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2000
Volume 23, Issue 3
  • ISSN: 1570-1611
  • E-ISSN: 1875-6212

Abstract

Background

Gut microbiota-derived metabolite Trimethylamine-N-oxide (TMAO) is increasingly recognized as a potential novel prognostic biomarker for cardiovascular disease. Our research work aimed to investigate the potential utility of TMAO measurement in patients with ST-elevation Myocardial Infarction (STEMI).

Methods

We performed a systematic literature search in PubMed from inception to the 1st of February 2024 to identify all studies examining the association between plasma TMAO levels and disease complexity or clinical outcomes in STEMI patients.

Results

A total of eight prospective cohort studies were included, encompassing a total of 2,378 STEMI patients. Three of the studies provided only in-hospital evidence (., increased odds for more severe coronary artery disease, plaque rupture, and plaque healing in patients with increased TMAO levels). Four studies examined the long-term prognostic value of TMAO after 10-12 months of follow-up post-STEMI (., increased risk of adverse cardiovascular events in patients with increased TMAO levels), while one study provided data for both in-hospital and mid-term prognosis, indicating that 4-months after STEMI patients with greater TMAO elevation had larger infarct size.

Conclusion

Higher TMAO levels were associated with a greater prevalence of high-risk coronary plaque characteristics and worse in-hospital and follow-up outcomes in STEMI patients. Further study is needed on whether modulating the diet-dependent TMAO levels could improve clinical outcomes in these patients.

Registration Number

[(OSF): https://doi.org/10.17605/OSF.IO/WNG8V].

