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Trimethylamine-N-Oxide, a Metabolite Associated with Atherosclerosis, Exhibits Complex Genetic and Dietary Regulation
Open accessAbstract
Circulating trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis. We now examine genetic, dietary, and hormonal factors regulating TMAO levels. We demonstrate that two flavin mono-oxygenase family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to TMAO. Further, we show that FMO3 exhibits 10-fold higher specific activity than FMO1. FMO3 overexpression in mice significantly increases plasma TMAO levels while silencing FMO3 decreases TMAO levels. In both humans and mice, hepatic FMO3 expression is reduced in males compared to females. In mice, this reduction in FMO3 expression is due primarily to downregulation by androgens. FMO3 expression is induced by dietary bile acids by a mechanism that involves the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor. Analysis of natural genetic variation among inbred strains of mice indicates that FMO3 and TMAO are significantly correlated, and TMAO levels explain 11% of the variation in atherosclerosis.
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In the citing paper
“Intestinal microbiota convert the choline moiety of dietary phosphatidylcholine into trimethylamine, which is subsequently converted into TMAO by hepatic flavin-containing monooxygenases (Fig. 3).20–23”
From Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk (2013) · cites this paper as [23]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Intestinal microbiota convert the choline moiety of dietary phosphatidylcholine into trimethylamine, which is subsequently converted into TMAO by hepatic flavin-containing monooxygenases (Fig. 3).20–23”
From Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk (2013) · cites this paper as [20]
Experimental — accuracy not yet measuredIn the citing paper
“TMAO is derived primarily from dietary choline and carnitine through the action of gut microbiota, which metabolize these constituents to trimethylamine (TMA).1, 11, 12 TMA is absorbed in turn and travels via the portal circulation to the liver, where it is oxidized by flavin‐containing monoxygenases, primarily FMO3, to TMAO.1, 11, 12”
From Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB (2016) · cites this paper as [12]
In the citing paper
“In contrast, examination of hepatic FMO enzyme activity, which is responsible for converting TMA into TMAO (Wang et al., 2011; Bennett et al., 2013), revealed no significant differences between both donor mouse strains, and among the various recipient groups post cecal microbial transplantation (Figure S6, panel B).”
From Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk (2016) · cites this paper as Bennett et al., 2013
In the citing paper
“host hepatic FMO3, the primary FMO responsible for TMAO production”
From Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis (2015) · cites this paper as Bennett et al., 2013
In the citing paper
“important regulators in host lipid and sterol metabolism, as well as atherosclerosis development”
From Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis (2015) · cites this paper as Bennett et al., 2013
In the citing paper
“Multiple lines of evidence show the meta-organismal pathway involved in TMAO production is mechanistically linked to atherosclerosis susceptibility (Bennett et al., 2013; Gregory et al., 2015; Koeth et al., 2013; Wang et al., 2011).”
From Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis (2015) · cites this paper as Bennett et al., 2013
In the citing paper
“Further investigations revealed that TMAO levels help to explain a significant portion of atherosclerosis aortic root development across multiple different inbred strains of mice, and that TMAO levels are influenced by hepatic Fmo3, which is under complex control, including regulation by the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor (54).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [54]
In the citing paper
“Further, FMO3 overexpression in mice significantly increased plasma TMAO levels, while silencing FMO3 decreased TMAO levels (54).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [54]
In the citing paper
“The conversion from TMA to TMAO requires an oxidation step that is mediated by host enzyme machinery in the form of FMOs (54,(78)(79)(80)(81).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [54]
In the citing paper
“In both humans and mice, hepatic FMO3 expression was observed to be reduced in males compared with females (25,54) and could be induced by dietary bile acids through a mechanism that involves FXR (54).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [54]
In the citing paper
“FMO1, FMO2, and FMO3 were all capable of forming TMAO, though the specific activity of FMO3 was at least 10-fold higher than that the other FMOs (54).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [54]
In the citing paper
“Recent studies among multiple different inbred strains of mice in a “mouse diversity panel” linked variations in strain and sex to hepatic expression/activity of FMO3, TMAO levels, and atherosclerosis (54).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [54]
In the citing paper
“Gut microbe-produced TMA reaches the liver rapidly via the portal circulation, where a cluster of hepatic FMO enzymes efficiently oxidizes TMA into TMAO (54,82).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [54]
In the citing paper
“phosphatidylcholine, the major dietary source of choline, and the gut microbe-dependent metabolite, trimethylamine N -oxide (TMAO), 4 are both mechanistically linked to atherosclerosis development (5, 6, 8)”
From Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation (2015) · cites this paper as [8]
In the citing paper
“Elevated TMAO has been observed in patients with cardiovascular disease and atherosclerosis, highlighting a potential downside to increased protein intake.[15-17,22, 37]”
From The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level (2018) · cites this paper as [37]
In the citing paper
“TMAO is a small organic compound, mainly derived from choline (found in foods such as red meat, fish, poultry, and eggs), which is metabolized to produce trimethylamine (TMA) by microbiota1, 4 and then to TMAO by the hepatic enzyme, flavin monooxygenase 3.1, 5”
In the citing paper
“FMO3 has tenfold higher specific activity in the liver than does FMO1 (13).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [13]
In the citing paper
“Most TMA is absorbed into the hepatic portal circulation by passive diffusion across the enterocyte membranes and then is efficiently converted to TMAO by hepatic FMO1 and FMO3 (13); about 95% of TMA is oxidized as it is subsequently excreted in urine in a 3:95 TMA:TMAO ratio (132).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [13]
In the citing paper
“The bile salt, cholic acid, induces FMO3 via the bile acid-activated nuclear receptor FXR (13).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [13]
In the citing paper
“Thus, FMO3 activity is 100 times higher in female than in male mice; more modest gender-related differences are observed in humans (13).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [13]
In the citing paper
“TMA is formed in male ejaculate and vaginal secretions, and as noted in Section 2.2, TMA formation may be regulated by sex hormones (13), and cycle-dependent variations in TMA occur in women (82).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [13]
In the citing paper
“It retains the folded state of proteins and counteracts the effect of denaturants, such as pH, urea, and high pressure (6,13,29).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [13]
In the citing paper
“TMAO is generated via a meta-organismal pathway that begins with gut microbial conversion of dietary nutrients (e.g. phosphatidylcholine, choline, and carnitine) into trimethylamine (TMA), followed by host liver oxidation to TMAO by flavin monooxygenases (FMOs)29,30.”
From Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential (2018) · cites this paper as [30]
In the citing paper
“It has been demonstrated that the gene encoding FMO3 is a direct FXR target gene, and FXR has been found to be a target of sirtuin 1 (SIRT1) in metabolic regulation (23, 34, 35).”
In the citing paper
“It has been demonstrated that the gene encoding FMO3 is a direct FXR target gene, and FXR has been found to be a target of sirtuin 1 (SIRT1) in metabolic regulation (23, 34, 35).”
In the citing paper
“Dietary choline is metabolized by the intestinal microbiota to TMA, which is further metabolized by FMO enzymes, in particular, FMO3, to produce TMAO in the liver (23).”
In the citing paper
“Thus, it is plausible that the decreased levels of TMAO detected in sera of mice colonized with the “core plus all” community (Fig. 1C and Fig. 3A) are caused by increased microbial degradation of cholic acid, which would result in lower levels of fmo3 expression (27).”
From Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide (2015) · cites this paper as [27]
In the citing paper
“Expression of the main FMO enzyme involved in TMAO production from TMA, FMO3, is induced by bile acids via a mechanism that involves the farnesoid X receptor (FXR) (27).”
From Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide (2015) · cites this paper as [27]
In the citing paper
“consistent with previous studies in conventionally raised mice which demonstrated that FMO3 is expressed at higher levels in females than in males (8, 27).”
From Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide (2015) · cites this paper as [27]
In the citing paper
“Specifically, cholic acid stimulates FMO3 expression (27).”
From Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide (2015) · cites this paper as [27]
In the citing paper
“is downregulated by testosterone (Bennett et al., 2013)”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Bennett et al., 2013
In the citing paper
“The TMA produced is then transported to liver via the portal vein and readily metabolized by host hepatic flavin monooxygenases (FMOs) (mainly FMO376) into TMAO9.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [76]
In the citing paper
“Studies by Bennett et al. found that human liver samples from female subjects showed higher FMO1/3 expression, and therefore an increased capacity for TMAO generation, than those from males.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [76]
In the citing paper
“Likewise, gonadectomized male mice treated with testosterone show reduced hepatic FMO3 expression, while ovariectomized female mice treated with estrogen exhibit increases in hepatic FMO3 expression76.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [76]
In the citing paper
“Rodents show a significant sexual dimorphism with respect to FMO3 expression, and TMAO levels, with females showing higher levels (and greater atherosclerosis capacity9, 76).”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [76]
In the citing paper
“Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects.”
In the citing paper
“However, it is also clear that in people with adequate renal function, this rise in TMAO is transient.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [165]
In the citing paper
“Nonetheless, high dietary fish intakes, especially of deep sea (and cold water) varieties of fish, which are more likely to contain TMAO, is associated with increases in urinary TMAO excretion165.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [165]
In the citing paper
“Subsequent studies showed that TMAO is rapidly cleared from the body after ingestion157,165,191.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [165]
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Citations
Cites
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597
Self-citationRole of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678
Benson, A. K., Kelly, S. A., Legge, R., Ma, F., Low, S. J., Kim, J., Zhang, M., Oh, P. L., Nehrenberg, D., Hua, K., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007028107 · Cited by 1,314
Dumas, M.-E., Barton, R. H., Toye, A., Cloarec, O., Blancher, C., Rothwell, A., Fearnside, J., Tatoud, R., Blanc, V., Lindon, J. C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601056103 · Cited by 1,042 · cited 1×
“Numerous reports in the literature have shown that there is genetic control of the composition of gut flora (Benson et al., 2010; Dumas et al., 2006; Kovacs et al., 2011; Turnbaugh et al., 2010).”
