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ISSN (Online): 2211-551X

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Unleashing the Potential of Gut Microbiota: Cholesterol Reduction Through Microbial Bile Acid Metabolism

Author(s): Nazia Nazrul Nafsi, Md. Ashiqur Rahman, Md. Asaduzzaman Shishir, Md. Shamsul Arefin, Jinath Sultana Jime, Nayeema Bulbul, Ashrafus Safa and Md. Fakruddin*

Volume 13, Issue 1, 2024

Published on: 08 March, 2024

Page: [6 - 14] Pages: 9

DOI: 10.2174/0122115501282536240301055402

Price: $65

Abstract

Cholesterol metabolism is a crucial mechanism for preserving cellular functionality, and overall human health. Cardiovascular diseases and other conditions can arise due to dysregulation of cholesterol levels. Bile acids’ enterohepatic circulation greatly influences cholesterol homeostasis. Recent research has emphasized the essential role of the gut microbiota in bile acid metabolism and its association with cholesterol regulation. Living microbial supplements known as probiotics have been studied as a potential means of reducing cholesterol by modifying the gut microbiome. This review explores existing theories of how probiotic production and modification of bile acids affect cholesterol metabolism. Discussion ensues regarding the processes by which probiotics lower cholesterol, including bile acid deconjugation, conversion of cholesterol to coprostanol and cholestenone, co-precipitation of cholesterol with deconjugated bile, and disruption of cholesterol micelles by Bile Salt Hydrolase (BSH). According to research, there are significant therapeutic ramifications in understanding the complex interactions between the gut microbiome and host cholesterol metabolism. More research is required to comprehend the causal mechanisms further and produce new methods for lowering microbiota-mediated cholesterol to improve human health.

