2021, Volume 7, Issue 12
Engineering >> 2021, Volume 7, Issue 12 doi: 10.1016/j.eng.2020.05.025
Gut Microbiota Community Shift with Severity of Coronary Artery Disease
a Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
b Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
c Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
d Department of Cardiology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China
e Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
# These authors contributed equally to this study.
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Abstract
Gut microbiota community shift with coronary artery disease (CAD) has been reported in several limited cohorts during the past several years. However, whether the enriched or decreased microbiota taxa with CAD can be reproducible deserves further investigation and validation. In this study, 78 human subjects were recruited. Of these, 19 were diagnosed without stenosis in coronary artery (control group, referred to herein as Ctrl), 14 with stenosis less than 50% (LT50), and 45 with stenosis greater than 50% (GT50). Fecal samples were collected and DNA was extracted to perform 16S rRNA gene sequencing. The operational taxonomic units (OTUs) were analyzed to identify taxa specific to different groups; next, multivariate logistic regression was employed to test whether the defined taxa could independently predict CAD risk. We found that Deltaproteobacteria, Fusobacterium, Bilophila, Actinomyces, and Clostridium XIX were enriched in Ctrl; Prevotellaceae, Parabacteriodes, and Butyricicoccus were enriched in LT50; and Roseburia and Butyricimonas were enriched in GT50. Further analysis revealed that increased populations of Deltaproteobacteria, Fusobacterium, Bilophila, and Desulfovibrionaceae were associated with a 0.26-fold, 0.21-fold, 0.18-fold, and 0.26-fold decreased risk of CAD, respectively (p < 0.05), and an increased Prevotellaceae population was associated with a 5.63-fold increased risk of CAD (p < 0.01). A combination of the 20 microbial taxa achieved an area under the receiver operating characteristic (ROC) curve of higher than 0.88 for all discriminations between LT50 vs Ctrl, GT50 vs Ctrl, LT50 + GT50 vs Ctrl, and GT50 vs Ctrl + LT50. However, the microbial taxa previously reported as enriched in CAD patients or healthy controls could not be observed in our cohort except for Bacteroides. In conclusion, CAD patients showed a different microbial taxa signature than the healthy controls. However, the non-reproducibility of the microbiota taxa enriched in CAD across different cohorts limits the use of this signature in early diagnosis and prevention. Only decreased Bacteroides abundance was found to be a reliable marker to indicate CAD progression.
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References
[ 1 ] Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients 2014;7(1):17–44. link1
[ 2 ] Nagao-Kitamoto H, Kitamoto S, Kuffa P, Kamada N. Pathogenic role of the gut microbiota in gastrointestinal diseases. Intest Res 2016;14(2):127–38. link1
[ 3 ] Donaldson DS, Mabbott NA. The influence of the commensal and pathogenic gut microbiota on prion disease pathogenesis. J Gen Virol 2016;97(8):1725–38. link1
[ 4 ] Budden KF, Gellatly SL, Wood DLA, Cooper MA, Morrison M, Hugenholtz P, et al. Emerging pathogenic links between microbiota and the gut–lung axis. Nat Rev Microbiol 2017;15(1):55–63. link1
[ 5 ] Brown JM, Hazen SL. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med 2015;66(1):343–59. link1
[ 6 ] Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: gut microbiota: the neglected endocrine organ. Mol Endocrinol 2014;28 (8):1221–38. link1
[ 7 ] Geurts L, Neyrinck AM, Delzenne NM, Knauf C, Cani PD. Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics. Beneficial Microbes 2014;5(1):3–17. link1
[ 8 ] Sun J, Chang EB. Exploring gut microbes in human health and disease: pushing the envelope. Genes Dis 2014;1(2):132–9. link1
[ 9 ] Emoto T, Yamashita T, Kobayashi T, Sasaki N, Hirota Y, Hayashi T, et al. Characterization of gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction fragment length polymorphism: gut microbiota could be a diagnostic marker of coronary artery disease. Heart Vessels 2017;32(1):39–46. link1
[10] Emoto T, Yamashita T, Sasaki N, Hirota Y, Hayashi T, So A, et al. Analysis of gut microbiota in coronary artery disease patients: a possible link between gut microbiota and coronary artery disease. J Atheroscler Thromb 2016;23 (8):908–21. link1
[11] Liu H, Chen X, Hu X, Niu H, Tian R, Wang H, et al. Alterations in the gut microbiome and metabolism with coronary artery disease severity. Microbiome 2019;7(1):68. link1
