CoChat
Sign Up
Cited by 1,670Gut microbiota and healthOral microbiology and periodontitis researchNutritional Studies and Diet

Gut microbiota in cardiovascular health and disease

Open access
Tang, W.H. Wilson, Kitai, Takeshi, Hazen, Stanley L.·2017·Circulation Research
DOI 10.1161/circresaha.117.309715PMC PMC5390330
Open this paper in CoChat — free accountOpen PDF

Abstract

Significant interest in recent years has focused on gut microbiota–host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine N -oxide pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these metabolism-dependent pathways, metabolism-independent processes are suggested to also potentially contribute to cardiovascular disease pathogenesis. For example, heart failure–associated splanchnic circulation congestion, bowel wall edema, and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are thought to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/circresaha.117.309715

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Changes in the intestinal microbiota can lead to the production of compounds such as trimethylamine N-oxide (TMAO), which increase the risk of developing cardiovascular diseases.

    “In addition, changes in the intestinal microbiota can lead to the production of compounds such as trimethylamine N-oxide (TMAO), which increase the risk of developing cardiovascular diseases (79, 80).”

    From Kefir and Intestinal Microbiota Modulation: Implications in Human Health (2021) · cites this paper as [79]

    The Atherosclerosis, Coronary Artery Disease and Myocardial Infarction section explains that gut microbes generate TMA, which the liver converts to TMAO, and reports associations between TMAO levels and cardiovascular risk. It also says that TMAO’s causative effects remain uncertain and that whether targeting the pathway reduces cardiovascular risk in humans is unknown. Thus, the claim’s unqualified statement that TMAO increases risk overstates the source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 150

  1. [1]Mozaffarian D Benjamin EJ Go AS Arnett DK Blaha MJ Cushman M Das SR de Ferranti S Despres JP Fullerton HJ Howard VJ Huffman MD Isasi CR Jimenez MC Judd SE Kissela BM Lichtman JH Lisabeth LD Liu S Mackey RH Magid DJ McGuire DK Mohler ER 3rd Moy CS Muntner P Mussolino ME Nasir K Neumar RW Nichol G Palaniappan L Pandey DK Reeves MJ Rodriguez CJ Rosamond W Sorlie PD Stein J Towfighi A Turan TN Virani SS Woo D Yeh RW Turner MB Heart disease and stroke statistics-2016 update: A report from the american heart association Circulation 2016 133 e38 360 26673558
  2. [2]Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: A systematic analysis for the global burden of disease study 2013 Lancet 2015 385 117 171 25530442 PMC4340604
  3. [3]Koren O Spor A Felin J Fak F Stombaugh J Tremaroli V Behre CJ Knight R Fagerberg B Ley RE Backhed F Human oral, gut, and plaque microbiota in patients with atherosclerosis Proc Natl Acad Sci U S A 2011 108 Suppl 1 4592 4598 20937873 PMC3063583
  4. [5]Yamashiro K Tanaka R Urabe T Ueno Y Yamashiro Y Nomoto K Takahashi T Tsuji H Asahara T Hattori N Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke PLoS One 2017 12 e0171521 28166278 PMC5293236
  5. [6]Turnbaugh PJ Ley RE Mahowald MA Magrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased capacity for energy harvest Nature 2006 444 1027 1031 17183312
  6. [7]Fak F Backhed F Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in apoe−/− mice PLoS One 2012 7 e46837 23056479 PMC3467285
  7. [8]Wang Z Klipfell E Bennett BJ Koeth R Levison BS Dugar B Feldstein AE Britt EB Fu X Chung YM Wu Y Schauer P Smith JD Allayee H Tang WH DiDonato JA Lusis AJ Hazen SL Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease Nature 2011 472 57 63 21475195 PMC3086762
  8. [9]Koeth RA Wang Z Levison BS Buffa JA Org E Sheehy BT Britt EB Fu X Wu Y Li L Smith JD DiDonato JA Chen J Li H Wu GD Lewis JD Warrier M Brown JM Krauss RM Tang WH Bushman FD Lusis AJ Hazen SL Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis Nat Med 2013 19 576 585 23563705 PMC3650111
  9. [10]Zhu W Gregory JC Org E Buffa JA Gupta N Wang Z Li L Fu X Wu Y Mehrabian M Sartor RB McIntyre TM Silverstein RL Tang WH DiDonato JA Brown JM Lusis AJ Hazen SL Gut microbial metabolite tmao enhances platelet hyperreactivity and thrombosis risk Cell 2016 165 111 124 26972052 PMC4862743