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References

  1. WitkowskiM. WeeksT.L. HazenS.L. Gut microbiota and cardiovascular disease.Circ. Res.2020127455357010.1161/CIRCRESAHA.120.316242 32762536
    [Google Scholar]
  2. WangZ. KlipfellE. BennettB.J. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease.Nature20114727341576310.1038/nature09922 21475195
    [Google Scholar]
  3. SchiattarellaG.G. SanninoA. ToscanoE. Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: A systematic review and dose-response meta-analysis.Eur. Heart J.201738392948295610.1093/eurheartj/ehx342 29020409
    [Google Scholar]
  4. HeianzaY. MaW. MansonJ.E. RexrodeK.M. QiL. Gut microbiota metabolites and risk of major adverse cardiovascular disease events and death: A systematic review and meta‐analysis of prospective studies.J. Am. Heart Assoc.201767e00494710.1161/JAHA.116.004947 28663251
    [Google Scholar]
  5. PageM.J. McKenzieJ.E. BossuytP.M. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.BMJ202137271n7110.1136/bmj.n71 33782057
    [Google Scholar]
  6. GrootenW.J.A. TseliE. ÄngB.O. Elaborating on the assessment of the risk of bias in prognostic studies in pain rehabilitation using QUIPS—aspects of interrater agreement.Diagn. Progn. Res.201931510.1186/s41512‑019‑0050‑0 31093575
    [Google Scholar]
  7. AldujeliA. PatelR. GrabauskyteI. The impact of trimethylamine N-Oxide and coronary microcirculatory dysfunction on outcomes following ST-elevation myocardial infarction.J. Cardiovasc. Dev. Dis.202310519710.3390/jcdd10050197 37233164
    [Google Scholar]
  8. AlmesnedM.A. PrinsF.M. LipšicE. Temporal course of plasma trimethylamine N-oxide (TMAO) levels in ST-elevation myocardial infarction.J. Clin. Med.20211023567710.3390/jcm10235677 34884379
    [Google Scholar]
  9. MatsuzawaY. NakahashiH. KonishiM. Microbiota-derived trimethylamine N-oxide predicts cardiovascular risk after STEMI.Sci. Rep.2019911164710.1038/s41598‑019‑48246‑6 31406181
    [Google Scholar]
  10. TanY. ShengZ. ZhouP. Plasma trimethylamine N-oxide as a novel biomarker for plaque rupture in patients with ST-segment–elevation myocardial infarction.Circ. Cardiovasc. Interv.2019121e00728110.1161/CIRCINTERVENTIONS.118.007281 30599768
    [Google Scholar]
  11. ShengZ. TanY. LiuC. Relation of circulating trimethylamine N-oxide with coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction.Am. J. Cardiol.2019123689489810.1016/j.amjcard.2018.12.018 30594289
    [Google Scholar]
  12. GaoJ. YanK.T. WangJ.X. Gut microbial taxa as potential predictive biomarkers for acute coronary syndrome and post-STEMI cardiovascular events.Sci. Rep.2020101263910.1038/s41598‑020‑59235‑5 32060329
    [Google Scholar]
  13. LiJ. ShengZ. TanY. Association of plasma trimethylamine N-Oxide level with healed culprit plaques examined by optical coherence tomography in patients with ST-Segment elevation myocardial infarction.Nutr. Metab. Cardiovasc. Dis.202131114515210.1016/j.numecd.2020.06.016 33500103
    [Google Scholar]
  14. ZhaoS. TianY. WangS. Prognostic value of gut microbiota-derived metabolites in patients with ST-segment elevation myocardial infarction.Am. J. Clin. Nutr.2023117349950810.1016/j.ajcnut.2022.12.013 36811471
    [Google Scholar]
  15. SelineK. JoheinH. The determination of l-carnitine in several food samples.Food Chem.2007105279380410.1016/j.foodchem.2007.01.058
    [Google Scholar]
  16. PattersonK.K. BhagwatS.A. WilliamsJ. HoweJ.C. HoldenJ.M. USDA database for the choline content of common foods, release two.2007Available from https://www.ars.usda.gov/research/publications/publication/?seqNo115=221425
  17. StremmelW. SchmidtK.V. SchuhmannV. Blood trimethylamine-N-oxide originates from microbiota mediated breakdown of phosphatidylcholine and absorption from small intestine.PLoS One2017121e017074210.1371/journal.pone.0170742 28129384
    [Google Scholar]
  18. BennettB.J. VallimT.Q.A. WangZ. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation.Cell Metab.2013171496010.1016/j.cmet.2012.12.011 23312283
    [Google Scholar]
  19. CanyellesM. BorràsC. RotllanN. TondoM. Escolà-GilJ.C. Blanco-VacaF. Gut microbiota-derived TMAO: A causal factor promoting atherosclerotic cardiovascular disease?Int. J. Mol. Sci.2023243194010.3390/ijms24031940 36768264
    [Google Scholar]
  20. KoethR.A. WangZ. LevisonB.S. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis.Nat. Med.201319557658510.1038/nm.3145 23563705
    [Google Scholar]
  21. BoulangerC.M. Endothelium.Arterioscler. Thromb. Vasc. Biol.2016364e26e3110.1161/ATVBAHA.116.306940 27010027
    [Google Scholar]
  22. SinghG.B. ZhangY. BoiniK.M. KokaS. High mobility group box 1 mediates TMAO-induced endothelial dysfunction.Int. J. Mol. Sci.20192014357010.3390/ijms20143570 31336567
    [Google Scholar]