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[1]
Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013; 40(1): 195-211.
[http://dx.doi.org/10.1016/j.pop.2012.11.003] [PMID: 23402469]
[2]
Li T, Chiang JYL. Regulation of bile acid and cholesterol metabolism by PPARs. PPAR Res 2009; 2009: 1-15.
[http://dx.doi.org/10.1155/2009/501739] [PMID: 19636418]
[3]
Sivamaruthi BS, Fern LA, Rashidah Pg Hj Ismail DSN, Chaiyasut C. The influence of probiotics on bile acids in diseases and aging. Biomed Pharmacother 2020; 128: 110310.
[http://dx.doi.org/10.1016/j.biopha.2020.110310] [PMID: 32504921]
[4]
Vourakis M, Mayer G, Rousseau G. The role of gut microbiota on cholesterol metabolism in atherosclerosis. Int J Mol Sci 2021; 22(15): 8074.
[http://dx.doi.org/10.3390/ijms22158074] [PMID: 34360839]
[5]
Hassan A, Din AU, Zhu Y, et al. Updates in understanding the hypocholesterolemia effect of probiotics on atherosclerosis. Appl Microbiol Biotechnol 2019; 103(15): 5993-6006.
[http://dx.doi.org/10.1007/s00253-019-09927-4] [PMID: 31201452]
[6]
Hotel A. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Joint FAO/WHO Expert Consultation 2001 2014; 1-34.
[7]
Jones ML, Tomaro-Duchesneau C, Martoni CJ, Prakash S. Cholesterol lowering with bile salt hydrolase-active probiotic bacteria, mechanism of action, clinical evidence, and future direction for heart health applications. Expert Opin Biol Ther 2013; 13(5): 631-42.
[http://dx.doi.org/10.1517/14712598.2013.758706] [PMID: 23350815]
[8]
Chiang JYL, Ferrell JM. Bile acid metabolism in liver pathobiology. Gene Expr 2018; 18(2): 71-87.
[http://dx.doi.org/10.3727/105221618X15156018385515] [PMID: 29325602]
[9]
Lambert JM, Bongers RS, de Vos WM, Kleerebezem M. Functional analysis of four bile salt hydrolase and penicillin acylase family members in Lactobacillus plantarum WCFS1. Appl Environ Microbiol 2008; 74(15): 4719-26.
[http://dx.doi.org/10.1128/AEM.00137-08] [PMID: 18539794]
[10]
Long SL, Gahan CGM, Joyce SA. Interactions between gut bacteria and bile in health and disease. Mol Aspects Med 2017; 56: 54-65.
[http://dx.doi.org/10.1016/j.mam.2017.06.002] [PMID: 28602676]
[11]
Javed S, Munir A, Javed GA, Latif Z, Javed S, Arshad N. Genetic diversity, cholesterol reduction, and presence of conserved bile salt hydrolase gene in probiotic strains from human milk. Lett Appl Microbiol 2023; 76(3): ovad024.
[http://dx.doi.org/10.1093/lambio/ovad024] [PMID: 36758963]
[12]
Pereira DIA, Gibson GR. Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut. Appl Environ Microbiol 2002; 68(9): 4689-93.
[http://dx.doi.org/10.1128/AEM.68.9.4689-4693.2002] [PMID: 12200334]
[13]
Liong MT, Shah NP. Effects of a Lactobacillus casei synbiotic on serum lipoprotein, intestinal microflora, and organic acids in rats. J Dairy Sci 2006; 89(5): 1390-9.
[http://dx.doi.org/10.3168/jds.S0022-0302(06)72207-X] [PMID: 16606710]
[14]
Liong MT, Shah NP. Acid and bile tolerance and cholesterol removal ability of lactobacilli strains. J Dairy Sci 2005; 88(1): 55-66.
[http://dx.doi.org/10.3168/jds.S0022-0302(05)72662-X] [PMID: 15591367]
[15]
Lye HS, Rahmat-Ali GR, Liong MT. Mechanisms of cholesterol removal by lactobacilli under conditions that mimic the human gastrointestinal tract. Int Dairy J 2010; 20(3): 169-75.
[http://dx.doi.org/10.1016/j.idairyj.2009.10.003]
[16]
Lye HS, Rusul G, Liong MT. Removal of cholesterol by lactobacilli via incorporation and conversion to coprostanol. J Dairy Sci 2010; 93(4): 1383-92.
[http://dx.doi.org/10.3168/jds.2009-2574] [PMID: 20338415]
[17]
De Preter V, Vanhoutte T, Huys G, et al. Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans. Am J Physiol Gastrointest Liver Physiol 2007; 292(1): G358-68.
[http://dx.doi.org/10.1152/ajpgi.00052.2006] [PMID: 16990449]
[18]
Kolodziejczyk AA, Zheng D, Elinav E. Diet–microbiota interactions and personalized nutrition. Nat Rev Microbiol 2019; 17(12): 742-53.
[http://dx.doi.org/10.1038/s41579-019-0256-8] [PMID: 31541197]
[19]
Singh TP, Natraj BH. Next-generation probiotics: A promising approach towards designing personalized medicine. Crit Rev Microbiol 2021; 47(4): 479-98.
