Abstract
Bifidobacterium longum (B. longum) is a beneficial anaerobic bacteria that may improve cardiovascular disease (CVD). We studied B. longum L556, isolated from healthy human feces, in coronary heart disease (CHD) patients through anaerobic fermentation in vitro. Results showed that B. longum L556 increased Lactobacillus, Faecalibacterium, Prevotella, and Alistipes, while reducing Firmicutes to Bacteroidetes, Eggerthella, Veillonella, Holdemanella, and Erysipelotrichaceae_UCG-003 in the gut microbiota of CHD patients. B. longum L556 also enhanced anti-inflammatory effects by modulating gut microbiota and metabolites like SCFAs. Additionally, it regulated lipid and amino acid metabolism in fermentation metabolites from the CHD group. These findings suggest that B. longum L556 has potential for improving CHD by modulating the intestinal microbiota, promoting SCFA production, and regulating lipid metabolism and inflammation.
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References
Alard J, Lehrter V, Rhimi M, Mangin I, Peucelle V, Abraham AL, Mariadassou M et al (2016) Beneficial metabolic effects of selected probiotics on diet-induced obesity and insulin resistance in mice are associated with improvement of dysbiotic gut microbiota. Environ Microbiol 18(5):1484–1497. https://doi.org/10.1111/1462-2920.13181
Wirtz PH, von Kanel R (2017) Psychological stress, inflammation, and coronary heart disease. Curr Cardiol Rep 19(11):111. https://doi.org/10.1007/s11886-017-0919-x
Almeida SO, Budoff M (2019) Effect of statins on atherosclerotic plaque. Trends Cardiovasc Med 29(8):451–455. https://doi.org/10.1016/j.tcm.2019.01.001
Saiyitijiang A, Aizezi M, Zhao Y, Gao Y (2022) Efficacy and safety of new oral anticoagulants combined with antiplatelet drugs in the treatment of coronary heart disease: Systematic evaluation and meta-analysis. Ann Noninvasive Electrocardiol 27(5):e12977. https://doi.org/10.1111/anec.12977
MacCarthy EP, Bloomfield SS (1983) Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. Pharmacotherapy 3(4):193–219. https://doi.org/10.1002/j.1875-9114.1983.tb03252.x
McKenney JM (1988) Lovastatin: a new cholesterol-lowering agent. Clin Pharm 7(1):21–36
Samarraie Al, Pichette AM, Rousseau G (2023) Role of the gut microbiome in the development of atherosclerotic cardiovascular disease. Int J Mol Sci 24(6). https://doi.org/10.3390/ijms24065420
Jie Z, Xia H, Zhong SL, Feng Q, Li S, Liang S, Zhong H et al (2017) The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun 8(1):845. https://doi.org/10.1038/s41467-017-00900-1
Karlsson FH, Fak F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Backhed F, Nielsen J (2012) Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun 3:1245. https://doi.org/10.1038/ncomms2266
Jin L, Shi X, Yang J, Zhao Y, Xue L, Xu L, Cai J (2021) Gut microbes in cardiovascular diseases and their potential therapeutic applications. Protein Cell 12(5):346–359. https://doi.org/10.1007/s13238-020-00785-9
Hao H, Li Z, Qiao SY, Qi Y, Xu XY, Si JY, Liu YH et al (2023) Empagliflozin ameliorates atherosclerosis via regulating the intestinal flora. Atherosclerosis 371:32–40. https://doi.org/10.1016/j.atherosclerosis.2023.03.011
Abdi M, Esmaeili Gouvarchin Ghaleh H, Ranjbar R (2022) Lactobacilli and Bifidobacterium as anti-atherosclerotic agents. Iran J Basic Med Sci 25(8):934–946. https://doi.org/10.22038/IJBMS.2022.63860.14073
Cheng R, Zhang Y, Yang Y, Ren L, Li J, Wang Y, Shen X, He F (2022) Maternal gestational Bifidobacterium bifidum TMC3115 treatment shapes construction of offspring gut microbiota and development of immune system and induces immune tolerance to food allergen. Front Cell Infect Microbiol 12:1045109. https://doi.org/10.3389/fcimb.2022.1045109
Luo J, Li Y, Xie J, Gao L, Liu L, Ou S, Chen L, Peng X (2018) The primary biological network of Bifidobacterium in the gut. FEMS Microbiol Lett 365(8). https://doi.org/10.1093/femsle/fny057.
