Abstract
The interaction between diet, microbiome, and noncommunicable disease onset is gaining growing attention. The trimethylamine N-oxide (TMAO) is a gut microbiota derivative that has been suggested as a potential regulator of human health, especially (but not exclusively) for its association with cardiovascular diseases. It derives from the trimethylamine (TMA), which is produced by the gut microbiome from dietary precursors, such as choline, betaine, and L-carnitine. Due to the potentially harmful effects of TMAO, strategies aimed to reduce circulating TMAO levels (ranging from dietary restrictions or supplementation to pharmacological treatments) have been proposed. Moreover, TMAO has been suggested as a biomarker of disease onset and prognosis. Nevertheless, contrasting evidence can be found in the literature, and mechanistic explanations or causal demonstrations of the association between the TMA/TMAO metabolism and diseases are still missing. Thus, despite promising findings, the history of TMAO might be more complex than initially hypothesized, and further studies are necessary to promote their translation into clinical practice.
Abbreviations
- CKD:
-
Chronic kidney diseases
- CVD:
-
Cardiovascular disease
- FMO:
-
Flavin monooxygenases
- MetS:
-
Metabolic syndrome
- NAFLD:
-
Nonalcoholic fatty liver disease
- NCD:
-
Noncommunicable disease
- STEMI:
-
ST-segment elevation myocardial infarction
- TMA:
-
Trimethylamine
- TMAO:
-
Trimethylamine N-oxide
References
Abbasalizad Farhangi M, Vajdi M. Gut microbiota-associated trimethylamine N-oxide and increased cardiometabolic risk in adults: a systematic review and dose-response meta-analysis. Nutr Rev. 2020. https://doi.org/10.1093/nutrit/nuaa111.
Anders H-J, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int. 2013;83(6):1010–6. https://doi.org/10.1038/ki.2012.440.
Andraos S, et al. Plasma trimethylamine N-oxide and its precursors: population epidemiology, parent–child concordance, and associations with reported dietary intake in 11- to 12-year-old children and their parents. Curr Dev Nutr. 2020;4(7). https://doi.org/10.1093/cdn/nzaa103.
Argyridou S, et al. Associations between physical activity and trimethylamine N-oxide in those at risk of type 2 diabetes. BMJ Open Diabetes Res Care. 2020;8(2). https://doi.org/10.1136/bmjdrc-2020-001359.
Bain MA, Fornasini G, Evans AM. Trimethylamine: metabolic, pharmacokinetic and safety aspects. Curr Drug Metab. 2005;6(3):227–40. https://doi.org/10.2174/1389200054021807.
Barrea L, et al. Trimethylamine-N-oxide (TMAO) as novel potential biomarker of early predictors of metabolic syndrome. Nutrients. 2018;10(12). https://doi.org/10.3390/nu10121971.
Beaglehole R, et al. Priority actions for the non-communicable disease crisis. Lancet (London, England). 2011;377(9775):1438–47. https://doi.org/10.1016/S0140-6736(11)60393-0.
Bennett BJ, et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013;17(1):49–60. https://doi.org/10.1016/j.cmet.2012.12.011.
Bordoni L, et al. A pilot study on the effects of L-carnitine and trimethylamine-N-oxide on platelet mitochondrial DNA methylation and CVD biomarkers in aged women. Int J Mol Sci. 2020a;21(3). https://doi.org/10.3390/ijms21031047.
Bordoni L, et al. Trimethylamine N-oxide and the reverse cholesterol transport in cardiovascular disease: a cross-sectional study. Sci Rep. 2020b;10(1):18675.
Brugère J-F, et al. Archaebiotics: proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease. Gut Microbes. 2014;5(1):5–10. https://doi.org/10.4161/gmic.26749.
Canyelles M, et al. Trimethylamine N-oxide: a link among diet, gut microbiota, gene regulation of liver and intestine cholesterol homeostasis and HDL function. Int J Mol Sci. 2018;19(10):3228. https://doi.org/10.3390/ijms19103228.
Cashman JR, et al. In vitro and in vivo inhibition of human flavin-containing monooxygenase form 3 (FMO3) in the presence of dietary indoles. Biochem Pharmacol. 1999;58(6):1047–55. https://doi.org/10.1016/s0006-2952(99)00166-5.