  10. [11]Pluznick JL Protzko RJ Gevorgyan H Peterlin Z Sipos A Han J Brunet I Wan LX Rey F Wang T Firestein SJ Yanagisawa M Gordon JI Eichmann A Peti-Peterdi J Caplan MJ Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation Proc Natl Acad Sci U S A 2013 110 4410 4415 23401498 PMC3600440
  11. [14]Kimura I Ozawa K Inoue D Imamura T Kimura K Maeda T Terasawa K Kashihara D Hirano K Tani T Takahashi T Miyauchi S Shioi G Inoue H Tsujimoto G The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor gpr43 Nat Commun 2013 4 1829 23652017 PMC3674247
  12. [15]De Vadder F Kovatcheva-Datchary P Goncalves D Vinera J Zitoun C Duchampt A Backhed F Mithieux G Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits Cell 2014 156 84 96 24412651
  13. [17]Watanabe M Houten SM Mataki C Christoffolete MA Kim BW Sato H Messaddeq N Harney JW Ezaki O Kodama T Schoonjans K Bianco AC Auwerx J Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation Nature 2006 439 484 489 16400329
  14. [19]Pols TW Nomura M Harach T Lo Sasso G Oosterveer MH Thomas C Rizzo G Gioiello A Adorini L Pellicciari R Auwerx J Schoonjans K Tgr5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading Cell Metab 2011 14 747 757 22152303 PMC3627293
  15. [20]Ma K Saha PK Chan L Moore DD Farnesoid x receptor is essential for normal glucose homeostasis J Clin Invest 2006 116 1102 1109 16557297 PMC1409738
  16. [21]Downes M Verdecia MA Roecker AJ Hughes R Hogenesch JB Kast-Woelbern HR Bowman ME Ferrer JL Anisfeld AM Edwards PA Rosenfeld JM Alvarez JG Noel JP Nicolaou KC Evans RM A chemical, genetic, and structural analysis of the nuclear bile acid receptor fxr Mol Cell 2003 11 1079 1092 12718892 PMC6179153
  17. [23]Neish AS Microbes in gastrointestinal health and disease Gastroenterology 2009 136 65 80 19026645 PMC2892787
  18. [24]Sekirov I Russell SL Antunes LC Finlay BB Gut microbiota in health and disease Physiol Rev 2010 90 859 904 20664075
  19. [25]Nallu A Sharma S Ramezani A Muralidharan J Raj D Gut microbiome in chronic kidney disease: Challenges and opportunities Transl Res 2017 179 24 37 27187743 PMC5086447
  20. [27]Savage DC Associations of indigenous microorganisms with gastrointestinal mucosal epithelia Am J Clin Nutr 1970 23 1495 1501 5475367
  21. [28]Backhed F Ding H Wang T Hooper LV Koh GY Nagy A Semenkovich CF Gordon JI The gut microbiota as an environmental factor that regulates fat storage Proc Natl Acad Sci U S A 2004 101 15718 15723 15505215 PMC524219
  22. [29]Mazmanian SK Liu CH Tzianabos AO Kasper DL An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system Cell 2005 122 107 118 16009137
  23. [30]Li M Wang B Zhang M Rantalainen M Wang S Zhou H Zhang Y Shen J Pang X Wei H Chen Y Lu H Zuo J Su M Qiu Y Jia W Xiao C Smith LM Yang S Holmes E Tang H Zhao G Nicholson JK Li L Zhao L Symbiotic gut microbes modulate human metabolic phenotypes Proc Natl Acad Sci U S A 2008 105 2117 2122 18252821 PMC2538887
  24. [31]Rakoff-Nahoum S Paglino J Eslami-Varzaneh F Edberg S Medzhitov R Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis Cell 2004 118 229 241 15260992
  25. [33]Tamburini S Shen N Wu HC Clemente JC The microbiome in early life: Implications for health outcomes Nat Med 2016 22 713 722 27387886
  26. [34]Carmody RN Gerber GK Luevano JM Jr Gatti DM Somes L Svenson KL Turnbaugh PJ Diet dominates host genotype in shaping the murine gut microbiota Cell Host Microbe 2015 17 72 84 25532804 PMC4297240
  27. [35]Tremaroli V Backhed F Functional interactions between the gut microbiota and host metabolism Nature 2012 489 242 249 22972297
  28. [38]Ott SJ El Mokhtari NE Musfeldt M Hellmig S Freitag S Rehman A Kuhbacher T Nikolaus S Namsolleck P Blaut M Hampe J Sahly H Reinecke A Haake N Gunther R Kruger D Lins M Herrmann G Folsch UR Simon R Schreiber S Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease Circulation 2006 113 929 937 16490835
  29. [39]Larsson E Tremaroli V Lee YS Koren O Nookaew I Fricker A Nielsen J Ley RE Backhed F Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through myd88 Gut 2012 61 1124 1131 22115825 PMC3388726
  30. [40]Brown JM Hazen SL The gut microbial endocrine organ: Bacterially derived signals driving cardiometabolic diseases Annu Rev Med 2015 66 343 359 25587655 PMC4456003
  31. [41]Cani PD Possemiers S Van de Wiele T Guiot Y Everard A Rottier O Geurts L Naslain D Neyrinck A Lambert DM Muccioli GG Delzenne NM Changes in gut microbiota control inflammation in obese mice through a mechanism involving glp-2-driven improvement of gut permeability Gut 2009 58 1091 1103 19240062 PMC2702831