[http://dx.doi.org/10.1080/1040841X.2021.1902940] [PMID: 33822669]
[20]
Jia B, Zou Y, Han X, Bae JW, Jeon CO. Gut microbiome-mediated mechanisms for reducing cholesterol levels: Implications for ameliorating cardiovascular disease. Trends Microbiol 2023; 31(1): 76-91.
[http://dx.doi.org/10.1016/j.tim.2022.08.003] [PMID: 36008191]
[21]
Goldstein JL, Brown MS. A century of cholesterol and coronaries: From plaques to genes to statins. Cell 2015; 161(1): 161-72.
[http://dx.doi.org/10.1016/j.cell.2015.01.036] [PMID: 25815993]
[22]
Di Paolo G, Kim TW. Linking lipids to Alzheimer’s disease: Cholesterol and beyond. Nat Rev Neurosci 2011; 12(5): 284-96.
[http://dx.doi.org/10.1038/nrn3012] [PMID: 21448224]
[23]
Chiang JYL. Bile acid metabolism and signaling in liver disease and therapy. Liver Res 2017; 1(1): 3-9.
[http://dx.doi.org/10.1016/j.livres.2017.05.001] [PMID: 29104811]
[24]
Schwingshackl L, Hoffmann G. Dietary fatty acids in the secondary prevention of coronary heart disease: A systematic review, meta-analysis and meta-regression. BMJ Open 2014; 4(4): e004487.
[http://dx.doi.org/10.1136/bmjopen-2013-004487] [PMID: 24747790]
[25]
Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, Eds. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill Education 2019.
[26]
Mannu GS, Zaman MJ, Gupta A, Rehman HU, Myint PK. Evidence of lifestyle modification in the management of hypercholesterolemia. Curr Cardiol Rev 2013; 9(1): 2-14.
[PMID: 22998604]
[27]
Ridlon JM, Kang DJ, Hylemon PB. Bile salt biotransformations by human intestinal bacteria. J Lipid Res 2006; 47(2): 241-59.
[http://dx.doi.org/10.1194/jlr.R500013-JLR200] [PMID: 16299351]
[28]
Hylemon PB, Zhou H, Pandak WM, Ren S, Gil G, Dent P. Bile acids as regulatory molecules. J Lipid Res 2009; 50(8): 1509-20.
[http://dx.doi.org/10.1194/jlr.R900007-JLR200] [PMID: 19346331]
[29]
Zhang Y, Lee FY, Barrera G, et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci USA 2006; 103(4): 1006-11.
[http://dx.doi.org/10.1073/pnas.0506982103] [PMID: 16410358]
[30]
Li T, Chiang JYL. Bile acids as metabolic regulators. Curr Opin Gastroenterol 2015; 31(2): 159-65.
[http://dx.doi.org/10.1097/MOG.0000000000000156] [PMID: 25584736]
[31]
Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006; 439(7075): 484-9.
[http://dx.doi.org/10.1038/nature04330] [PMID: 16400329]
[32]
Pols TWH, Noriega LG, Nomura M, Auwerx J, Schoonjans K. The bile acid membrane receptor TGR5: A valuable metabolic target. Dig Dis 2011; 29(1): 37-44.
[http://dx.doi.org/10.1159/000324126] [PMID: 21691102]
[33]
Zhu H, Zhao F, Zhang W, et al. Cholesterol-lowering effect of bile salt hydrolase from a Lactobacillus johnsonii strain mediated by FXR pathway regulation. Food Funct 2022; 13(2): 725-36.
[http://dx.doi.org/10.1039/D1FO03143K] [PMID: 34935837]
[34]
Porez G, Prawitt J, Gross B, Staels B. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J Lipid Res 2012; 53(9): 1723-37.
[http://dx.doi.org/10.1194/jlr.R024794] [PMID: 22550135]
[35]
Artem N, Volodymyr C, Vadim S, Lesya G, Nataliya Mo. Modification of gut bacterial bile salt hydrolase activity and cardiovascular risk: A randomized study. USMYJ 2020; 117(3): 1-10.
[36]
Hernández-Gómez JG, López-Bonilla A, Trejo-Tapia G, Ávila-Reyes SV, Jiménez-Aparicio AR, Hernández-Sánchez H. in vitro bile salt hydrolase (BSH) activity screening of different probiotic microorganisms. Foods 2021; 10(3): 674.
[http://dx.doi.org/10.3390/foods10030674] [PMID: 33810002]
[37]
Costabile A, Buttarazzi I, Kolida S, et al. An in vivo assessment of the cholesterol-lowering efficacy of Lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults. PLoS One 2017; 12(12): e0187964.
[http://dx.doi.org/10.1371/journal.pone.0187964] [PMID: 29228000]
[38]
Kumar M, Nagpal R, Kumar R, et al. Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases. Exp Diabetes Res 2012; 2012: 1-14.
[http://dx.doi.org/10.1155/2012/902917] [PMID: 22611376]
[39]
Cohen DE. Balancing cholesterol synthesis and absorption in the gastrointestinal tract. J Clin Lipidol 2008; 2(2): S1-3.
[http://dx.doi.org/10.1016/j.jacl.2008.01.004] [PMID: 19343078]