Chen K, et al. Gut microbiota-dependent metabolite trimethylamine N-oxide contributes to cardiac dysfunction in Western diet-induced obese mice. Front Physiol. 2017;8:139. https://doi.org/10.3389/fphys.2017.00139.
Chen L, et al. Changes in the concentrations of trimethylamine N-oxide (TMAO) and its precursors in patients with amyotrophic lateral sclerosis. Sci Rep. 2020a;10(1):15198. https://doi.org/10.1038/s41598-020-72184-3.
Chen S, et al. Effects of probiotic supplementation on serum trimethylamine-N-oxide level and gut microbiota composition in young males: a double-blinded randomized controlled trial. Eur J Nutr. 2020b. https://doi.org/10.1007/s00394-020-02278-1.
Cho CE, et al. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: a randomized controlled trial. Mol Nutr Food Res. 2017;61(1). https://doi.org/10.1002/mnfr.201600324.
Collins HL, et al. L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(−/−) transgenic mice expressing CETP. Atherosclerosis. 2016;244:29–37. https://doi.org/10.1016/j.atherosclerosis.2015.10.108.
Dannenberg L, et al. Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy. Pharmacol Ther. 2020;213:107584. https://doi.org/10.1016/j.pharmthera.2020.107584.
Dehghan P, et al. Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) potentially increases the risk of obesity in adults: an exploratory systematic review and dose-response meta- analysis. Obes Rev. 2020;21(5):e12993. https://doi.org/10.1111/obr.12993.
Del Rio D, et al. The gut microbial metabolite trimethylamine-N-oxide is present in human cerebrospinal fluid. Nutrients. 2017;9(10). https://doi.org/10.3390/nu9101053.
Dolphin CT, et al. Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome. Nat Genet. 1997;17(4):491–4. https://doi.org/10.1038/ng1297-491.
Drapala A, et al. Heart failure disturbs gut-blood barrier and increases plasma trimethylamine, a toxic bacterial metabolite. Int J Mol Sci. 2020;21(17). https://doi.org/10.3390/ijms21176161.
Fadhlaoui K, et al. Archaea, specific genetic traits, and development of improved bacterial live biotherapeutic products: another face of next-generation probiotics. Appl Microbiol Biotechnol. 2020;104(11):4705–16. https://doi.org/10.1007/s00253-020-10599-8.
Falony G, Vieira-Silva S, Raes J. Microbiology meets big data: the case of gut microbiota-derived trimethylamine. Annu Rev Microbiol. 2015;69:305–21. https://doi.org/10.1146/annurev-micro-091014-104422.
Farhangi MA, Vajdi M. Novel findings of the association between gut microbiota-derived metabolite trimethylamine N-oxide and inflammation: results from a systematic review and dose-response meta-analysis. Crit Rev Food Sci Nutr. 2020;60(16):2801–23. https://doi.org/10.1080/10408398.2020.1770199.
Farhangi MA, Vajdi M, Asghari-Jafarabadi M. Gut microbiota-associated metabolite trimethylamine N-oxide and the risk of stroke: a systematic review and dose-response meta-analysis. Nutr J. 2020;19(1):76. https://doi.org/10.1186/s12937-020-00592-2.
Fogelman AM. TMAO is both a biomarker and a renal toxin. Circ Res. 2015;116(3):396–7. https://doi.org/10.1161/CIRCRESAHA.114.305680.
Gao Q, et al. Decreased levels of circulating trimethylamine N-oxide alleviate cognitive and pathological deterioration in transgenic mice: a potential therapeutic approach for Alzheimer’s disease. Aging. 2019;11(19):8642–63. https://doi.org/10.18632/aging.102352.
Gao J, et al. Gut microbial taxa as potential predictive biomarkers for acute coronary syndrome and post-STEMI cardiovascular events. Sci Rep. 2020;10(1):2639. https://doi.org/10.1038/s41598-020-59235-5.
Gawrys-Kopczynska M, et al. TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats. eLife. 2020;9. https://doi.org/10.7554/eLife.57028.
