A Review on the Application of Probiotics in Atherosclerosis Management: Evidence from Preclinical Clinical and Animal Studies
Resumo
Atherosclerosis is a chronic vascular disorder characterized by persistent inflammation and the accumulation of atheromatous plaques within the arterial walls, representing a major risk factor for cardiovascular diseases. Emerging evidence suggests that alterations in gut microbiota may influence inflammatory pathways and contribute to the progression of atherosclerosis. This review critically examines the impact of probiotics on atherosclerosis, drawing insights from both preclinical (cellular and animal) and clinical studies. A comprehensive literature search was conducted for studies published between 2010 and 2025 in leading databases, including PubMed, Scopus, Web of Science, Google Scholar, and the Islamic World Science Citation Center (ISC). The search strategy employed a combination of keywords related to “probiotics” and “atherosclerosis.” After removing duplicate entries, titles and abstracts were independently screened, and eligible studies were selected according to predefined inclusion criteria. The final selection focused on evidence regarding the effects of probiotics on atherosclerotic processes. Evidence from cellular, animal, and human studies indicates that probiotic strains such as Lactobacillus spp., Bifidobacterium spp., Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus curvatus, and Akkermansia muciniphila can effectively reduce total cholesterol and LDL levels, increase HDL concentrations, improve endothelial function, and decrease atherosclerotic plaque burden. These benefits are associated with reduced inflammatory markers (IL-6, TNF-α), decreased TMA/TMAO production, inhibition of NF-κB signaling, and modulation of gut microbiota composition. Multi-strain formulations, including Lab4P and VSL#3, not only improve lipid profiles but also enhance plaque stability and reduce foam cell formation. Additionally, the production of beneficial microbial metabolites, such as short-chain fatty acids (SCFAs) and bile acids, along with regulation of cholesterol metabolic pathways, contributes significantly to the anti-atherosclerotic effects of probiotics. By modulating gut microbiota composition as well as metabolic and inflammatory pathways, probiotics demonstrate significant potential to reduce atherosclerotic plaque burden and associated inflammation. These findings support their role as a promising adjunctive strategy for the prevention and management of atherosclerosis.
Palavras-chave
Referências
ABDI, M.; GHALEH, H.E.; RANJBAR, R. Lactobacilli and Bifidobacterium as anti-atherosclerotic agents. Iran Journal of Basic Medical Sciences, v.25, n.8, p.934, 2022.
AHN, H.Y.; KIM, M.; CHAE, J.S.; AHN, Y.T.; SIM, J.H.; CHOI, I.D.; LEE, S.H.; LEE, J.H. Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein AV levels in non-diabetic subjects with hypertriglyceridemia. Atherosclerosis, v.241, n.2, p.649-656, 2015.
ALINEZHAD, B.; KAREGAR, H.K. On-line Thévenin impedance estimation based on PMU data and phase drift correction. IEEE Transactions on Smart Grid, v.9, n.2, p.1033-1042, 2016.
ALINEZHAD, B.; KAREGAR, H.K. Out-of-step protection based on equal area criterion. IEEE Transactions on Power Systems, v.32, n.2, p.968-977, 2016.
ALINEZHAD, B.; KAREGAR, H.K. Predictive out-of-step relay based on equal area criterion and PMU data. International Transactions on Electrical Energy Systems, v.27, n.7, p.e2327, 2017.
BARTON, M. Mechanisms and therapy of atherosclerosis and its clinical complications. Current Opinion in Pharmacology, v.13, n.2, p.149-153, 2013.
BJÖRKEGREN, J.L.; LUSIS, A.J. Atherosclerosis: recent developments. Cell, v.185, n.10, p.1630-1645, 2022.
BOMBA, A.; BRANDEBUROVÁ, A.; RIČANYOVÁ, J.; STROJNÝ, L.; CHMELÁROVÁ, A.; SZABADOSOVÁ, V.; PRAMUKOVÁ, B.; ŽOFČÁKOVÁ, J.; SALAJ, R.; SUPUKOVÁ, A.; ČOKÁŠOVÁ, D. The role of probiotics and natural bioactive compounds in modulation of the common molecular pathways in pathogenesis of atherosclerosis and cancer. Biologia, v.67, n.1, p.1-3, 2012.
CAESAR, R.; FÅK, F.; BÄCKHED, F. Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. Journal of Internal Medicine, v.268, n.4, p.320-328, 2010.
CHAN, Y.K.; EL-NEZAMI, H.; CHEN, Y.; KINNUNEN, K.; KIRJAVAINEN, P.V. Probiotic mixture VSL#3 reduce high fat diet induced vascular inflammation and atherosclerosis in ApoE−/− mice. AMB Express, v.6, n.1, p.61, 2016.
CHARO, I.F.; TAUB, R. Anti-inflammatory therapeutics for the treatment of atherosclerosis. Nature Reviews Drug Discovery, v.10, n.5, p.365-376, 2011.
CHEN, L.; LIU, W.; LI, Y.; LUO, S.; LIU, Q.; ZHONG, Y.; JIAN, Z.; BAO, M. Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process. International Immunopharmacology, v.17, n.1, p.108-115, 2013.