[40]
Juste C, Gérard P. Cholesterol-to-coprostanol conversion by the gut microbiota: What we know, suspect, and ignore. Microorganisms 2021; 9(9): 1881.
[http://dx.doi.org/10.3390/microorganisms9091881] [PMID: 34576776]
[41]
Joyce SA, Shanahan F, Hill C, Gahan CGM. Bacterial bile salt hydrolase in host metabolism: Potential for influencing gastrointestinal microbe-host crosstalk. Gut Microbes 2014; 5(5): 669-74.
[http://dx.doi.org/10.4161/19490976.2014.969986] [PMID: 25483337]
[42]
Chiang JY. Bile acid metabolism and signaling. Compr Physiol 2013; 3(3): 1191-212.
[http://dx.doi.org/10.1002/cphy.c120023] [PMID: 23897684]
[43]
Dawson PA, Shneider BL, Hofmann AF. CHAPTER 56 - Bile formation and the enterohepatic circulation. In: Johnson LR, Ed. Physiology of the Gastrointestinal Tract. (4th ed.). Burlington: Academic Press 2006; pp. 1437-62.
[http://dx.doi.org/10.1016/B978-012088394-3/50059-3]
[44]
Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol 2014; 30(3): 332-8.
[http://dx.doi.org/10.1097/MOG.0000000000000057] [PMID: 24625896]
[45]
Jones ML, Martoni CJ, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: A randomized controlled trial. Eur J Clin Nutr 2012; 66(11): 1234-41.
[http://dx.doi.org/10.1038/ejcn.2012.126] [PMID: 22990854]
[46]
Hofmann AF, Hagey LR. Bile acids: Chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci 2008; 65(16): 2461-83.
[http://dx.doi.org/10.1007/s00018-008-7568-6] [PMID: 18488143]
[47]
Monte MJ, Marin JJG, Antelo A, Vazquez-Tato J. Bile acids: Chemistry, physiology, and pathophysiology. World J Gastroenterol 2009; 15(7): 804-16.
[http://dx.doi.org/10.3748/wjg.15.804] [PMID: 19230041]
[48]
Begley M, Gahan CGM, Hill C. The interaction between bacteria and bile. FEMS Microbiol Rev 2005; 29(4): 625-51.
[http://dx.doi.org/10.1016/j.femsre.2004.09.003] [PMID: 16102595]
[49]
Sayin SI, Wahlström A, Felin J, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013; 17(2): 225-35.
[http://dx.doi.org/10.1016/j.cmet.2013.01.003] [PMID: 23395169]
[50]
Rosenfeld RS, Fukushima DK, Hellman L, Gallagher TF. The transformation of cholesterol to coprostanol. J Biol Chem 1954; 211(1): 301-11.
[http://dx.doi.org/10.1016/S0021-9258(18)71221-0] [PMID: 13211667]
[51]
Li L, Batt SM, Wannemuehler M, Dispirito A, Beitz DC. Effect of feeding of a cholesterol-reducing bacterium, Eubacterium coprostanoligenes, to germ-free mice. Lab Anim Sci 1998; 48(3): 253-5.
[PMID: 10090024]
[52]
Li L, Baumann CA, Meling DD, Sell JL, Beitz DC. Effect of orally administered Eubacterium coprostanoligenes ATCC 51222 on plasma cholesterol concentration in laying hens. Poult Sci 1996; 75(6): 743-5.
[http://dx.doi.org/10.3382/ps.0750743] [PMID: 8737839]
[53]
Li L, Buhman KK, Hartman PA, Beitz DC. Hypocholesterolemic effect of Eubacterium coprostanoligenes ATCC 51222 in rabbits. Lett Appl Microbiol 1995; 20(3): 137-40.
[http://dx.doi.org/10.1111/j.1472-765X.1995.tb00410.x] [PMID: 7766068]
[54]
Kreit J. Microbial catabolism of sterols: Focus on the enzymes that transform the sterol 3β-hydroxy-5-en into 3-keto-4-en. FEMS Microbiol Lett 2017; 364(3): fnx007.
[http://dx.doi.org/10.1093/femsle/fnx007] [PMID: 28087615]
[55]
Zanotti I, Turroni F, Piemontese A, et al. Evidence for cholesterol-lowering activity by Bifidobacterium bifidum PRL2010 through gut microbiota modulation. Appl Microbiol Biotechnol 2015; 99(16): 6813-29.
[http://dx.doi.org/10.1007/s00253-015-6564-7] [PMID: 25863679]
[56]
Ren D, Li L, Schwabacher AW, Young JW, Beitz DC. Mechanism of cholesterol reduction to coprostanol by Eubacterium coprostanoligenes ATCC 51222. Steroids 1996; 61(1): 33-40.
[http://dx.doi.org/10.1016/0039-128X(95)00173-N] [PMID: 8789734]
[57]
Gérard P, Lepercq P, Leclerc M, Gavini F, Raibaud P, Juste C. Bacteroides sp. strain D8, the first cholesterol-reducing bacterium isolated from human feces. Appl Environ Microbiol 2007; 73(18): 5742-9.
[http://dx.doi.org/10.1128/AEM.02806-06] [PMID: 17616613]
[58]
Kenny DJ, Plichta DR, Shungin D, Koppel N, Hall AB, Fu B, et al. Cholesterol metabolism by uncultured human gut bacteria influences host cholesterol level. Cell Host Microbe 2020; 28(2): 245-57.