[12] Zhu Q, Gao R, Zhang Y, Pan D, Zhu Y, Zhang X, et al. Dysbiosis signatures of gut microbiota in coronary artery disease. Physiol Genomics 2018;50(10):893–903. link1
[13] Yoshida N, Sasaki K, Sasaki D, Yamashita T, Fukuda H, Hayashi T, et al. Effect of resistant starch on the gut microbiota and its metabolites in patients with coronary artery disease. J Arterioscler Thromb 2019;26(8):705–19. link1
[14] Wang F, Yu T, Huang G, Cai D, Liang X, Su H, et al. Gut microbiota community and its assembly associated with age and diet in Chinese centenarians. Microb Biotechnol 2015;25(8):1195–204. link1
[15] Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018;359 (6380):1151–6. link1
[16] Wang Z, Zhao Y. Gut microbiota derived metabolites in cardiovascular health and disease. Protein Cell 2018;9(5):416–31. link1
[17] Seldin MM, Meng Y, Qi H, Zhu WF, Wang Z, Hazen SL, et al. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogenactivated protein kinase and nuclear factor-jB. J Am Heart Assoc 2016;5(2): e002767. link1
[18] Barisione C, Ghigliotti G, Canepa M, Balbi M, Brunelli C, Ameri P. Indoxyl sulfate: a candidate target for the prevention and treatment of cardiovascular disease in chronic kidney disease. Curr Drug Targets 2015;16(4):366–72. link1
[19] Bogiatzi C, Gloor G, Allen-Vercoe E, Reid G, Wong RG, Urquhart BL, et al. Metabolic products of the intestinal microbiome and extremes of atherosclerosis. Atherosclerosis 2018;273:91–7. link1
[20] Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Lozupone CA, Turnbaugh PJ, et al. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proc Natl Acad Sci USA 2011;108(Suppl 1):4516–22. link1
[21] Li W, Godzik A. CD-HIT: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006;22(13):1658–9. link1
[22] Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol 2007;73(16):5261–7. link1
[23] Morris EK, Caruso T, Buscot F, Fischer M, Hancock C, Maier TS, et al. Choosing and using diversity indices: insights for ecological applications from the German Biodiversity Exploratories. Ecol Evol 2014;4(18):3514–24. link1
[24] Goecks J, Nekrutenko A. Taylor J; The Galaxy Team. Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. Genome Biol 2010;11(8):R86. link1
[25] Blankenberg D, Von Kuster G, Coraor N, Ananda G, Lazarus R, Mangan M, et al. Galaxy: a web-based genome analysis tool for experimentalists. Curr Protoc Mol Biol 2010;89(1):19.10.1–21.
[26] Xia J, Wishart DS. Using MetaboAnalyst 3.0 for comprehensive metabolomics data analysis. Curr Protoc Bioinformatics 2016;55:14.10.1–91.
[27] Chong J, Liu P, Zhou G, Xia J. Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data. Nat Protoc 2020;15(3):799–821. link1
[28] Dhariwal A, Chong J, Habib S, King IL, Agellon LB, Xia J. MicrobiomeAnalyst—a web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data. Nucleic Acids Res 2017;45(W1):W180–8. link1
[29] Talayero BG, Sacks FM. The role of triglycerides in atherosclerosis. Curr Cardiol Rep 2011;13(6):544–52. link1
[30] Norhammar A, Malmberg K, Diderholm E, Lagerqvist B, Lindahl B, Rydén L, et al. Diabetes mellitus: the major risk factor in unstable coronary artery disease even after consideration of the extent of coronary artery disease and benefits of revascularization. J Am Coll Cardiol 2004;43(4):585–91. link1
[31] Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature 2011;473(7346): 174–80. link1
[32] Wu GD, Chen J, Hoffmann C, Bittinger K, Chen Y, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011;334 (6052):105–8. link1
[33] Koliada A, Syzenko G, Moseiko V, Budovska L, Puchkov K, Perederiy V, et al. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol 2017;17:120. link1
[34] Wilson PW, Castelli WP, Kannel WB. Coronary risk prediction in adults (The Framingham Heart Study). Am J Cardiol 1987;59(14). G91–4. link1
[35] Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;108(17):2154–69. link1
[36] Jie Z, Xia H, Zhong SL, Feng Q, Li S, Liang S, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun 2017;8(1):845. link1
[37] Yin J, Liao SX, He Y, Wang S, Xia GH, Liu FT, et al. Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack. J Am Heart Assoc 2015;4 (11):e002699. link1
[38] Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun 2012;3:1245. link1
[39] Kasahara K, Krautkramer KA, Org E, Romano KA, Kerby RL, Vivas EI, et al. Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model. Nat Microbiol 2018;3(12):1461–71. link1
[40] de Moraes AC, Fernandes GR, da Silva IT, Almeida-Pititto B, Gomes EP, Pereira AD, et al. Enterotype may drive the dietary-associated cardiometabolic risk factors. Front Cell Infect Microbiol 2017;7:47. link1
[41] Glick-Bauer M, Yeh MC. The health advantage of a vegan diet: exploring the gut microbiota connection. Nutrients 2014;6(11):4822–38. link1