CRUZ NETO, J.P.; DE LUNA FREIRE, M.O.; DE ALBUQUERQUE LEMOS, D.E.; RIBEIRO ALVES, R.M.; DE FARIAS CARDOSO, E.F.; DE MOURA BALARINI, C.; DUMAN, H.; KARAV, S.; DE SOUZA, E.L.; DE BRITO ALVES, J.L. Targeting gut microbiota with probiotics and phenolic compounds in the treatment of atherosclerosis: A comprehensive review. Foods, v.13, n.18, p.2886, 2024.
DABBAGHZADEH A, GHAFFARI J, MORADI S, SAYADIAN SEPARGHAN D. Probiotics on chronic urticaria: A randomized clinical trial study. Caspian J Intern Med14 (2) :192-198.2023.
DIN, A.U.; HASSAN, A.; ZHU, Y.; YIN, T.; GREGERSEN, H.; WANG, G. Amelioration of TMAO through probiotics and its potential role in atherosclerosis. Applied Microbiology and Biotechnology, v.103, n.23, p.9217-9228, 2019.
DING, Y.H.; QIAN, L.Y.; PANG, J.; LIN, J.Y.; XU, Q.; WANG, L.H.; HUANG, D.S.; ZOU, H. The regulation of immune cells by Lactobacilli: a potential therapeutic target for anti-atherosclerosis therapy. Oncotarget, v.8, n.35, p.59915-59929, 2017.
EL HAGE, R.; AL-ARAWÉ, N.; HINTERSEHER, I. The role of the gut microbiome and trimethylamine oxide in atherosclerosis and age-related disease. International Journal of Molecular Sciences, v.24, n.3, p.2399, 2023.
FAN, J.; WATANABE, T. Atherosclerosis: known and unknown. Pathology International, v.72, n.3, p.151-160, 2022.
FANG, Y.; CHEN, H.Q.; ZHANG, X.; ZHANG, H.; XIA, J.; DING, K.; FANG, Z.Y. Probiotic administration of Lactobacillus rhamnosus GR-1 attenuates atherosclerotic plaque formation in ApoE−/− mice fed with a high-fat diet. European Review for Medical and Pharmacological Sciences, v.23, n.8, p.649-656, 2019.
HASANI, A.; EBRAHIMZADEH, S.; HEMMATI, F.; KHABBAZ, A.; HASANI, A.; GHOLIZADEH, P. The role of Akkermansia muciniphila in obesity, diabetes and atherosclerosis. Journal of Medical Microbiology, v.70, n.10, p.001435, 2021.
HASSAN, A.; DIN, A.U.; ZHU, Y.; ZHANG, K.; LI, T.; WANG, Y.; LUO, Y.; WANG, G. Updates in understanding the hypocholesterolemia effect of probiotics on atherosclerosis. Applied Microbiology and Biotechnology, v.103, n.15, p.5993-6006, 2019.
HASSAN, A.; DIN, A.U.; ZHU, Y.; ZHANG, K.; LI, T.; WANG, Y.; XU, S.; LEI, H.; YU, X.; WANG, G. Anti-atherosclerotic effects of Lactobacillus plantarum ATCC 14917 in ApoE−/− mice through modulation of proinflammatory cytokines and oxidative stress. Applied Microbiology and Biotechnology, v.104, n.14, p.6337-6350, 2020.
HEMMATI R, MOHSENZADEHY, SALAMNIA S, SAYEHMIRI F. Early Repolarization and the Severity of Coronary Artery Disease: A Case-control Study. Caspian J Intern Med.12 (4) :526-532.2021.
JEBARI-BENSLAIMAN, S.; GALICIA-GARCÍA, U.; LARREA-SEBAL, A.; OLAETXEA, J.R.; ALLOZA, I.; VANDENBROECK, K.; BENITO-VICENTE, A.; MARTÍN, C. Pathophysiology of atherosclerosis. International Journal of Molecular Sciences, v.23, n.6, p.3346, 2022.
KHALILI, L.; CENTNER, A.M.; SALAZAR, G. Effects of berries, phytochemicals, and probiotics on atherosclerosis through gut microbiota modification: a meta-analysis of animal studies. International Journal of Molecular Sciences, v.24, n.4, p.3084, 2023.
LIANG, X.; ZHANG, Z.; LV, Y.; TONG, L.; LIU, T.; YI, H.; ZHOU, X.; YU, Z.; TIAN, X.; CUI, Q.; YANG, J. Reduction of intestinal trimethylamine by probiotics ameliorated lipid metabolic disorders associated with atherosclerosis. Nutrition, v.79, p.110941, 2020.
LIU, S.; ZHAO, W.; LIU, X.; CHENG, L. Metagenomic analysis of the gut microbiome in atherosclerosis patients identify cross-cohort microbial signatures and potential therapeutic target. FASEB Journal, v.34, n.11, p.14166-14181, 2020.
MAHDAVI-ROSHAN, M.; SALARI, A.; KHEIRKHAH, J.; GHORBANI, Z. The effects of probiotics on inflammation, endothelial dysfunction, and atherosclerosis progression: a mechanistic overview. Heart, Lung and Circulation, v.31, n.5, p.e45-e71, 2022.
