Effects of probiotic Lactobacillus paracasei TD3 on moderation of cholesterol biosynthesis pathway in rats

Document Type : Original Article


1 Department of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

2 Microbiology Department, Faculty of science, Islamic Azad University, Arak Branch, Arak, Iran

3 Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran


Objective(s): Prevalence of high-fat food consumption, such as fast foods is one of the major causes of hypercholesterolemia, which can lead to cardiovascular diseases. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and cytochrome P450 7A1 (CYP7A1) are two key genes in cholesterol metabolism. Use of probiotics in the diet is a promising approach for modulation of serum lipid. To confirm the modulation of serum lipids by probiotics, in this study, we have examined the efficacy of Lactobacillus paracasei TD3 in improving blood cholesterol levels.
Materials and Methods: 21 male Wistar rats were divided into three groups randomly (n=7). G1: negative control with normal diet, G2: positive control with high-fat diet, G3T: test group with high-fat diet plus supplementation with L. paracasei TD3 (1010 CFU). In the 21st day, the rats were anesthetized using chloroform and then sacrificed. Blood samples were collected to analyze lipid panel parameters and hepatic enzymes by the auto-analyzer system. Adipose tissue samples were analyzed using real-time PCR for HMGCR and CYP7A1 genes expression.
Results: Consumption of L. paracasei TD3 could reduce serum cholesterol levels significantly (P<0.05); whereas, there was no significant difference between experimental groups for triglycerides, LDL, and HDL levels. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) enzymes were significantly decreased in the probiotic group. Furthermore, expression of HMGCR and CYP7A1 genes was dramatically declined in the probiotic group. There was no significant change in either uric acid or urea between the control and treated groups.
Conclusion: Introduction of L. paracasei TD3 in rat’s diet can modulate serum cholesterol levels.