Al-Sheraji SH, Amin I, Azlan A, Manap MY, Hassan FA (2015) Effects of Bifidobacterium longum BB536 on lipid profile and histopathological changes in hypercholesterolaemic rats. Benef Microbes 6(5):661–668. https://doi.org/10.3920/BM2014.0032
Ma L, Zheng A, Ni L, Wu L, Hu L, Zhao Y, Fu Z, Ni Y (2022) Bifidobacterium animalis subsp. lactis lkm512 attenuates obesity-associated inflammation and insulin resistance through the modification of gut microbiota in high-fat diet-induced obese mice. Mol Nutr Food Res 66(3):e2100639. https://doi.org/10.1002/mnfr.202100639
Lau AS, Yanagisawa N, Hor YY, Lew LC, Ong JS, Chuah LO, Lee YY et al (2018) Bifidobacterium longum BB536 alleviated upper respiratory illnesses and modulated gut microbiota profiles in Malaysian pre-school children. Benef Microbes 9(1):61–70. https://doi.org/10.3920/BM2017.0063
Chen G, Wang M, Zeng Z, Xie M, Xu W, Peng Y, Zhou W, Sun Y, Zeng X, Liu Z (2022) Fuzhuan brick tea polysaccharides serve as a promising candidate for remodeling the gut microbiota from colitis subjects in vitro: Fermentation characteristic and anti-inflammatory activity. Food Chem 391:133203. https://doi.org/10.1016/j.foodchem.2022.133203
Yang L, Xie X, Li Y, Wu L, Fan C, Liang T, Xi Y et al (2021) Evaluation of the cholesterol-lowering mechanism of Enterococcus faecium strain 132 and Lactobacillus paracasei strain 201 in hypercholesterolemia rats.Nutrients 13(6). https://doi.org/10.3390/nu13061982
Li J, Cao Y, Lu R, Li H, Pang Y, Fu H, Fang G et al (2020) Integrated fecal microbiome and serum metabolomics analysis reveals abnormal changes in rats with immunoglobulin a nephropathy and the intervention effect of Zhen Wu Tang. Front Pharmacol 11:606689. https://doi.org/10.3389/fphar.2020.606689
Blaak EE, Canfora EE, Theis S, Frost G, Groen AK, Mithieux G, Nauta A et al (2020) Short chain fatty acids in human gut and metabolic health. Benef Microbes 11(5):411–455. https://doi.org/10.3920/BM2020.0057
Correa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MA (2016) Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunology 5(4):e73. https://doi.org/10.1038/cti.2016.17
Vinolo MA, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R (2011) Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem 22(9):849–855. https://doi.org/10.1016/j.jnutbio.2010.07.009
Brown JM, Hazen SL (2015) The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med 66:343–359. https://doi.org/10.1146/annurev-med-060513-093205
Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA (2019) Author Correction: Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol 16(10):642. https://doi.org/10.1038/s41575-019-0199-6
Emoto T, Yamashita T, Sasaki N, Hirota Y, Hayashi T, So A, Kasahara K et al (2016) Analysis of gut microbiota in coronary artery disease patients: a possible link between gut microbiota and coronary artery disease. J Atheroscler Thromb 23(8):908–921. https://doi.org/10.5551/jat.32672
Liu S, Zhao W, Liu X, Cheng L (2020) Metagenomic analysis of the gut microbiome in atherosclerosis patients identify cross-cohort microbial signatures and potential therapeutic target. Faseb J 34(11):14166–14181. https://doi.org/10.1096/fj.202000622R
Boo TW, Cryan B, O’Donnell A, Fahy G (2005) Prosthetic valve endocarditis caused by Veillonella parvula. J Infect 50(1):81–83. https://doi.org/10.1016/j.jinf.2003.11.008
