Beneficial effects of Enterococcus faecalis in hypercholesterolemic mice on cholesterol transportation and gut microbiota
Hypercholesterolemia plays a critical role in the development of atherosclerosis and cardiovascular diseases. Many works have been reported that gut microbiota could affect hypercholesterolemia through cholesterol metabolism. However, the role of gut microbiota on cholesterol transportation remains unclear. In this study, 8-week-old C57BL/6J mice were fed with high-cholesterol diet to build the hypercholesterolemic mice. Then, the hypercholesterolemic mice got the oral administration of Enterococcus faecalis ATCC19433 at a dose of 109 CFU/mL/day or PBS with high-cholesterol diet for 4 weeks. Serum was collected to detect the concentration of total cholesterol (TC). Meanwhile, pathology, histology, real-time polymerase chain reaction, Western blot, and immunofluorescence were used to evaluate the expression of ABCG5 and ABCG8 in the liver and small intestine. We also analyzed the composition of gut microbiota through high-throughput sequencing method. Oral administration of E. faecalis ATCC19433 significantly decreased the concentration of serum cholesterol in hypercholesterolemic mice. Furthermore, E. faecalis ATCC19433 reduced the concentration of liver cholesterol and improved cholesterol by increasing the expression of ABCG5 and ABCG8. Moreover, oral administration of E. faecalis ATCC19433 modulated the composition of gut microbiota and increased the counts of Lactobacillus, Bifidobacterium, and Akkermansia. Our results showed that E. faecalis ATCC19433 could exert hypocholesterolemic effect on hypercholesterolemic mice by improving transporter ABCG5 and ABCG8. E. faecalis ATCC19433 maybe contribute to the transportation of cholesterol potentially and modulate the composition of gut microbiota.
KeywordsEnterococcus faecalis Cholesterol-lowering effect ABCG5/8 Gut microbiota
This study was supported by grants from the National Natural Science Foundation of China (11572064, 31771599), the National Key Technology R&D Program of China (2016YFC1102305, 2016YFC1101101), and the Fundamental Research Funds for the Central Universities (106112017CDJZRPY0202, 106112017CDJPT230001, 106112017CDJXY230002).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
This article does not contain any studies with human participants performed by any of the authors. All experiments were approved by the Animal Care and Use Committee of Chongqing University (China) according to the Chinese Council on Animal Care guidelines.
- Arellano-Martinez GL, Granados O, Palacios-Gonzalez B, Torres N, Medina-Vera I, Tovar AR (2014) Soya protein stimulates bile acid excretion by the liver and intestine through direct and indirect pathways influenced by the presence of dietary cholesterol. Br J Nutr 111(12):2059–2066. https://doi.org/10.1017/S0007114514000361 CrossRefGoogle Scholar
- Calpe-Berdiel L, Escola-Gil JC, Ribas V, Navarro-Sastre A, Garces-Garces J, Blanco-Vaca F (2005) Changes in intestinal and liver global gene expression in response to a phytosterol-enriched diet. Atherosclerosis 181(1):75–85. https://doi.org/10.1016/j.Atherosclerosis.2004.11.025 CrossRefGoogle Scholar
- Cavallini DC, Bedani R, Bomdespacho LQ, Vendramini RC, Rossi EA (2009) Effects of probiotic bacteria, isoflavones and simvastatin on lipid profile and atherosclerosis in cholesterol-fed rabbits: a randomized double-blind study. Lipids Health Dis 8(1):1. https://doi.org/10.1186/1476-511X-8-1 CrossRefGoogle Scholar
- De Beer MC, Wroblewski JM, Noffsinger VP, Rateri DL, Howatt DA, Balakrishnan A, Ji A, Shridas P, Thompson JC, van der Westhuyzen DR, Tannock LR, Daugherty A, Webb NR, De Beer FC (2014) Deficiency of endogenous acute phase serum amyloid A does not affect atherosclerotic lesions in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 34(2):255–261. https://doi.org/10.1161/ATVBAHA.113.302247 CrossRefGoogle Scholar
- Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Neyrinck AM, Possemiers S, Van Holle A, Francois P, de Vos WM, Delzenne NM, Schrenzel J, Cani PD (2011) Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60(11):2775–2786. https://doi.org/10.2337/db11-0227 CrossRefGoogle Scholar
- Gilliland SE, Nelson CR, Maxwell C (1985) Assimilation of cholesterol by Lactobacillus acidophilus. Appl Environ Microbiol 49(2):377–381Google Scholar
- Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME (2014) Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11(8):506–514. https://doi.org/10.1038/nrgastro.2014.66 CrossRefGoogle Scholar
- Ijaz MU, Ahmed MI, Zou X, Hussain M, Zhang M, Zhao F, Xu X, Zhou G, Li C (2018) Beef, casein, and soy proteins differentially affect lipid metabolism, triglycerides accumulation and gut microbiota of high-fat diet-fed C57BL/6J mice. Front Microbiol 9:2200. https://doi.org/10.3389/fmicb.2018.02200 CrossRefGoogle Scholar
- Kondoh M, Shimada T, Fukada K, Morita M, Katada K, Higashimura Y, Mizushima K, Okamori M, Naito Y, Yoshikawa T (2014) Beneficial effects of heat-treated Enterococcus faecalis FK-23 on high-fat diet-induced hepatic steatosis in mice. Br J Nutr 112(6):868–875. https://doi.org/10.1017/S0007114514001792 CrossRefGoogle Scholar
- Kubeck R, Bonet-Ripoll C, Hoffmann C, Walker A, Muller VM, Schuppel VL, Lagkouvardos I, Scholz B, Engel KH, Daniel H, Schmitt-Kopplin P, Haller D, Clavel T, Klingenspor M (2016) Dietary fat and gut microbiota interactions determine diet-induced obesity in mice. Mol Metab 5(12):1162–1174. https://doi.org/10.1016/j.molmet.2016.10.001 CrossRefGoogle Scholar
- Lopes BP, Gaique TG, Souza LL, Paula GS, Kluck GE, Atella GC, Gomes AC, Simas NK, Kuster RM, Ortiga-Carvalho TM, Pazos-Moura CC, Oliveira KJ (2015) Cinnamon extract improves the body composition and attenuates lipogenic processes in the liver and adipose tissue of rats. Food Funct 6(10):3257–3265. https://doi.org/10.1039/c5fo00569h CrossRefGoogle Scholar
- Lu K, Lee MH, Yu H, Zhou Y, Sandell SA, Salen G, Patel SB (2002) Molecular cloning, genomic organization, genetic variations, and characterization of murine sterolin genes Abcg5 and Abcg8. J Lipid Res 43(4):565–578Google Scholar
- Martinez I, Wallace G, Zhang C, Legge R, Benson AK, Carr TP, Moriyama EN, Walter J (2009) Diet-induced metabolic improvements in a hamster model of hypercholesterolemia are strongly linked to alterations of the gut microbiota. Appl Environ Microbiol 75(12):4175–4184. https://doi.org/10.1128/AEM.00380-09 CrossRefGoogle Scholar
- Nunes VS, Leanca CC, Panzoldo NB, Parra E, Cazita PM, Nakandakare ER, de Faria EC, Quintao EC (2011) HDL-C concentration is related to markers of absorption and of cholesterol synthesis: study in subjects with low vs. high HDL-C. Clin Chim Acta, Int J Clin Chem 412(1–2):176–180. https://doi.org/10.1016/j.cca.2010.09.039 CrossRefGoogle Scholar
- Park YH, Kim JG, Shin YW, Kim SH, Whang KY (2007) Effect of dietary inclusion of Lactobacillus acidophilus ATCC 43121 on cholesterol metabolism in rats. J Microbiol Biotechnol 17(4):655–662Google Scholar
- Slatis K, Gafvels M, Kannisto K, Ovchinnikova O, Paulsson-Berne G, Parini P, Jiang ZY, Eggertsen G (2010) Abolished synthesis of cholic acid reduces atherosclerotic development in apolipoprotein E knockout mice. J Lipid Res 51(11):3289–3298. https://doi.org/10.1194/jlr.M009308 CrossRefGoogle Scholar
- Tryndyak VP, Han T, Muskhelishvili L, Fuscoe JC, Ross SA, Beland FA, Pogribny IP (2011) Coupling global methylation and gene expression profiles reveal key pathophysiological events in liver injury induced by a methyl-deficient diet. Mol Nutr Food Res 55(3):411–418. https://doi.org/10.1002/mnfr.201000300 CrossRefGoogle Scholar
- Wang Y, Xu N, Xi A, Ahmed Z, Zhang B, Bai X (2009) Effects of Lactobacillus Plantarum MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high-cholesterol diet. Appl Microbiol Biotechnol 84(2):341–347. https://doi.org/10.1007/s00253-009-2012-x CrossRefGoogle Scholar
- Wilson MD, Rudel LL (1994) Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. J Lipid Res 35(6):943–955Google Scholar