Gencer B, et al. Gut microbiota-dependent trimethylamine N-oxide and cardiovascular outcomes in patients with prior myocardial infarction: a nested case control study from the PEGASUS-TIMI 54 trial. J Am Heart Assoc. 2020;9(10):e015331. https://doi.org/10.1161/JAHA.119.015331.
Gentile CL, Weir TL. The gut microbiota at the intersection of diet and human health. Science (New York, NY). 2018;362(6416):776–80. https://doi.org/10.1126/science.aau5812.
Ghaly AE, et al. Fish spoilage mechanisms and preservation techniques: review. Am J Appl Sci. 2010;7(7 SE-Research Article). https://doi.org/10.3844/ajassp.2010.859.877.
Govindarajulu M, et al. Gut metabolite TMAO induces synaptic plasticity deficits by promoting endoplasmic reticulum stress. Front Mol Neurosci. 2020;13:138. https://doi.org/10.3389/fnmol.2020.00138.
Hamaya R, et al. Association of diet with circulating trimethylamine-N-oxide concentration. Am J Clin Nutr. 2020;112(6):1448–55. https://doi.org/10.1093/ajcn/nqaa225.
He M, et al. Gut microbiota-derived trimethylamine-N-oxide: a bridge between dietary fatty acid and cardiovascular disease? Food Res Int (Ottawa, ON). 2020;138(Pt B):109812. https://doi.org/10.1016/j.foodres.2020.109812.
Heianza Y, et al. 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. 2017;6(7). https://doi.org/10.1161/JAHA.116.004947.
Heng X, Liu W, Chu W. Identification of choline-degrading bacteria from healthy human feces and used for screening of trimethylamine (TMA)-lyase inhibitors. Microb Pathog. 2020:104658. https://doi.org/10.1016/j.micpath.2020.104658.
Hochstrasser SR, et al. Trimethylamine-N-oxide (TMAO) predicts short- and long-term mortality and poor neurological outcome in out-of-hospital cardiac arrest patients. Clin Chem Lab Med. 2020. https://doi.org/10.1515/cclm-2020-0159.
Jameson E, et al. Metagenomic data-mining reveals contrasting microbial populations responsible for trimethylamine formation in human gut and marine ecosystems. Microb Genom. 2016;2(9):e000080. https://doi.org/10.1099/mgen.0.000080.
Janeiro MH, et al. Implication of trimethylamine N-oxide (TMAO) in disease: potential biomarker or new therapeutic target. Nutrients. 2018;10(10). https://doi.org/10.3390/nu10101398.
Jaworska K, Bielinska K, et al. TMA (trimethylamine), but not its oxide TMAO (trimethylamine-oxide), exerts haemodynamic effects: implications for interpretation of cardiovascular actions of gut microbiome. Cardiovasc Res. 2019a;115(14):1948–9. https://doi.org/10.1093/cvr/cvz231.
Jaworska K, Hering D, et al. TMA, a forgotten uremic toxin, but not TMAO, is involved in cardiovascular pathology. Toxins. 2019b;11(9). https://doi.org/10.3390/toxins11090490.
Jia J, et al. Assessment of causal direction between gut microbiota-dependent metabolites and cardiometabolic health: a bidirectional Mendelian randomization analysis. Diabetes. 2019;68(9):1747–55. https://doi.org/10.2337/db19-0153.
Koeth RA, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576–85. https://doi.org/10.1038/nm.3145.
Koeth RA, et al. γ-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metab. 2014;20(5):799–812. https://doi.org/10.1016/j.cmet.2014.10.006.
Kolluru Gopi K, Kevil Christopher G. It’s a “gut feeling”: Association of microbiota, trimethylamine N-oxide and cardiovascular outcomes. J Am Heart Assoc. 2020;9(10):e016553. https://doi.org/10.1161/JAHA.120.016553.
Laxson CJ, et al. Decreasing urea∶trimethylamine N-oxide ratios with depth in chondrichthyes: a physiological depth limit? Physiol Biochem Zool: PBZ. 2011;84(5):494–505. https://doi.org/10.1086/661774.
Li D, et al. Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice. Aging Cell. 2018;17(4):e12768. https://doi.org/10.1111/acel.12768.
Li W, et al. Gut microbiota-derived trimethylamine N-oxide is associated with poor prognosis in patients with heart failure. Med J Aust. 2020;213(8):374–9. https://doi.org/10.5694/mja2.50781.