  32. [42]Cani PD Amar J Iglesias MA Poggi M Knauf C Bastelica D Neyrinck AM Fava F Tuohy KM Chabo C Waget A Delmee E Cousin B Sulpice T Chamontin B Ferrieres J Tanti JF Gibson GR Casteilla L Delzenne NM Alessi MC Burcelin R Metabolic endotoxemia initiates obesity and insulin resistance Diabetes 2007 56 1761 1772 17456850
  33. [43]Medzhitov R Recognition of microorganisms and activation of the immune response Nature 2007 449 819 826 17943118
  34. [44]Ryan KK Tremaroli V Clemmensen C Kovatcheva-Datchary P Myronovych A Karns R Wilson-Perez HE Sandoval DA Kohli R Backhed F Seeley RJ Fxr is a molecular target for the effects of vertical sleeve gastrectomy Nature 2014 509 183 188 24670636 PMC4016120
  35. [46]Perry RJ Peng L Barry NA Cline GW Zhang D Cardone RL Petersen KF Kibbey RG Goodman AL Shulman GI Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome Nature 2016 534 213 217 27279214 PMC4922538
  36. [47]Mattila KJ Nieminen MS Valtonen VV Rasi VP Kesaniemi YA Syrjala SL Jungell PS Isoluoma M Hietaniemi K Jokinen MJ Association between dental health and acute myocardial infarction BMJ 1989 298 779 781 2496855 PMC1836063
  37. [48]Hyvarinen K Mantyla P Buhlin K Paju S Nieminen MS Sinisalo J Pussinen PJ A common periodontal pathogen has an adverse association with both acute and stable coronary artery disease Atherosclerosis 2012 223 478 484 22704805
  38. [49]Fak F Tremaroli V Bergstrom G Backhed F Oral microbiota in patients with atherosclerosis Atherosclerosis 2015 243 573 578 26536303
  39. [50]Serra e Silva Filho W Casarin RC Nicolela EL Jr Passos HM Sallum AW Goncalves RB Microbial diversity similarities in periodontal pockets and atheromatous plaques of cardiovascular disease patients PLoS One 2014 9 e109761 25329160 PMC4199612
  40. [51]Lam V Su J Koprowski S Hsu A Tweddell JS Rafiee P Gross GJ Salzman NH Baker JE Intestinal microbiota determine severity of myocardial infarction in rats FASEB J 2012 26 1727 1735 22247331 PMC3316900
  41. [52]Lam V Su J Hsu A Gross GJ Salzman NH Baker JE Intestinal microbial metabolites are linked to severity of myocardial infarction in rats PLoS One 2016 11 e0160840 27505423 PMC4978455
  42. [54]Tang WH Hazen SL The contributory role of gut microbiota in cardiovascular disease J Clin Invest 2014 124 4204 4211 25271725 PMC4215189
  43. [55]Koeth RA Levison BS Culley MK Buffa JA Wang Z Gregory JC Org E Wu Y Li L Smith JD Tang WH DiDonato JA Lusis AJ Hazen SL Gamma-butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of l-carnitine to tmao Cell Metab 2014 20 799 812 25440057 PMC4255476
  44. [56]Craciun S Balskus EP Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme Proc Natl Acad Sci U S A 2012 109 21307 21312 23151509 PMC3535645
  45. [57]Chen Y Patel NA Crombie A Scrivens JH Murrell JC Bacterial flavin-containing monooxygenase is trimethylamine monooxygenase Proc Natl Acad Sci U S A 2011 108 17791 17796 22006322 PMC3203794
  46. [60]Tang WH Wang Z Fan Y Levison B Hazen JE Donahue LM Wu Y Hazen SL Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-n-oxide in patients with heart failure: Refining the gut hypothesis J Am Coll Cardiol 2014 64 1908 1914 25444145 PMC4254529
  47. [61]Tang WH Wang Z Shrestha K Borowski AG Wu Y Troughton RW Klein AL Hazen SL Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure J Card Fail 2015 21 91 96 25459686 PMC4312712
  48. [62]Senthong V Wang Z Fan Y Wu Y Hazen SL Tang WH Trimethylamine n-oxide and mortality risk in patients with peripheral artery disease J Am Heart Assoc 2016 5 PMC5121520 27792653
  49. [63]Fu Q Zhao M Wang D Hu H Guo C Chen W Li Q Zheng L Chen B Coronary plaque characterization assessed by optical coherence tomography and plasma trimethylamine-n-oxide levels in patients with coronary artery disease Am J Cardiol 2016 118 1311 1315 27600460
  50. [64]Li XS Obeid S Klingenberg R Gencer B Mach F Raber L Windecker S Rodondi N Nanchen D Muller O Miranda MX Matter CM Wu Y Li L Wang Z Alamri HS Gogonea V Chung YM Tang WH Hazen SL Luscher TF Gut microbiota-dependent trimethylamine n-oxide in acute coronary syndromes: A prognostic marker for incident cardiovascular events beyond traditional risk factors Eur Heart J 2017 11 28077467 PMC5837488
  51. [65]Wang Z Roberts AB Buffa JA Levison BS Zhu W Org E Gu X Huang Y Zamanian-Daryoush M Culley MK DiDonato AJ Fu X Hazen JE Krajcik D DiDonato JA Lusis AJ Hazen SL Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis Cell 2015 163 1585 1595 26687352 PMC4871610
  52. [68]Mell B Jala VR Mathew AV Byun J Waghulde H Zhang Y Haribabu B Vijay-Kumar M Pennathur S Joe B Evidence for a link between gut microbiota and hypertension in the dahl rat Physiol Genomics 2015 47 187 197 25829393 PMC4451389