[42] De Filippis F, Pellegrini N, Laghi L, Gobbetti M, Ercolini D. Unusual sub-genus associations of faecal Prevotella and Bacteroides with specific dietary patterns. Microbiome 2016;4(1):57. link1
[43] Stock J. Gut microbiota: an environmental risk factor for cardiovascular disease. Atherosclerosis 2013;229(2):440–2. link1
[44] Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013;368(17):1575–84. link1
[45] Wang Z, Roberts AB, Buffa JA, Levison BS, Zhu W, Org E, et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 2015;163(7):1585–95. link1
[46] Yamashita T. Intestinal immunity and gut microbiota in atherogenesis. J Atheroscler Thromb 2017;24(2):110–9. link1
[47] Makarova K, Slesarev A, Wolf Y, Sorokin A, Mirkin B, Koonin E, et al. Comparative genomics of the lactic acid bacteria. Proc Natl Acad Sci USA 2006;103(42):15611–6. link1
[48] Giuliano C, Khan AW. Conversion of cellulose to sugars by resting cells of a mesophilic anaerobe Bacteriodes cellulosolvens. Biotechnol Bioeng 1985;27 (7):980–3. link1
[49] Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients 2015;7(4):2839–49. link1
[50] Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci USA 2013;110 (11):4410–5. link1
[51] Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes 2014;5(2):202–7. link1
[52] Allen-Vercoe E, Strauss J, Chadee K. Fusobacterium nucleatum: an emerging gut pathogen? Gut Microbes 2011;2(5):294–8. link1
[53] Han YW, Ikegami A, Rajanna C, Kawsar HI, Zhou Y, Li M, et al. Identification and characterization of a novel adhesin unique to oral Fusobacteria. J Bacteriol 2005;187(15):5330–40. link1
[54] Velsko IM, Chukkapalli SS, Rivera-Kweh MF, Chen H, Zheng D, Bhattacharyya I, et al. Fusobacterium nucleatum alters atherosclerosis risk factors and enhances inflammatory markers with an atheroprotective immune response in ApoE (null) mice. PLoS ONE 2015;10(6):e0129795. link1
[55] David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505(7484):559–63. link1
[56] Miller TW, Wang EA, Gould S, Stein EV, Kaur S, Lim L, et al. Hydrogen sulfide is an endogenous potentiator of T cell activation. J Biol Chem 2012;287 (6):4211–21. link1
[57] Pitcher MC, Cummings JH. Hydrogen sulphide: a bacterial toxin in ulcerative colitis? Gut 1996;39(1):1–4. link1
[58] Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun 2015;48:186–94. link1
[59] Nakayama J, Yamamoto A, Palermo-Conde LA, Higashi K, Sonomoto K, Tan J, et al. Impact of westernized diet on gut microbiota in children on Leyte Island. Front Microbiol 2017;8:197. link1
[60] Heinritz SN, Weiss E, Eklund M, Aumiller T, Louis S, Rings A, et al. Intestinal microbiota and microbial metabolites are changed in a pig model fed a highfat/low-fiber or a low-fat/high-fiber diet. PLoS ONE 2016;11(4):e0154329. link1
[61] Serena C, Ceperuelo-Mallafre V, Keiran N, Queipo-Ortuño MI, Bernal R, GomezHuelgas R, et al. Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota. ISME J 2018;12(7):1642–57. link1
[62] Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 2015;30(3):350–8. link1
[63] London LE, Kumar AH, Wall R, Casey PG, O’Sullivan O, Shanahan F, et al. Exopolysaccharide-producing probiotic Lactobacilli reduce serum cholesterol and modify enteric microbiota in ApoE-deficient mice. J Nutr 2014;144 (12):1956–62. link1
[64] Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int 2013;83(2):308–15. link1
[65] Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord 2016;32:66–72. link1
[66] Jeffery ND, Barker AK, Alcott CJ, Levine JM, Meren I, Wengert J, et al. The association of specific constituents of the fecal microbiota with immunemediated brain disease in dogs. PLoS ONE 2017;12(1):e0170589. link1
[67] Zhang X, Wang H, Yin P, Fan H, Sun L, Liu Y. Flaxseed oil ameliorates alcoholic liver disease via anti-inflammation and modulating gut microbiota in mice. Lipids Health Dis 2017;16:44. link1
[68] Ishioka M, Miura K, Minami S, Shimura Y, Ohnishi H. Altered gut microbiota composition and immune response in experimental steatohepatitis mouse models. Dig Dis Sci 2017;62(2):396–406. link1
[69] Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Paz Soldan MM, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep 2016;6:28484. link1
[70] Matziouridou C, Marungruang N, Nguyen TD, Nyman M, Fak F. Lingonberries reduce atherosclerosis in Apoe(–/–) mice in association with altered gut microbiota composition and improved lipid profile. Mol Nutr Food Res 2016;60(5):1150–60. link1
[71] Li W, Zhang K, Yang H. Pectin alleviates high fat (lard) diet-induced nonalcoholic fatty liver disease in mice: possible role of short-chain fatty acids and gut microbiota regulated by pectin. J Agric Food Chem 2018;66(30):8015–25. link1
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