Liang X, et al. Reduction of intestinal trimethylamine by probiotics ameliorated lipid metabolic disorders associated with atherosclerosis. Nutrition. 2020;79–80:110941. https://doi.org/10.1016/j.nut.2020.110941.
Lin H, et al. The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease. Ann Transl Med. 2020;8(16):1009. https://doi.org/10.21037/atm-20-5307.
Liu Y, et al. Gut microbiota-dependent trimethylamine N-oxide are related with hip fracture in postmenopausal women: a matched case-control study. Aging. 2020;12(11):10633–41. https://doi.org/10.18632/aging.103283.
Ma J, Pazos IM, Gai F. Microscopic insights into the protein-stabilizing effect of trimethylamine N-oxide (TMAO). Proc Natl Acad Sci. 2014;111(23):8476–81. https://doi.org/10.1073/pnas.1403224111.
Maiti A, Daschakraborty S. Effect of TMAO on the structure and phase transition of lipid membranes: potential role of TMAO in stabilizing cell membranes under osmotic stress. J Phys Chem B. 2021;125(4):1167–80. https://doi.org/10.1021/acs.jpcb.0c08335.
Mamic P, Chaikijurajai T, Tang WHW. Gut microbiome - a potential mediator of pathogenesis in heart failure and its comorbidities: state-of-the-art review. J Mol Cell Cardiol. 2020;152:105–17. https://doi.org/10.1016/j.yjmcc.2020.12.001.
Manor O, et al. A multi-omic association study of trimethylamine N-oxide. Cell Rep. 2018;24(4):935–46. https://doi.org/10.1016/j.celrep.2018.06.096.
Martin F-PJ, et al. Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. Mol Syst Biol. 2008;4:157. https://doi.org/10.1038/msb4100190.
Martínez-del Campo A, et al. Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria. mBio. 2015;6(2). https://doi.org/10.1128/mBio.00042-15.
Moludi J. et al. Probiotics supplementation on cardiac remodeling following myocardial infarction: a single-center double-blind clinical study. J Cardiovasc Transl Res. 2020. https://doi.org/10.1007/s12265-020-10052-1.
Naqvi S, et al. A cross-talk between gut microbiome, salt and hypertension. Biomed Pharmacother. 2021;134:111156. https://doi.org/10.1016/j.biopha.2020.111156.
Nowinski A, Ufnal M. Trimethylamine N-oxide: a harmful, protective or diagnostic marker in lifestyle diseases? Nutrition (Burbank, Los Angeles County, CA). 2018;46:7–12. https://doi.org/10.1016/j.nut.2017.08.001.
Obeid R, et al. Plasma trimethylamine N-oxide concentration is associated with choline, phospholipids, and methyl metabolism. Am J Clin Nutr. 2016;103(3):703–11. https://doi.org/10.3945/ajcn.115.121269.
Papandreou C, More M, Bellamine A. Trimethylamine N-oxide in relation to cardiometabolic health-cause or effect? Nutrients. 2020;12(5). https://doi.org/10.3390/nu12051330.
Pascale A, et al. Microbiota and metabolic diseases. Endocrine. 2018;61(3):357–71. https://doi.org/10.1007/s12020-018-1605-5.
Paul N, Sarkar R, Sarkar S. Zinc protoporphyrin–trimethylamine-N-oxide complex involves cholesterol oxidation causing atherosclerosis. JBIC: J Biol Inorg Chem. 2021. https://doi.org/10.1007/s00775-021-01861-z.
Qi J, et al. Circulating trimethylamine N-oxide and the risk of cardiovascular diseases: a systematic review and meta-analysis of 11 prospective cohort studies. J Cell Mol Med. 2018;22(1):185–94. https://doi.org/10.1111/jcmm.13307.
Quan L, et al. Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with autism spectrum disorders. Neurotoxicology. 2020;76:93–8. https://doi.org/10.1016/j.neuro.2019.10.012.
Rath S, et al. Uncovering the trimethylamine-producing bacteria of the human gut microbiota. Microbiome. 2017;5(1):54. https://doi.org/10.1186/s40168-017-0271-9.