MIZOGUCHI, T.; KASAHARA, K.; YAMASHITA, T.; SASAKI, N.; YODOI, K.; MATSUMOTO, T.; EMOTO, T.; HAYASHI, T.; KITANO, N.; YOSHIDA, N.; AMIN, H.Z. Oral administration of the lactic acid bacterium Pediococcus acidilactici attenuates atherosclerosis in mice by inducing tolerogenic dendritic cells. Heart Vessels, v.32, n.6, p.768-776, 2017.
MOLUDI, J.; ALIZADEH, M.; YAGIN, N.L.; PASDAR, Y.; NACHVAK, S.M.; ABDOLLAHZA, D.; TABAEI, A.S. New insights on atherosclerosis: A cross-talk between endocannabinoid systems with gut microbiota. Journal of Cardiovascular and Thoracic Research, v.10, n.3, p.129, 2018.
NABI, X.H.; MA, C.Y.; MANAER, T.; HEIZATI, M.; WULAZIBIEKE, B.; AIERKEN, L. Anti-atherosclerotic effect of traditional fermented cheese whey in atherosclerotic rabbits and identification of probiotics. BMC Complementary and Alternative Medicine, v.16, n.1, p.309, 2016.
O’MORAIN, V.L.; CHEN, J.; PLUMMER, S.F.; MICHAEL, D.R.; RAMJI, D.P. Anti-atherogenic actions of the Lab4b consortium of probiotics in vitro. International Journal of Molecular Sciences, v.24, n.4, p.3639, 2023.
O'MORAIN, V.L.; CHAN, Y.H.; WILLIAMS, J.O.; ALOTIBI, R.; ALAHMADI, A.; RODRIGUES, N.P.; PLUMMER, S.F.; HUGHES, T.R.; MICHAEL, D.R.; RAMJI, D.P. The Lab4P Consortium of Probiotics attenuates atherosclerosis in LDL receptor deficient mice fed a high fat diet and causes plaque stabilization by inhibiting inflammation and several pro-atherogenic processes. Molecular Nutrition & Food Research, v.65, n.17, p.2100214, 2021.
O'MORAIN, V.L.; RAMJI, D.P. The potential of probiotics in the prevention and treatment of atherosclerosis. Molecular Nutrition & Food Research, v.64, n.4, p.1900797, 2020.
OYNOTKINOVA, O.S.; NIKONOV, E.L.; DEMIDOVA, T.Y.; BARANOV, A.P.; KRYUKOV, E.V.; DEDOV, E.I.; KARAVASHKINA, E.A. Changes in the intestinal microbiota as a risk factor for dyslipidemia, atherosclerosis and the role of probiotics in their prevention. Terapevticheskii Arkhiv, v.92, n.9, p.94-101, 2020.
RICCIONI, G.; SBLENDORIO, V. Atherosclerosis: from biology to pharmacological treatment. Journal of Geriatric Cardiology, v.9, n.3, p.305, 2012.
RITZ, K.; DENSWIL, N.P.; STAM, O.C.; VAN LIESHOUT, J.J.; DAEMEN, M.J. Cause and mechanisms of intracranial atherosclerosis. Circulation, v.130, n.16, p.1407-1414, 2014.
SAKAKURA, K.; NAKANO, M.; OTSUKA, F.; LADICH, E.; KOLODGIE, F.D.; VIRMANI, R. Pathophysiology of atherosclerosis plaque progression. Heart, Lung and Circulation, v.22, n.6, p.399-411, 2013.
SOCCOL, C.R.; VANDENBERGHE, L.P.S.; SPIER, M.; MEDEIROS, A.B.P.; YAMAGUISHI, C.T.; LINDNER, J.D.; PANDEY, A.; THOMAZ-SOCCOL, V. The potential of probiotics: a review. [s.l.], p.413-434, 2010.
VOURAKIS, M.; MAYER, G.; ROUSSEAU, G. The role of gut microbiota on cholesterol metabolism in atherosclerosis. International Journal of Molecular Sciences, v.22, n.15, p.8074, 2021.
WILLIAMS, N.T. Probiotics. American Journal of Health-System Pharmacy, v.67, n.6, p.449-458, 2010.
WU, H.; CHIOU, J. Potential benefits of probiotics and prebiotics for coronary heart disease and stroke. Nutrients, v.13, n.8, p.2878, 2021.
ZHAI, T.; REN, W.; WANG, P.; ZHENG, L. Lactobacillus rhamnosus GG protects against atherosclerosis by improving ketone body synthesis. Applied Microbiology and Biotechnology, v.106, n.24, p.8233-8243, 2022.
ZHAI, T.; WANG, P.; HU, X.; ZHENG, L. Probiotics bring new hope for atherosclerosis prevention and treatment. Oxidative Medicine and Cellular Longevity, v.2022, p.3900835, 2022.
This is an open-access article distributed under the terms of the Creative Commons Attribution License
Apontamentos
- Não há apontamentos.
Visitas