  23. ChouR.H. ChenC.Y. ChenI.C. Trimethylamine N-oxide, circulating endothelial progenitor cells, and endothelial function in patients with stable angina.Sci. Rep.201991424910.1038/s41598‑019‑40638‑y 30862856
    [Google Scholar]
  24. MaG. PanB. ChenY. Trimethylamine N-oxide in atherogenesis: Impairing endothelial self-repair capacity and enhancing monocyte adhesion.Biosci. Rep.2017372BSR2016024410.1042/BSR20160244 28153917
    [Google Scholar]
  25. BruntV.E. Gioscia-RyanR.A. CassoA.G. Trimethylamine-N-oxide promotes age-related vascular oxidative stress and endothelial dysfunction in mice and healthy humans.Hypertension202076110111210.1161/HYPERTENSIONAHA.120.14759 32520619
    [Google Scholar]
  26. SeldinM.M. MengY. QiH. Trimethylamine N‐oxide promotes vascular inflammation through signaling of mitogen‐activated protein kinase and nuclear factor‐κB.J. Am. Heart Assoc.201652e00276710.1161/JAHA.115.002767 26903003
    [Google Scholar]
  27. ZhuW. BuffaJ.A. WangZ. Flavin monooxygenase 3, the host hepatic enzyme in the metaorganismal trimethylamine N‐oxide‐generating pathway, modulates platelet responsiveness and thrombosis risk.J. Thromb. Haemost.20181691857187210.1111/jth.14234 29981269
    [Google Scholar]
  28. WitkowskiM. WitkowskiM. FriebelJ. Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis.Cardiovasc. Res.2022118102367238410.1093/cvr/cvab263 34352109
    [Google Scholar]
  29. ChambersE.S. PrestonT. FrostG. MorrisonD.J. Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health.Curr. Nutr. Rep.20187419820610.1007/s13668‑018‑0248‑8 30264354
    [Google Scholar]
  30. CatryE. BindelsL.B. TailleuxA. Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction.Gut201867227128310.1136/gutjnl‑2016‑313316 28377388
    [Google Scholar]
  31. PapazoglouA.S. Microbially produced imidazole propionate is associated with heart failure and mortality.JACC Heart Fail.16502023111110.1016/j.jchf.2023.08.024 37940221
    [Google Scholar]
  32. ArabiS.M. BahramiL.S. RahnamaI. SahebkarA. Impact of synbiotic supplementation on cardiometabolic and anthropometric indices in patients with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.Pharmacol. Res.202217610606110.1016/j.phrs.2022.106061 34999222
    [Google Scholar]
  33. BartolomaeusH. AveryE.G. BartolomaeusT.U.P. Blood pressure changes correlate with short-chain fatty acid production potential shifts under a synbiotic intervention.Cardiovasc. Res.202011671252125310.1093/cvr/cvaa083 32232443
    [Google Scholar]
  34. KhaliliL. CentnerA.M. SalazarG. Effects of berries, phytochemicals, and probiotics on atherosclerosis through gut microbiota modification: A meta-analysis of animal studies.Int. J. Mol. Sci.2023244308410.3390/ijms24043084 36834497
    [Google Scholar]
  35. ShenR. ChenS. LeiW. ShenJ. LvL. WeiT. Nonfood probiotic, prebiotic, and synbiotic use reduces all-cause and cardiovascular mortality risk in older adults: A population-based cohort study.J. Nutr. Health Aging202327539139710.1007/s12603‑023‑1921‑1 37248763
    [Google Scholar]
  36. NeverovskyiA. ChernyavskyiV. ShypulinV. Probiotic Lactobacillus plantarum may reduce cardiovascular risk: An experimental study.ARYA Atheroscler.2021174110 35685234
    [Google Scholar]
  37. SunB. MaT. LiY. Bifidobacterium lactis probio-M8 adjuvant treatment confers added benefits to patients with coronary artery disease via target modulation of the gut-heart/-brain axes.mSystems202272e00100e0012210.1128/msystems.00100‑22 35343796
    [Google Scholar]
  38. SohouliM.H. OzovanuO.D. FatahiS. HekmatdoostA. Impact of probiotic supplementation on trimethylamine N-oxide (TMAO) in humans: A systematic review and meta-analysis of randomized controlled trials.Clin. Nutr. ESPEN202250566210.1016/j.clnesp.2022.06.006 35871952
    [Google Scholar]
  39. MiaoL. DuJ. ChenZ. ShiD. QuH. Effects of microbiota-driven therapy on circulating trimethylamine-N-oxide metabolism: A systematic review and meta-analysis.Front. Cardiovasc. Med.2021871056710.3389/fcvm.2021.710567 34552967
    [Google Scholar]
  40. Vieira-SilvaS. FalonyG. BeldaE. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis.Nature2020581780831031510.1038/s41586‑020‑2269‑x 32433607
    [Google Scholar]
  41. LiD.Y. LiX.S. ChaikijurajaiT. Relation of statin use to gut microbial trimethylamine n-oxide and cardiovascular risk.Am. J. Cardiol.2022178263410.1016/j.amjcard.2022.05.010 35787338
    [Google Scholar]
  42. DiasA.M. CordeiroG. EstevinhoM.M. Gut bacterial microbiome composition and statin intake - A systematic review.Pharmacol. Res. Perspect.202083e0060110.1002/prp2.601 32476298
    [Google Scholar]
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  • Article Type:
    Review Article
Keyword(s): biomarker; cardiovascular disease; microbiome; risk stratification; STEMI; TMAO
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