Rath S, et al. Pathogenic functions of host microbiota. Microbiome. 2018;6(1):174. https://doi.org/10.1186/s40168-018-0542-0.
Rath S, et al. Potential TMA-producing bacteria are ubiquitously found in mammalia. Front Microbiol. 2020;10:2966. https://doi.org/10.3389/fmicb.2019.02966.
Roberts AB, et al. Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential. Nat Med. 2018;24(9):1407–17. https://doi.org/10.1038/s41591-018-0128-1.
Rohrmann S, et al. Plasma concentrations of trimethylamine-N-oxide are directly associated with dairy food consumption and low-grade inflammation in a German adult population. J Nutr. 2016;146(2):283–9. https://doi.org/10.3945/jn.115.220103.
Sánchez-Alcoholado L, et al. Gut microbiota-mediated inflammation and gut permeability in patients with obesity and colorectal cancer. Int J Mol Sci. 2020;21(18). https://doi.org/10.3390/ijms21186782.
Schiattarella GG, et al. Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis. Eur Heart J. 2017;38(39):2948–56. https://doi.org/10.1093/eurheartj/ehx342.
Senthong V, et al. Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. J Am Heart Assoc. 2016;5(6). https://doi.org/10.1161/JAHA.115.002816.
Simó C, García-Cañas V. Dietary bioactive ingredients to modulate the gut microbiota-derived metabolite TMAO. New opportunities for functional food development. Food Funct. 2020;11(8):6745–76. https://doi.org/10.1039/d0fo01237h.
Spence JD. Reducing the risk of stroke in patients with impaired renal function: nutritional issues. J Stroke Cerebrovasc Dis. 2020:105376. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105376.
Steinke I, et al. Drug discovery and development of novel therapeutics for inhibiting TMAO in models of atherosclerosis and diabetes. Front Physiol. 2020;11:567899. https://doi.org/10.3389/fphys.2020.567899.
Sun X, et al. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochem Biophys Res Commun. 2016;481(1–2):63–70. https://doi.org/10.1016/j.bbrc.2016.11.017.
Taesuwan S, et al. The metabolic fate of isotopically labeled trimethylamine-N-oxide (TMAO) in humans. J Nutr Biochem. 2017;45:77–82. https://doi.org/10.1016/j.jnutbio.2017.02.010.
Tanase DM, et al. Role of gut microbiota on onset and progression of microvascular complications of type 2 diabetes (T2DM). Nutrients. 2020;12(12):3719. https://doi.org/10.3390/nu12123719.
Tang WHW, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575–84. https://doi.org/10.1056/NEJMoa1109400.
Tang WHW, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116(3):448–55. https://doi.org/10.1161/CIRCRESAHA.116.305360.
Tang WHW, et al. Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(16):2089–105. https://doi.org/10.1016/j.jacc.2019.03.024.
Vaziri ND, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013;83(2):308–15. https://doi.org/10.1038/ki.2012.345.
Vogt NM, et al. The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alzheimers Res Ther. 2018;10(1):124. https://doi.org/10.1186/s13195-018-0451-2.
Wahlang B, et al. Editor’s highlight: PCB126 exposure increases risk for peripheral vascular diseases in a liver injury mouse model. Toxicol Sci. 2017;160(2):256–67. https://doi.org/10.1093/toxsci/kfx180.
Wang Z, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63. https://doi.org/10.1038/nature09922.
Wang Z, et al. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur Heart J. 2019;40(7):583–94. https://doi.org/10.1093/eurheartj/ehy799.
Wiese GN, et al. Plant-based diets, the gut microbiota, and trimethylamine N-oxide production in chronic kidney disease: therapeutic potential and methodological considerations. J Ren Nutr. 2020; https://doi.org/10.1053/j.jrn.2020.04.007.
Wu W-K, et al. Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota. J Funct Foods. 2015;15:408–17. https://doi.org/10.1016/j.jff.2015.04.001.
Wu W-K, et al. Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice. Gut. 2019;68(8):1439–49. https://doi.org/10.1136/gutjnl-2018-317155.
Wu W-K, et al. Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery. Microbiome. 2020;8(1):162. https://doi.org/10.1186/s40168-020-00912-y.