  53. [69]Qi Y Aranda JM Rodriguez V Raizada MK Pepine CJ Impact of antibiotics on arterial blood pressure in a patient with resistant hypertension - a case report Int J Cardiol 2015 201 157 158 26301638 PMC4711349
  54. [70]Adnan S Nelson JW Ajami NJ Venna VR Petrosino JF Bryan RM Jr Durgan DJ Alterations in the gut microbiota can elicit hypertension in rats Physiol Genomics 2017 49 96 104 28011881 PMC5336599
  55. [71]Karbach SH Schonfelder T Brandao I Wilms E Hormann N Jackel S Schuler R Finger S Knorr M Lagrange J Brandt M Waisman A Kossmann S Schafer K Munzel T Reinhardt C Wenzel P Gut microbiota promote angiotensin ii-induced arterial hypertension and vascular dysfunction J Am Heart Assoc 2016 5 PMC5079031 27577581
  56. [72]Gomez-Arango LF Barrett HL McIntyre HD Callaway LK Morrison M Dekker Nitert M Increased systolic and diastolic blood pressure is associated with altered gut microbiota composition and butyrate production in early pregnancy Hypertension 2016 68 974 981 27528065
  57. [73]Evans JM Morris LS Marchesi JR The gut microbiome: The role of a virtual organ in the endocrinology of the host J Endocrinol 2013 218 R37 47 23833275
  58. [74]Pluznick JL Renal and cardiovascular sensory receptors and blood pressure regulation Am J Physiol Renal Physiol 2013 305 F439 444 23761671 PMC3891255
  59. [75]Sharkey KA Savidge TC Role of enteric neurotransmission in host defense and protection of the gastrointestinal tract Auton Neurosci 2014 181 94 106 24412639 PMC3944077
  60. [76]Santisteban MM Qi Y Zubcevic J Kim S Yang T Shenoy V Cole-Jeffrey CT Lobaton GO Stewart DC Rubiano A Simmons CS Garcia-Pereira F Johnson RD Pepine CJ Raizada MK Hypertension-linked pathophysiological alterations in the gut Circ Res 2017 120 312 323 27799253 PMC5250568
  61. [77]Palsson J Ricksten SE Delle M Lundin S Changes in renal sympathetic nerve activity during experimental septic and endotoxin shock in conscious rats Circ Shock 1988 24 133 141 3286033
  62. [78]Straub RH Pongratz G Weidler C Linde HJ Kirschning CJ Gluck T Scholmerich J Falk W Ablation of the sympathetic nervous system decreases gram-negative and increases gram-positive bacterial dissemination: Key roles for tumor necrosis factor/phagocytes and interleukin-4/lymphocytes J Infect Dis 2005 192 560 572 16028124
  63. [80]Kawase M Hashimoto H Hosoda M Morita H Hosono A Effect of administration of fermented milk containing whey protein concentrate to rats and healthy men on serum lipids and blood pressure J Dairy Sci 2000 83 255 263 10714858
  64. [82]Gomez-Guzman M Toral M Romero M Jimenez R Galindo P Sanchez M Zarzuelo MJ Olivares M Galvez J Duarte J Antihypertensive effects of probiotics lactobacillus strains in spontaneously hypertensive rats Mol Nutr Food Res 2015 59 2326 2336 26255877
  65. [83]Khalesi S Sun J Buys N Jayasinghe R Effect of probiotics on blood pressure: A systematic review and meta-analysis of randomized, controlled trials Hypertension 2014 64 897 903 25047574
  66. [84]Sandek A Bauditz J Swidsinski A Buhner S Weber-Eibel J von Haehling S Schroedl W Karhausen T Doehner W Rauchhaus M Poole-Wilson P Volk HD Lochs H Anker SD Altered intestinal function in patients with chronic heart failure J Am Coll Cardiol 2007 50 1561 1569 17936155
  67. [85]Krack A Richartz BM Gastmann A Greim K Lotze U Anker SD Figulla HR Studies on intragastric pco2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure Eur J Heart Fail 2004 6 403 407 15182764
  68. [86]Niebauer J Volk HD Kemp M Dominguez M Schumann RR Rauchhaus M Poole-Wilson PA Coats AJ Anker SD Endotoxin and immune activation in chronic heart failure: A prospective cohort study Lancet 1999 353 1838 1842 10359409
  69. [87]Sandek A Swidsinski A Schroedl W Watson A Valentova M Herrmann R Scherbakov N Cramer L Rauchhaus M Grosse-Herrenthey A Krueger M von Haehling S Doehner W Anker SD Bauditz J Intestinal blood flow in patients with chronic heart failure: A link with bacterial growth, gastrointestinal symptoms, and cachexia J Am Coll Cardiol 2014 64 1092 1102 25212642
  70. [88]Pasini E Aquilani R Testa C Baiardi P Angioletti S Boschi F Verri M Dioguardi F Pathogenic gut flora in patients with chronic heart failure JACC Heart Fail 2016 4 220 227 26682791
  71. [89]Wang Z Tang WH Buffa JA Fu X Britt EB Koeth RA Levison BS Fan Y Wu Y Hazen SL Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-n-oxide Eur Heart J 2014 35 904 910 24497336 PMC3977137