Koren O, Spor A, Felin J, Fak F, Stombaugh J, Tremaroli V, Behre CJ et al (2011) Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A 108(Suppl 1):4592–4598. https://doi.org/10.1073/pnas.1011383107
El-Far M, Durand M, Turcotte I, Larouche-Anctil E, Sylla M, Zaidan S, Chartrand-Lefebvre C et al (2021) Upregulated IL-32 expression and reduced gut short chain fatty acid caproic acid in people living with HIV with subclinical atherosclerosis. Front Immunol 12:664371. https://doi.org/10.3389/fimmu.2021.664371
Alexander M, Ang QY, Nayak RR, Bustion AE, Sandy M, Zhang B, Upadhyay V, Pollard KS, Lynch SV, Turnbaugh PJ (2022) Human gut bacterial metabolism drives Th17 activation and colitis. Cell Host Microbe 30(1):17–30.e9. https://doi.org/10.1016/j.chom.2021.11.001
Eicher TP, Mohajeri MH (2022) Overlapping mechanisms of action of brain-active bacteria and bacterial metabolites in the pathogenesis of common brain diseases. Nutrients 14(13). https://doi.org/10.3390/nu14132661
Li J, Li Y, Ivey KL, Wang DD, Wilkinson JE, Franke A, Lee KH et al (2022) Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men. Gut 71(4):724–733. https://doi.org/10.1136/gutjnl-2020-322473
Ponziani FR, Nesci A, Caputo C, Salvatore L, Picca A, Del Chierico F, Paroni Sterbini F et al (2023) High prevalence of lower limb atherosclerosis is linked with the gut-liver axis in patients with primary biliary cholangitis. Liver Int 43(2):370–380. https://doi.org/10.1111/liv.15463
Wu F, Yang L, Islam MT, Jasmine F, Kibriya MG, Nahar J, Barmon B et al (2019) The role of gut microbiome and its interaction with arsenic exposure in carotid intima-media thickness in a Bangladesh population. Environ Int 123:104–113. https://doi.org/10.1016/j.envint.2018.11.049
Zhang L, Shi M, Ji J, Hu X, Chen F (2019) Gut microbiota determines the prevention effects of Luffa cylindrica (L.) Roem supplementation against obesity and associated metabolic disorders induced by high-fat diet. Faseb J 33(9):10339–10352. https://doi.org/10.1096/fj.201900488R
Romano KA, Vivas EI, Amador-Noguez D, Rey FE (2015) Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. mBio 6(2):e02481. https://doi.org/10.1128/mBio.02481-14
Aguilar EC, dos Santos LC, Leonel AJ, de Oliveira JS, Santos EA, Navia-Pelaez JM, da Silva JF et al (2016) Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells. J Nutr Biochem 34:99–105. https://doi.org/10.1016/j.jnutbio.2016.05.002
Li J, Liang J, Zeng M, Sun K, Luo Y, Zheng H, Li F et al (2022) Oxymatrine ameliorates white matter injury by modulating gut microbiota after intracerebral hemorrhage in mice. CNS Neurosci Ther. https://doi.org/10.1111/cns.14066
Li X, Wang C, Zhu J, Lin Q, Yu M, Wen J, Feng J, Hu C (2022) Sodium butyrate ameliorates oxidative stress-induced intestinal epithelium barrier injury and mitochondrial damage through AMPK-mitophagy pathway. Oxid Med Cell Longev 2022:3745135. https://doi.org/10.1155/2022/3745135
Liu S, Wu J, Wu Z, Alugongo GM, Zahoor Khan M, Li J, Xiao J et al (2022) Tributyrin administration improves intestinal development and health in pre-weaned dairy calves fed milk replacer. Anim Nutr 10:399–411. https://doi.org/10.1016/j.aninu.2022.06.004
Ohira H, Tsutsui W, Fujioka Y (2017) Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis? J Atheroscler Thromb 24(7):660–672. https://doi.org/10.5551/jat.RV17006