Main Subjects

1. Mohania D, Kansal VK, Nagpal R, Yamashiro Y, Marotta F. Suppression of diet-induced hypercholesterolemia by probiotic Dahi containing Lactobacillus acidophilus and Lactobacillus plantarum. Int J Probiotics Prebiotics 2013; 8:75-85.
2. Thomas S, Rich MW. Epidemiology, pathophysiology, and prognosis of heart failure in the elderly. Heart Fail Clin 2007; 3:381-387.
3. Gilliland S. Acidophilus milk products: a review of potential benefits to consumers. J Dairy Sci 1989; 72:2483-2494.
4. Manson JE, Tosteson H, Ridker PM, Satterfield S, Hebert P, O’Connor GT, et al. The primary prevention of myocardial infarction. N Engl J Med 1992; 326:1406-1416.
5. Pazzucconi F, Dorigotti F, Gianfranceschi G, Campagnoli G, Sirtori M, Franceschini G, et al. Therapy with HMG CoA reductase inhibitors: characteristics of the long-term permanence of hypocholesterolemic activity. Atherosclerosis 1995; 117:189-198.
6. Eghdamian B, Ghose K. Mode of action and adverse effects of lipid lowering drugs. Drugs Today 1998; 34:943-956.
7.    Godlee F. Adverse effects of statins. Br Med J 2014; 348:3306-3308.
8.    Ooi LG, Liong MT. Cholesterol-lowering effects of probiotics and prebiotics: a review of in vivo and in vitro findings. Int J Mol Sci 2010; 11:2499-2522.
9.    Yoo SR, Kim YJ, Park DY, Jung UJ, Jeon SM, Ahn YT, et al. Probiotics L. plantarum and L. curvatus in combination alter hepatic lipid metabolism and suppress diet‐Induced obesity. Obesity 2013; 21:2571-2578.
10.    Martorell P, Llopis S, González N, Chenoll E, López-Carreras N, Aleixandre A, et al. Probiotic strain Bifidobacterium animalis subsp. lactis CECT 8145 reduces fat content and modulates lipid metabolism and antioxidant response in Caenorhabditis elegans. J Agric Food Chem 2016; 64:3462-3472.
11.    Naito E, Yoshida Y, Makino K, Kounoshi Y, Kunihiro S, Takahashi R, et al. Beneficial effect of oral administration of Lactobacillus casei strain Shirota on insulin resistance in diet-induced obesity mice. J Appl Microbiol 2011; 110:650-657.
12.    Kumar A, Kumar M, Ghosh M, Ganguli A. Modeling in vitro cholesterol reduction in relation to growth of probiotic Lactobacillus casei. Microbiol Immunol 2013; 57:100-110.
13.    Tomaro-Duchesneau C, Jones ML, Shah D, Jain P, Saha S, Prakash S. Cholesterol assimilation by Lactobacillus probiotic Bacteria: An in vitro investigation. Biomed Res Int 2014; 2014:380316-380325.
14. Costabile A, Bergillos T, Rasinkangas P, Korpela K, De Vos W, Gibson GR. Effect of soluble corn fiber with Lactobacillus rhamnosus GG and the pilus-deficient derivative GG-PB12 on fecal microbiota, immune function, and metabolism in healthy elderly (Saimes study). Front Immunol 2017; 8:1443-1456.
15.    Tamtaji OR, Kouchaki E, Salami M, Aghadavod E, Akbari E, Tajabadi-Ebrahimi M, et al. The effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled trial. J Am Coll Nutr 2017; 36:660-665.
16.    Nido SA, Shituleni SA, Mengistu BM, Liu Y, Khan AZ, Gan F, et al. Effects of selenium-enriched probiotics on lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in mice fed a high-fat diet. Biol Trace Elem Res 2016; 171:399-409.
17.    Asemi Z, Samimi M, Tabasi Z, Talebian P, Azarbad Z, Hydarzadeh Z, et al. Effect of daily consumption of probiotic yoghurt on lipid profiles in pregnant women: a randomized controlled clinical trial. J Matern Fetal Neonatal Med 2012; 25:1552-1556.
18.    Samimi M, Dadkhah A, Haddad Kashani H, Tajabadi-Ebrahimi M, Seyed Hosseini E, Asemi Z. The effects of synbiotic supplementation on metabolic status in women with polycystic ovary syndrome: a randomized double-blind clinical trial. Probiotics Antimicrob Proteins 2018:1-7.
19.    Pereira DI, Gibson GR. Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut. Appl Environ Microbiol 2002; 68:4689-4693.
20.    Lye HS, Rusul G, Liong MT. Removal of cholesterol by lactobacilli via incorporation and conversion to coprostanol. J Dairy Sci 2010; 93:1383-1392.
21.    Liong M, Shah N. Acid and bile tolerance and cholesterol removal ability of lactobacilli strains. J Dairy Sci 2005; 88:55-66.
22.    Huang Y, Wang X, Wang J, Wu F, Sui Y, Yang L, et al. Lactobacillus plantarum strains as potential probiotic cultures with cholesterol-lowering activity. J Dairy Sci 2013; 96:2746–2753.
23.    Kullisaar T, Zilmer K, Salum T, Rehema A, Zilmer M. 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 2016; 15:93-99.
24.    Karamali M, Dadkhah F, Sadrkhanlou M, Jamilian M, Ahmadi S, Tajabadi-Ebrahimi M, et al. Effects of probiotic supplementation on glycaemic control and lipid profiles in gestational diabetes: A randomized, double-blind, placebo-controlled trial. Diabetes Metab 2016; 42:234-241.
25.    Mei L, Tang Y, Li M, Yang P, Liu Z, Yuan J, et al. Co-administration of cholesterol-lowering probiotics and anthraquinone from Cassia obtusifolia L. ameliorate non-alcoholic fatty liver. PloS One 2015; 10:138078-138094.
26.    Damodharan K, Lee YS, Palaniyandi SA, Yang SH, Suh J-W. Preliminary probiotic and technological characterization of Pediococcus pentosaceus strain KID7 and in vivo assessment of its cholesterol-lowering activity. Front microbiol 2015; 6:768-782.
27.    Kumar M, Rakesh S, Nagpal R, Hemalatha R, Ramakrishna A, Sudarshan V, et al. Probiotic Lactobacillus rhamnosus GG and Aloe vera gel improve lipid profiles in hypercholesterolemic rats. Nutrition 2013; 29:574-579.
28.    Park YH, Kim JG, Shin YW, Kim SH, Whang KY. Effect of dietary inclusion of Lactobacillus acidophilus ATCC 43121 on cholesterol metabolism in rats. J Microbiol Biotechnol 2007; 17:655-662.
29.    Grunewald K. Serum cholesterol levels in rats fed skim milk fermented by Lactobacillus acidophilus. J Food Sci 1982; 47:2078-2079.
30.    Al-Sheraji SH, Ismail A, Manap MY, Mustafa S, Yusof RM, Hassan FA. Hypocholesterolaemic effect of yoghurt containing Bifidobacterium pseudocatenulatum G4 or Bifidobacterium longum BB536. Food Chem 2012; 135:356-361.
31.    Wu Y, Zhang Q, Ren Y, Ruan Z. Effect of probiotic Lactobacillus on lipid profile: A systematic review and meta-analysis of randomized, controlled trials. PLoS One 2017; 12:178868-178883.
32.    Yadav R, Khan SH, Mada SB, Meena S, Kapila R, Kapila S. Consumption of Probiotic Lactobacillus fermentum MTCC: 5898-fermented milk attenuates dyslipidemia, oxidative stress, and inflammation in male rats fed on cholesterol-enriched diet. Probiotics Antimicrob Proteins 2018:1-10.
33.    Aminlari L, Shekarforoush SS, Hosseinzadeh S, Nazifi S, Sajedianfard J, Eskandari MH. Effect of probiotics Bacillus coagulans and Lactobacillus plantarum on lipid profile and feces bacteria of rats fed cholesterol-enriched diet. Probiotics Antimicrob Proteins 2018:1-9.
34.    Lew LC, Choi SB, Khoo BY, Sreenivasan S, Ong KL, Liong MT. Lactobacillus plantarum DR7 reduces cholesterol via phosphorylation of AMPK that down-regulated the mRNA expression of HMG-CoA reductase. Korean J  Food Sci Anim Resour 2018; 38:350-361.