  72. [91]Ley RE Backhed F Turnbaugh P Lozupone CA Knight RD Gordon JI Obesity alters gut microbial ecology Proc Natl Acad Sci U S A 2005 102 11070 11075 16033867 PMC1176910
  73. [92]Turnbaugh PJ Hamady M Yatsunenko T Cantarel BL Duncan A Ley RE Sogin ML Jones WJ Roe BA Affourtit JP Egholm M Henrissat B Heath AC Knight R Gordon JI A core gut microbiome in obese and lean twins Nature 2009 457 480 484 19043404 PMC2677729
  74. [94]Larsen N Vogensen FK van den Berg FW Nielsen DS Andreasen AS Pedersen BK Al-Soud WA Sorensen SJ Hansen LH Jakobsen M Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults PLoS One 2010 5 e9085 20140211 PMC2816710
  75. [96]Donohoe DR Wali A Brylawski BP Bultman SJ Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes PLoS One 2012 7 e46589 23029553 PMC3460890
  76. [97]Meyer TW Hostetter TH Uremic solutes from colon microbes Kidney Int 2012 81 949 954 22318422
  77. [99]Vrieze A Out C Fuentes S Jonker L Reuling I Kootte RS van Nood E Holleman F Knaapen M Romijn JA Soeters MR Blaak EE Dallinga-Thie GM Reijnders D Ackermans MT Serlie MJ Knop FK Holst JJ van der Ley C Kema IP Zoetendal EG de Vos WM Hoekstra JB Stroes ES Groen AK Nieuwdorp M Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity J Hepatol 2014 60 824 831 24316517
  78. [100]Sharma M Thandassery RB Bhargava N Double pylorus: An optical illusion or reality? Gastroenterology 2012 143 e7 8 22727855
  79. [101]Maslowski KM Vieira AT Ng A Kranich J Sierro F Yu D Schilter HC Rolph MS Mackay F Artis D Xavier RJ Teixeira MM Mackay CR Regulation of inflammatory responses by gut microbiota and chemoattractant receptor gpr43 Nature 2009 461 1282 1286 19865172 PMC3256734
  80. [103]Tolhurst G Heffron H Lam YS Parker HE Habib AM Diakogiannaki E Cameron J Grosse J Reimann F Gribble FM Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the g-protein-coupled receptor ffar2 Diabetes 2012 61 364 371 22190648 PMC3266401
  81. [104]Fava S Glucagon-like peptide 1 and the cardiovascular system Curr Diabetes Rev 2014 10 302 310 25360712
  82. [105]Chambers ES Viardot A Psichas A Morrison DJ Murphy KG Zac-Varghese SE MacDougall K Preston T Tedford C Finlayson GS Blundell JE Bell JD Thomas EL Mt-Isa S Ashby D Gibson GR Kolida S Dhillo WS Bloom SR Morley W Clegg S Frost G Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults Gut 2015 64 1744 1754 25500202 PMC4680171
  83. [107]Midtvedt T Microbial bile acid transformation Am J Clin Nutr 1974 27 1341 1347 4217103
  84. [108]Russell DW The enzymes, regulation, and genetics of bile acid synthesis Annu Rev Biochem 2003 72 137 174 12543708
  85. [111]Lefebvre P Cariou B Lien F Kuipers F Staels B Role of bile acids and bile acid receptors in metabolic regulation Physiol Rev 2009 89 147 191 19126757
  86. [112]Sayin SI Wahlstrom A Felin J Jantti S Marschall HU Bamberg K Angelin B Hyotylainen T Oresic M Backhed F Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring fxr antagonist Cell Metab 2013 17 225 235 23395169
  87. [113]Li F Jiang C Krausz KW Li Y Albert I Hao H Fabre KM Mitchell JB Patterson AD Gonzalez FJ Microbiome remodelling leads to inhibition of intestinal farnesoid x receptor signalling and decreased obesity Nat Commun 2013 4 2384 24064762 PMC6595219
  88. [114]Jiang C Xie C Li F Zhang L Nichols RG Krausz KW Cai J Qi Y Fang ZZ Takahashi S Tanaka N Desai D Amin SG Albert I Patterson AD Gonzalez FJ Intestinal farnesoid x receptor signaling promotes nonalcoholic fatty liver disease J Clin Invest 2015 125 386 402 25500885 PMC4382255
  89. [115]Islam KB Fukiya S Hagio M Fujii N Ishizuka S Ooka T Ogura Y Hayashi T Yokota A Bile acid is a host factor that regulates the composition of the cecal microbiota in rats Gastroenterology 2011 141 1773 1781 21839040
  90. [117]Ahmad NN Pfalzer A Kaplan LM Roux-en-y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity Int J Obes (Lond) 2013 37 1553 1559 23567924 PMC4157126
  91. [118]Kohli R Bradley D Setchell KD Eagon JC Abumrad N Klein S Weight loss induced by roux-en-y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids J Clin Endocrinol Metab 2013 98 E708 712 23457410 PMC3615197
  92. [120]Nakatani H Kasama K Oshiro T Watanabe M Hirose H Itoh H Serum bile acid along with plasma incretins and serum high-molecular weight adiponectin levels are increased after bariatric surgery Metabolism 2009 58 1400 1407 19570554
  93. [121]Pournaras DJ Glicksman C Vincent RP Kuganolipava S Alaghband-Zadeh J Mahon D Bekker JH Ghatei MA Bloom SR Walters JR Welbourn R le Roux CW The role of bile after roux-en-y gastric bypass in promoting weight loss and improving glycaemic control Endocrinology 2012 153 3613 3619 22673227 PMC3404349