van den Munckhof ICL, Kurilshikov A, Ter Horst R, Riksen NP, Joosten LAB, Zhernakova A, Fu J et al (2018) Role of gut microbiota in chronic low-grade inflammation as potential driver for atherosclerotic cardiovascular disease: a systematic review of human studies. Obes Rev 19(12):1719–1734. https://doi.org/10.1111/obr.12750
Devaraj S, Yun JM, Duncan-Staley C, Jialal I (2009) C-reactive protein induces M-CSF release and macrophage proliferation. J Leukoc Biol 85(2):262–267. https://doi.org/10.1189/jlb.0808458
DeGruttola AK, Low D, Mizoguchi A, Mizoguchi E (2016) Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis 22(5):1137–1150. https://doi.org/10.1097/MIB.0000000000000750
Shi H, Li Y, Dong C, Si G, Xu Y, Peng M, Li Y (2022) Helicobacter pylori infection and the progression of atherosclerosis: A systematic review and meta-analysis. Helicobacter 27(1):e12865. https://doi.org/10.1111/hel.12865
Kim J, Jo Y, Cho D, Ryu D (2022) L-threonine promotes healthspan by expediting ferritin-dependent ferroptosis inhibition in C. elegans. Nat Commun 13(1):6554. https://doi.org/10.1038/s41467-022-34265-x
Mutanen A, Nissinen MJ, Lohi J, Heikkila P, Gylling H, Pakarinen MP (2014) Serum plant sterols, cholestanol, and cholesterol precursors associate with histological liver injury in pediatric onset intestinal failure. Am J Clin Nutr 100(4):1085–1094. https://doi.org/10.3945/ajcn.114.088781
Winkelman JW, Collins GH (1987) Neurotoxicity of tetraphenylporphinesulfonate TPPS4 and its relation to photodynamic therapy. Photochem Photobiol 46(5):801–807. https://doi.org/10.1111/j.1751-1097.1987.tb04851.x
Cao F, Jin L, Gao Y, Ding Y, Wen H, Qian Z, Zhang C et al (2023) Artificial-enzymes-armed Bifidobacterium longum probiotics for alleviating intestinal inflammation and microbiota dysbiosis. Nat Nanotechnol 18(6):617–627. https://doi.org/10.1038/s41565-023-01346-x
Fang Z, Pan T, Li L, Wang H, Zhu J, Zhang H, Zhao J, Chen W, Lu W (2022) Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis. Gut Microbes 14(1):2044723. https://doi.org/10.1080/19490976.2022.2044723
Vitellio P, Celano G, Bonfrate L, Gobbetti M, Portincasa M, De Angelis M (2019) Effects of Bifidobacterium longum and Lactobacillus rhamnosus on gut microbiota in patients with lactose intolerance and persisting functional gastrointestinal symptoms: a randomised, double-blind, cross-over study. Nutrients 11(4). https://doi.org/10.3390/nu11040886
Funding
This study was supported by the Project of National Key Research and Development (2021YFA0910200), Key Laboratory of Guangdong Province (2020B121201009), the GDAS Special Project of Capacity Building for Innovation-driven Development (2020GDASYL-20200103026) and Project by the Department of Science and Technology of Guangdong Province (2019QN01N107).
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YL, WQ and XX participated in the design of this study. YL, WJ, XX and LY contributed to this work and performed statistical analyses. WY, ZX, ZH and ZJ gathered important background information. YL drafted the manuscript. All authors read and approve the final manuscript.
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Yang, L., Wu, Y., Zhao, X. et al. An In Vitro Evaluation of the Effect of Bifidobacterium longum L556 on Microbiota Composition and Metabolic Properties in Patients with Coronary Heart Disease (CHD). Probiotics & Antimicro. Prot. (2024). https://doi.org/10.1007/s12602-024-10267-7
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DOI: https://doi.org/10.1007/s12602-024-10267-7