Yazaki Y, et al. Ethnic differences in association of outcomes with trimethylamine N-oxide in acute heart failure patients. ESC Heart Fail. 2020;7(5):2373–8. https://doi.org/10.1002/ehf2.12777.
Yu T, et al. Plasma trimethylamine N-oxide as a novel biomarker for plaque rupture in patients with ST-segment–elevation myocardial infarction. Circ Cardiovasc Interv. 2019;12(1):e007281. https://doi.org/10.1161/CIRCINTERVENTIONS.118.007281.
Yu Z-L, et al. Effects of dietary choline, betaine, and L-carnitine on the generation of trimethylamine-N-oxide in healthy mice. J Food Sci. 2020;85(7):2207–15. https://doi.org/10.1111/1750-3841.15186.
Yue C, et al. Trimethylamine N-oxide prime NLRP3 inflammasome via inhibiting ATG16L1-induced autophagy in colonic epithelial cells. Biochem Biophys Res Commun. 2017;490(2):541–51. https://doi.org/10.1016/j.bbrc.2017.06.075.
Zeisel SH, Warrier M. Trimethylamine N-oxide, the microbiome, and heart and kidney disease. Annu Rev Nutr. 2017;37:157–81. https://doi.org/10.1146/annurev-nutr-071816-064732.
Zerbst-Boroffka I, et al. TMAO and other organic osmolytes in the muscles of amphipods (Crustacea) from shallow and deep water of Lake Baikal. Comp Biochem Physiol A Mol Integr Physiol. 2005;142(1):58–64. https://doi.org/10.1016/j.cbpa.2005.07.008.
Zhang C, et al. Dietary modulation of gut microbiota contributes to alleviation of both genetic and simple obesity in children. EBioMedicine. 2015;2(8):968–84. https://doi.org/10.1016/j.ebiom.2015.07.007.
Zhao X, et al. Therapeutic potential of natural products against atherosclerosis: targeting on gut microbiota. Pharmacol Res. 2020:105362. https://doi.org/10.1016/j.phrs.2020.105362.
Zheng Y, et al. Trimethylamine-N-oxide is an independent risk factor for hospitalization events in patients receiving maintenance hemodialysis. Ren Fail. 2020;42(1):580–6. https://doi.org/10.1080/0886022X.2020.1781170.
Zhou W, et al. Implication of gut microbiota in cardiovascular diseases. Oxidative Med Cell Longev. 2020;2020:5394096. https://doi.org/10.1155/2020/5394096.
Zhu Y, et al. Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. Proc Natl Acad Sci U S A. 2014;111(11):4268–73. https://doi.org/10.1073/pnas.1316569111.
Zhu W, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell. 2016;165(1):111–24. https://doi.org/10.1016/j.cell.2016.02.011.
Zhu W, et al. Gut microbe-generated trimethylamine N-oxide from dietary choline is prothrombotic in subjects. Circulation. 2017;135(17):1671–3. https://doi.org/10.1161/CIRCULATIONAHA.116.025338.
Zhu C, et al. Whole egg consumption increases plasma choline and betaine without affecting TMAO levels or gut microbiome in overweight postmenopausal women. Nutr Res (New York, NY). 2020;78:36–41. https://doi.org/10.1016/j.nutres.2020.04.002.
Zhuang R, et al. Gut microbe–generated metabolite trimethylamine N-oxide and the risk of diabetes: a systematic review and dose-response meta-analysis. Obes Rev. 2019;20(6):883–94. https://doi.org/10.1111/obr.12843.
Zhuang Z, et al. Causal relationships between gut metabolites and Alzheimer’s disease: a bidirectional Mendelian randomization study. Neurobiol Aging. 2020. https://doi.org/10.1016/j.neurobiolaging.2020.10.022.
Zuo K, et al. Metagenomic data-mining reveals enrichment of trimethylamine-N-oxide synthesis in gut microbiome in atrial fibrillation patients. BMC Genomics. 2020;21(1):526. https://doi.org/10.1186/s12864-020-06944-w.
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Gabbianelli, R., Bordoni, L. (2022). Trimethylamine N-Oxide (TMAO) as a Biomarker. In: Patel, V.B., Preedy, V.R. (eds) Biomarkers in Nutrition . Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-81304-8_2-1
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