  94. [123]le Roux CW Bloom SR Why do patients lose weight after roux-en-y gastric bypass? J Clin Endocrinol Metab 2005 90 591 592 15643022
  95. [124]Miras AD le Roux CW Mechanisms underlying weight loss after bariatric surgery Nat Rev Gastroenterol Hepatol 2013 10 575 584 23835488
  96. [127]Warrier M Shih DM Burrows AC Ferguson D Gromovsky AD Brown AL Marshall S McDaniel A Schugar RC Wang Z Sacks J Rong X Vallim TA Chou J Ivanova PT Myers DS Brown HA Lee RG Crooke RM Graham MJ Liu X Parini P Tontonoz P Lusis AJ Hazen SL Temel RE Brown JM The tmao-generating enzyme flavin monooxygenase 3 is a central regulator of cholesterol balance Cell Rep 2015 14 01065 01061 PMC4501903 25600868
  97. [128]Ronco C Haapio M House AA Anavekar N Bellomo R Cardiorenal syndrome J Am Coll Cardiol 2008 52 1527 1539 19007588
  98. [129]Gansevoort RT Correa-Rotter R Hemmelgarn BR Jafar TH Heerspink HJ Mann JF Matsushita K Wen CP Chronic kidney disease and cardiovascular risk: Epidemiology, mechanisms, and prevention Lancet 2013 382 339 352 23727170
  99. [130]Schnabel R Blankenberg S Oxidative stress in cardiovascular disease: Successful translation from bench to bedside? Circulation 2007 116 1338 1340 17875978
  100. [131]Vaziri ND Wong J Pahl M Piceno YM Yuan J DeSantis TZ Ni Z Nguyen TH Andersen GL Chronic kidney disease alters intestinal microbial flora Kidney Int 2013 83 308 315 22992469
  101. [132]Wong J Piceno YM Desantis TZ Pahl M Andersen GL Vaziri ND Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in esrd Am J Nephrol 2014 39 230 237 24643131 PMC4049264
  102. [133]Szeto CC Kwan BC Chow KM Lai KB Chung KY Leung CB Li PK Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients Clin J Am Soc Nephrol 2008 3 431 436 18256376 PMC2390956
  103. [134]Shi K Wang F Jiang H Liu H Wei M Wang Z Xie L Gut bacterial translocation may aggravate microinflammation in hemodialysis patients Dig Dis Sci 2014 59 2109 2117 24828917
  104. [135]Meijers BK Claes K Bammens B de Loor H Viaene L Verbeke K Kuypers D Vanrenterghem Y Evenepoel P P-cresol and cardiovascular risk in mild-to-moderate kidney disease Clin J Am Soc Nephrol 2010 5 1182 1189 20430946 PMC2893077
  105. [136]Koppe L Pillon NJ Vella RE Croze ML Pelletier CC Chambert S Massy Z Glorieux G Vanholder R Dugenet Y Soula HA Fouque D Soulage CO P-cresyl sulfate promotes insulin resistance associated with ckd J Am Soc Nephrol 2013 24 88 99 23274953 PMC3537215
  106. [137]Barreto FC Barreto DV Liabeuf S Meert N Glorieux G Temmar M Choukroun G Vanholder R Massy ZA Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients Clin J Am Soc Nephrol 2009 4 1551 1558 19696217 PMC2758258
  107. [138]Devlin AS Marcobal A Dodd D Nayfach S Plummer N Meyer T Pollard KS Sonnenburg JL Fischbach MA Modulation of a circulating uremic solute via rational genetic manipulation of the gut microbiota Cell Host Microbe 2016 20 709 715 27916477 PMC5159218
  108. [139]Wang CP Lu LF Yu TH Hung WC Chiu CA Chung FM Yeh LR Chen HJ Lee YJ Houng JY Serum levels of total p-cresylsulphate are associated with angiographic coronary atherosclerosis severity in stable angina patients with early stage of renal failure Atherosclerosis 2010 211 579 583 20427046
  109. [140]Rhee EP Clish CB Ghorbani A Larson MG Elmariah S McCabe E Yang Q Cheng S Pierce K Deik A Souza AL Farrell L Domos C Yeh RW Palacios I Rosenfield K Vasan RS Florez JC Wang TJ Fox CS Gerszten RE A combined epidemiologic and metabolomic approach improves ckd prediction J Am Soc Nephrol 2013 24 1330 1338 23687356 PMC3736702
  110. [141]Colman RJ Rubin DT Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis J Crohns Colitis 2014 8 1569 1581 25223604 PMC4296742
  111. [142]Brandt LJ Aroniadis OC Mellow M Kanatzar A Kelly C Park T Stollman N Rohlke F Surawicz C Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent clostridium difficile infection Am J Gastroenterol 2012 107 1079 1087 22450732
  112. [143]van Nood E Vrieze A Nieuwdorp M Fuentes S Zoetendal EG de Vos WM Visser CE Kuijper EJ Bartelsman JF Tijssen JG Speelman P Dijkgraaf MG Keller JJ Duodenal infusion of donor feces for recurrent clostridium difficile N Engl J Med 2013 368 407 415 23323867
  113. [146]Brandt LJ Fmt: First step in a long journey Am J Gastroenterol 2013 108 1367 1368 23912409
  114. [148]Wymore Brand M Wannemuehler MJ Phillips GJ Proctor A Overstreet AM Jergens AE Orcutt RP Fox JG The altered schaedler flora: Continued applications of a defined murine microbial community ILAR J 2015 56 169 178 26323627 PMC4554250