[http://dx.doi.org/10.1016/j.chom.2020.05.013]
[59]
Bustos AY, Font de Valdez G, Fadda S, Taranto MP. New insights into bacterial bile resistance mechanisms: the role of bile salt hydrolase and its impact on human health. Food Res Int 2018; 112: 250-62.
[http://dx.doi.org/10.1016/j.foodres.2018.06.035] [PMID: 30131136]
[60]
Song Z, Cai Y, Lao X, et al. Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome. Microbiome 2019; 7(1): 9.
[http://dx.doi.org/10.1186/s40168-019-0628-3] [PMID: 30674356]
[61]
Li Y, Hou H, Wang X, et al. Diammonium glycyrrhizinate ameliorates obesity through modulation of gut microbiota-conjugated BAs-FXR signaling. Front Pharmacol 2021; 12: 796590.
[http://dx.doi.org/10.3389/fphar.2021.796590] [PMID: 34992541]
[62]
Begley M, Hill C, Gahan CGM. Bile salt hydrolase activity in probiotics. Appl Environ Microbiol 2006; 72(3): 1729-38.
[http://dx.doi.org/10.1128/AEM.72.3.1729-1738.2006] [PMID: 16517616]
[63]
Kriaa A, Bourgin M, Potiron A, et al. Microbial impact on cholesterol and bile acid metabolism: current status and future prospects. J Lipid Res 2019; 60(2): 323-32.
[http://dx.doi.org/10.1194/jlr.R088989] [PMID: 30487175]
[64]
Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 2016; 7(3): 189-200.
[http://dx.doi.org/10.1080/19490976.2015.1134082] [PMID: 26963409]
[65]
St-Onge MP, Farnworth ER, Jones PJH. Consumption of fermented and nonfermented dairy products: Effects on cholesterol concentrations and metabolism. Am J Clin Nutr 2000; 71(3): 674-81.
[http://dx.doi.org/10.1093/ajcn/71.3.674] [PMID: 10702159]
[66]
Nazir Y, Hussain SA, Abdul Hamid A, Song Y. Probiotics and their potential preventive and therapeutic role for cancer, high serum cholesterol, and allergic and HIV diseases. BioMed Res Int 2018; 2018: 1-17.
[http://dx.doi.org/10.1155/2018/3428437] [PMID: 30246019]
[67]
Quigley EMM. Prebiotics and probiotics in digestive health. Clin Gastroenterol Hepatol 2019; 17(2): 333-44.
[http://dx.doi.org/10.1016/j.cgh.2018.09.028] [PMID: 30267869]
[68]
Zhai T, Wang P, Hu X, Zheng L. Probiotics bring new hope for atherosclerosis prevention and treatment. Oxid Med Cell Longev 2022; 2022: 1-13.
[http://dx.doi.org/10.1155/2022/3900835] [PMID: 36193065]
[69]
Zhang QQ, Lu LG. Nonalcoholic fatty liver disease: Dyslipidemia, risk for cardiovascular complications, and treatment strategy. J Clin Transl Hepatol 2015; 3(1): 78-84.
[http://dx.doi.org/10.14218/JCTH.2014.00037] [PMID: 26357637]
[70]
Kumari M, Singh P, Nataraj BH, et al. Fostering next-generation probiotics in human gut by targeted dietary modulation: An emerging perspective. Food Res Int 2021; 150(Pt A): 110716.
[http://dx.doi.org/10.1016/j.foodres.2021.110716] [PMID: 34865747]
[71]
Adebola OO, Corcoran O, Morgan WA. Prebiotics may alter bile salt hydrolase activity: Possible implications for cholesterol metabolism. PharmaNutrition 2020; 12: 100182.
[http://dx.doi.org/10.1016/j.phanu.2020.100182]
[72]
Davani-Davari D, Negahdaripour M, Karimzadeh I, et al. Prebiotics: Definition, types, sources, mechanisms, and clinical applications. Foods 2019; 8(3): 92.
[http://dx.doi.org/10.3390/foods8030092] [PMID: 30857316]
[73]
López-Moreno A, Suárez A, Avanzi C, Monteoliva-Sánchez M, Aguilera M. Probiotic strains and intervention total doses for modulating obesity-related microbiota dysbiosis: A systematic review and meta-analysis. Nutrients 2020; 12(7): 1921.
[http://dx.doi.org/10.3390/nu12071921] [PMID: 32610476]
[74]
Bubnov RV, Babenko LP, Lazarenko LM, et al. Comparative study of probiotic effects of Lactobacillus and Bifidobacteria strains on cholesterol levels, liver morphology and the gut microbiota in obese mice. EPMA J 2017; 8(4): 357-76.
[http://dx.doi.org/10.1007/s13167-017-0117-3] [PMID: 29209439]
[75]
Culpepper T, Rowe CC, Nieves C, et al. Effect of 3 probiotic strains on bile acids and glucose metabolism in healthy adults: A randomized, double-blind placebo-controlled crossover study. FASEB J 2016; 30: 289.6.
[http://dx.doi.org/10.1096/fasebj.30.1_supplement.289.6]

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