubMed
Chao, L, Lihong, C, Xiaohui, W, et al. (2015) Prevention and treatment effect of Saccharomyces boulardii on hyperlipidemia. Academic J Chinese PLA Med Sch 36, 976978, 982.Google Scholar
Davani-Davari, D, Negahdaripour, M, Karimzadeh, I, et al. (2019) Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods 8, 92.CrossRefGoogle ScholarPubMed
Aadahl, M & Jørgensen, T (2003) Validation of a new self-report instrument for measuring physical activity. Med Sci Sports Exerc 35, 11961202.CrossRefGoogle ScholarPubMed
Friedewald, WT, Levy, RI & Fredrickson, DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18, 499502.CrossRefGoogle ScholarPubMed
Tabandeh, MR, Jozaie, S, Ghotbedin, Z, et al. (2022) Dimethyl itaconic acid improves viability and steroidogenesis and suppresses cytokine production in LPS-treated bovine ovarian granulosa cells by regulating TLR4/nfkβ, NLRP3, JNK signaling pathways. Res Vet Sci 152, 8998.CrossRefGoogle ScholarPubMed
Tangerman, A & Nagengast, FM (1996) A gas chromatographic analysis of fecal short-chain fatty acids, using the direct injection method. Anal Biochem 236, 18.CrossRefGoogle ScholarPubMed
Sakpal, TV (2010) Sample size estimation in clinical trial. Perspect Clin Res 1, 67.CrossRefGoogle Scholar
Cicero, AF, Fogacci, F, Bove, M, et al. (2021) Impact of a short-term synbiotic supplementation on metabolic syndrome and systemic inflammation in elderly patients: a randomized placebo-controlled clinical trial. Eur J Nutr 60, 655663.CrossRefGoogle ScholarPubMed
Davoodvandi, A, Marzban, H, Goleij, P, et al. (2021) Effects of therapeutic probiotics on modulation of microRNAs. Cell Commun Signaling 19, 122.CrossRefGoogle ScholarPubMed
Zhao, H, Zhao, C, Dong, Y, et al. (2015) Inhibition of miR122a by lactobacillus rhamnosus GG culture supernatant increases intestinal occludin expression and protects mice from alcoholic liver disease. Toxicol Lett 234, 194200.CrossRefGoogle ScholarPubMed
Rodríguez-Nogales, A, Algieri, F, Garrido-Mesa, J, et al. (2017) Differential intestinal anti-inflammatory effects of Lactobacillus fermentum and Lactobacillus salivarius in DSS mouse colitis: impact on microRNAs expression and microbiota composition. Mol Nutr Food Res 61, 1700144.CrossRefGoogle ScholarPubMed
Ceccarelli, G, Fratino, M, Selvaggi, C, et al. (2017) A pilot study on the effects of probiotic supplementation on neuropsychological performance and micro RNA-29a-c levels in antiretroviral-treated HIV-1-infected patients. Brain Behav 7, e00756.CrossRefGoogle Scholar
Kim, SH, Kim, GJ, Umemura, T, et al. (2017) Aberrant expression of plasma microRNA-33a in an atherosclerosis-risk group. Mol Biol Rep 44, 7988.CrossRefGoogle Scholar
Simionescu, N, Niculescu, LS, Sanda, GM, et al. (2014) Analysis of circulating microRNAs that are specifically increased in hyperlipidemic and/or hyperglycemic sera. Mol Biol Rep 41, 57655773.CrossRefGoogle ScholarPubMed
Alvarez, ML, Khosroheidari, M, Eddy, E, et al. (2015) MicroRNA-27a decreases the level and efficiency of the LDL receptor and contributes to the dysregulation of cholesterol homeostasis. Atherosclerosis 242, 595604.CrossRefGoogle Scholar
Salamat, S, Tabandeh, MR, Jahan-Mihan, A, et al. (2024) The effect of supplementation with a multi-species synbiotic on serum lipid profile, abundance of beneficial gut bacteria and firmicutes to bacteroidetes ratio in patients with dyslipidemia; a randomized, double-blind, placebo-controlled, clinical trial. PharmaNutrition 27, 100367.CrossRefGoogle Scholar
Ambrozkiewicz, F, Karczmarski, J, Kulecka, M, et al. (2020) In search for interplay between stool microRNAs, microbiota and short chain fatty acids in Crohn’s disease-a preliminary study. BMC Gastroenterol 20, 118.CrossRefGoogle ScholarPubMed
Peng, J, Xiao, X, Hu, M, et al. (2018) Interaction between gut microbiome and cardiovascular disease. Life Sci 214, 153157.CrossRefGoogle ScholarPubMed
He, J, Zhang, P, Shen, L, et al. (2020) Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism. Int J Mol Sci 21, 6356.CrossRefGoogle ScholarPubMed
Popeijus, HE, Zwaan, W, Tayyeb, JZ, et al. (2021) Potential contribution of short chain fatty acids to hepatic apolipoprotein AI production. Int J Mol Sci 22, 5986.CrossRefGoogle Scholar
Salamat, S, Jahan-Mihan, A, Tabandeh, MR, et al. (2024) Randomized clinical trial evaluating the efficacy of synbiotic supplementation on serum endotoxin and trimethylamine N-oxide levels in patients with dyslipidaemia. Arch Med Sci–Atherosclerotic Dis 9, 1825.CrossRefGoogle ScholarPubMed
Liou, L & Kaptoge, S (2020) Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: a systematic review and meta-analysis. PloS one 15, e0241993.CrossRefGoogle ScholarPubMed
Behbodikhah, J, Ahmed, S, Elyasi, A, et al. (2021) Apolipoprotein B and cardiovascular disease: biomarker and potential therapeutic target. Metabolites 11, 690.CrossRefGoogle ScholarPubMed
Tajabadi-Ebrahimi, M, Sharifi, N, Farrokhian, A, et al. (2016) 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, 2127.Google ScholarPubMed
Rajkumar, H, Kumar, M, Das, N, et al. (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, 289298.CrossRefGoogle ScholarPubMed
Shakeri, H, Hadaegh, H, Abedi, F, et al. (2014) Consumption of synbiotic bread decreases triacylglycerol and VLDL levels while increasing HDL levels in serum from patients with type-2 diabetes. Lipids 49, 695701.CrossRefGoogle ScholarPubMed