  115. [149]Appel LJ Moore TJ Obarzanek E Vollmer WM Svetkey LP Sacks FM Bray GA Vogt TM Cutler JA Windhauser MM Lin PH Karanja N A clinical trial of the effects of dietary patterns on blood pressure. Dash collaborative research group N Engl J Med 1997 336 1117 1124 9099655
  116. [150]Estruch R Ros E Salas-Salvado J Covas MI Corella D Aros F Gomez-Gracia E Ruiz-Gutierrez V Fiol M Lapetra J Lamuela-Raventos RM Serra-Majem L Pinto X Basora J Munoz MA Sorli JV Martinez JA Martinez-Gonzalez MA Primary prevention of cardiovascular disease with a mediterranean diet N Engl J Med 2013 368 1279 1290 29897867
  117. [151]Zeevi D Korem T Zmora N Israeli D Rothschild D Weinberger A Ben-Yacov O Lador D Avnit-Sagi T Lotan-Pompan M Suez J Mahdi JA Matot E Malka G Kosower N Rein M Zilberman-Schapira G Dohnalova L Pevsner-Fischer M Bikovsky R Halpern Z Elinav E Segal E Personalized nutrition by prediction of glycemic responses Cell 2015 163 1079 1094 26590418
  118. [152]Xu Z Knight R Dietary effects on human gut microbiome diversity Br J Nutr 2015 113 Suppl S1 5 PMC4405705 25498959
  119. [153]Voreades N Kozil A Weir TL Diet and the development of the human intestinal microbiome Front Microbiol 2014 5 494 25295033 PMC4170138
  120. [154]Ravussin Y Koren O Spor A LeDuc C Gutman R Stombaugh J Knight R Ley RE Leibel RL Responses of gut microbiota to diet composition and weight loss in lean and obese mice Obesity (Silver Spring) 2012 20 738 747 21593810 PMC3871199
  121. [156]Duncan SH Belenguer A Holtrop G Johnstone AM Flint HJ Lobley GE Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces Appl Environ Microbiol 2007 73 1073 1078 17189447 PMC1828662
  122. [157]Duncan SH Lobley GE Holtrop G Ince J Johnstone AM Louis P Flint HJ Human colonic microbiota associated with diet, obesity and weight loss Int J Obes (Lond) 2008 32 1720 1724 18779823
  123. [158]Foye OT Huang IF Chiou CC Walker WA Shi HN Early administration of probiotic lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and smad 7 cell signaling FEMS Immunol Med Microbiol 2012 65 467 480 22524476 PMC4015462
  124. [160]Xiao S Fei N Pang X Shen J Wang L Zhang B Zhang M Zhang X Zhang C Li M Sun L Xue Z Wang J Feng J Yan F Zhao N Liu J Long W Zhao L A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome FEMS Microbiol Ecol 2014 87 357 367 24117923 PMC4255291
  125. [161]den Besten G Bleeker A Gerding A van Eunen K Havinga R van Dijk TH Oosterveer MH Jonker JW Groen AK Reijngoud DJ Bakker BM Short-chain fatty acids protect against high-fat diet-induced obesity via a ppargamma-dependent switch from lipogenesis to fat oxidation Diabetes 2015 64 2398 2408 25695945
  126. [162]Frost G Sleeth ML Sahuri-Arisoylu M Lizarbe B Cerdan S Brody L Anastasovska J Ghourab S Hankir M Zhang S Carling D Swann JR Gibson G Viardot A Morrison D Louise Thomas E Bell JD The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism Nat Commun 2014 5 3611 24781306 PMC4015327
  127. [163]Shoaie S Ghaffari P Kovatcheva-Datchary P Mardinoglu A Sen P Pujos-Guillot E de Wouters T Juste C Rizkalla S Chilloux J Hoyles L Nicholson JK Dore J Dumas ME Clement K Backhed F Nielsen J Quantifying diet-induced metabolic changes of the human gut microbiome Cell Metab 2015 22 320 331 26244934
  128. [164]Ojetti V Lauritano EC Barbaro F Migneco A Ainora ME Fontana L Gabrielli M Gasbarrini A Rifaximin pharmacology and clinical implications Expert Opin Drug Metab Toxicol 2009 5 675 682 19442033
  129. [166]Simon MC Strassburger K Nowotny B Kolb H Nowotny P Burkart V Zivehe F Hwang JH Stehle P Pacini G Hartmann B Holst JJ MacKenzie C Bindels LB Martinez I Walter J Henrich B Schloot NC Roden M Intake of lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: A proof of concept Diabetes Care 2015 38 1827 1834 26084343
  130. [167]Simenhoff ML Dunn SR Zollner GP Fitzpatrick ME Emery SM Sandine WE Ayres JW Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried lactobacillus acidophilus Miner Electrolyte Metab 1996 22 92 96 8676836
  131. [168]Karlsson C Ahrne S Molin G Berggren A Palmquist I Fredrikson GN Jeppsson B Probiotic therapy to men with incipient arteriosclerosis initiates increased bacterial diversity in colon: A randomized controlled trial Atherosclerosis 2010 208 228 233 19608185
  132. [170]Lalles JP Intestinal alkaline phosphatase: Multiple biological roles in maintenance of intestinal homeostasis and modulation by diet Nutr Rev 2010 68 323 332 20536777
  133. [172]Cani PD Neyrinck AM Fava F Knauf C Burcelin RG Tuohy KM Gibson GR Delzenne NM Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia Diabetologia 2007 50 2374 2383 17823788
  134. [173]Robertson MD Bickerton AS Dennis AL Vidal H Frayn KN Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism Am J Clin Nutr 2005 82 559 567 16155268
  135. [174]Parnell JA Reimer RA Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide yy in overweight and obese adults Am J Clin Nutr 2009 89 1751 1759 19386741 PMC3827013
  136. [175]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 Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice Diabetes 2011 60 2775 2786 21933985 PMC3198091
  137. [176]Dewulf EM Cani PD Claus SP Fuentes S Puylaert PG Neyrinck AM Bindels LB de Vos WM Gibson GR Thissen JP Delzenne NM Insight into the prebiotic concept: Lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women Gut 2013 62 1112 1121 23135760 PMC3711491
  138. [177]Salonen A Lahti L Salojarvi J Holtrop G Korpela K Duncan SH Date P Farquharson F Johnstone AM Lobley GE Louis P Flint HJ de Vos WM Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men ISME J 2014 8 2218 2230 24763370 PMC4992075
  139. [178]Trasande L Blustein J Liu M Corwin E Cox LM Blaser MJ Infant antibiotic exposures and early-life body mass Int J Obes (Lond) 2013 37 16 23 22907693 PMC3798029
  140. [179]Cho I Yamanishi S Cox L Methe BA Zavadil J Li K Gao Z Mahana D Raju K Teitler I Li H Alekseyenko AV Blaser MJ Antibiotics in early life alter the murine colonic microbiome and adiposity Nature 2012 488 621 626 22914093 PMC3553221
  141. [181]Pluznick J A novel scfa receptor, the microbiota, and blood pressure regulation Gut Microbes 2014 5 202 207 24429443 PMC4063845
  142. [182]Holmes E Li JV Marchesi JR Nicholson JK Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk Cell Metab 2012 16 559 564 23140640
  143. [183]Turnbaugh PJ Gordon JI The core gut microbiome, energy balance and obesity J Physiol 2009 587 4153 4158 19491241 PMC2754355
  144. [185]Wu IW Hsu KH Lee CC Sun CY Hsu HJ Tsai CJ Tzen CY Wang YC Lin CY Wu MS P-cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease Nephrol Dial Transplant 2011 26 938 947 20884620 PMC3042976
  145. [186]Lin CJ Chen HH Pan CF Chuang CK Wang TJ Sun FJ Wu CJ P-cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease J Clin Lab Anal 2011 25 191 197 21567467 PMC6647585
  146. [187]Watanabe H Miyamoto Y Honda D Tanaka H Wu Q Endo M Noguchi T Kadowaki D Ishima Y Kotani S Nakajima M Kataoka K Kim-Mitsuyama S Tanaka M Fukagawa M Otagiri M Maruyama T P-cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of nadph oxidase Kidney Int 2013 83 582 592 23325087
  147. [188]Walser M Bodenlos LJ Urea metabolism in man J Clin Invest 1959 38 1617 1626 13842664 PMC293293
  148. [189]Suzuki T Heaney LM Jones DJ Ng LL Trimethylamine n-oxide and risk stratification after acute myocardial infarction Clin Chem 2017 63 420 428 28062632
  149. [191]Tang WH Wang Z Li XS Fan Y Li DS Wu Y Hazen SL Increased trimethylamine n-oxide portends high mortality risk independent of glycemic control in patients with type 2 diabetes mellitus Clin Chem 2017 63 297 306 27864387 PMC5659115
  150. [193]Tachon S Lee B Marco ML Diet alters probiotic lactobacillus persistence and function in the intestine Environ Microbiol 2014 16 2915 2926 24118739

Cited by

Sorted by citations

Authors
Tang, W. H. W., Kitai, T., & Hazen, S. L.
Affiliations
Cleveland Clinic (US)
ORCID
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-03-31
Volume
120
Issue
7
Pages
1183-1196
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/circresaha.117.309715
PMC
PMC5390330
OpenAlex
W2600254651
Cited by
1,670
References
43
Citations by year
2026: 151 · 2025: 195 · 2024: 186 · 2023: 187 · 2022: 251 · 2021: 254 · 2020: 199 · 2019: 121 · 2018: 94 · 2017: 31
FWCI
11.42
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL126827, P20HL113452, R01HL103866)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106000)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords
gut microbiota, cardiovascular disease, dysbiosis, atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, type 2 diabetes, trimethylamine N-oxide, short-chain fatty acids, bile acids, bacterial translocation, intestinal barrier function, gut microbiota metabolites, microbiota-host interactions, therapeutic target
MeSH terms
Gastrointestinal Microbiome, Animals, Cardiovascular Diseases, Diabetes Mellitus, Humans

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review