BackgroundMapping the Genetic Architecture of Gene Expression in Human Liver
Schadt, E. E., Molony, C. M., Chudin, E., Hao, K., Yang, X., Lum, P. Y., Kasarskis, A., Zhang, B., Wang, S. S.-M., Suver, C., et al. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060107 · Cited by 918
Self-citationSensing Odorants and Pheromones with Chemosensory Receptors
Touhara, K., & Vosshall, L. B. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163209 · Cited by 585
Krueger, S. K., & Williams, D. E. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.01.001 · Cited by 570
Bhattacharyya, T. (2008) · JAMA · doi:10.1001/jama.299.11.1265 · Cited by 529
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Liu, Y., Dou, C., Wei, G., Zhang, L., Xiong, W., Wen, L., Xiang, C., Chen, C., Zhang, T., Altamirano, A. M., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1064872 · Cited by 12
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Wu, K., Yang, X. F., Zhang, T., Bai, Y., & Yan, M. (2025) · European journal of medical research · doi:10.1186/s40001-025-02824-9 · Cited by 11
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Sun, Y., Lin, X., Liu, Z., Hu, L., Sun, P., Shen, G., Fan, F., Zhang, Y., & Li, J. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1397023 · Cited by 14
Shukla, A., Sharma, C., Malik, M. Z., Singh, A. K., Aditya, A. K., Mago, P., Shalimar, S., & Ray, A. K. (2025) · Journal of Environmental Management · doi:10.1016/j.jenvman.2025.124693 · Cited by 11
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Sorokin, A. V., Kotani, K., Bushueva, O. Y., & Polonikov, A. (2015) · Cardiology in the Young · doi:10.1017/s104795111500102x · Cited by 11
Mehmood, K., Moin, A., Hussain, T., Rizvi, S. M. D., Gowda, D., Shakil, S., & Kamal, M. (2021) · Folia Microbiologica · doi:10.1007/s12223-021-00926-5 · Cited by 11
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Niizeki, N., & Tanimoto, S. (2024) · Food Reviews International · doi:10.1080/87559129.2024.2358949 · Cited by 9
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Jiang, R., Kountz, D. J., Zhang, L., & Krzycki, J. A. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108524 · Cited by 9
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He, G., Liu, X., Lu, A.-S., & Feng, Y. (2022) · Cardiovascular Therapeutics · doi:10.1155/2022/9512401 · Cited by 9
Wei, H., Zhao, M., Wu, J., Li, C., Huang, M., Gao, J., Zhang, Q., Liang, J., Wang, Y., Zhao, C., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac519 · Cited by 9
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Huang, P., Chen, D., Chen, Y., Shih, M., Lee, B., Tain, Y., Hsieh, C., & Hou, C. (2024) · Molecules · doi:10.3390/molecules29020429 · Cited by 9
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Longtine, A. G., Greenberg, N., de Quirós, Y. B., & Brunt, V. E. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00764.2023 · Cited by 9
Shimizu, M., Suemizu, H., Mizuno, S., Kusama, T., Miura, T., Uehara, S., & Yamazaki, H. (2018) · The Journal of Toxicological Sciences · doi:10.2131/jts.43.387 · Cited by 9
Bordoni, L., Fedeli, D., Piangerelli, M., Pelikant‐Małecka, I., Radulska, A., Samulak, J. J., Sawicka, A. K., Lewicki, Ł., Kalinowski, L., Olek, R. A., et al. (2020) · Biomedicines · doi:10.3390/biomedicines8080238 · Cited by 9
Zhu, K.-X., Song, P.-Y., Heli, Li, M.-P., Du, Y., Ma, Q., Peng, L., & Chen, X. (2020) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-020-03024-6 · Cited by 9
Diet-mediated metaorganismal relay biotransformation: health effects and pathways
Li, Y., Cao, H., Wang, X., Guo, L., Ding, X., Zhao, W., & Zhang, F. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.2004993 · Cited by 9
Cheema, U. B., Most, E., Eder, K., & Ringseis, R. (2019) · British Journal Of Nutrition · doi:10.1017/s0007114519000709 · Cited by 9
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Zhu, Y., Zhu, L., Wang, Z., Qiu, X., Wu, W., Liu, W.-W., Feng, Y.-Y., Xiao, W., Luo, X., Li, Z., et al. (2020) · Cardiology Research and Practice · doi:10.1155/2020/7361434 · Cited by 9
Self-citationThrombosis Prevention: Let's Drug the Microbiome!
Vinchi, F. (2019) · HemaSphere · doi:10.1097/hs9.0000000000000165 · Cited by 9
García-Fernández, H., Alcala-Diaz, J. F., Quintana‐Navarro, G. M., López-Moreno, J., Luque-Córdoba, D., Narváez, E. R.-D., Larriva, A. P. A.-D., Gutierrez-Mariscal, F. M., Torres-Peña, J. D., Rodríguez-Cano, D., et al. (2024) · The World Journal of Men s Health · doi:10.5534/wjmh.230366 · Cited by 10
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Ding, Z., Yu, Y., Wei, J., Wang, Z., Lin, R., Li, Y., & Guo, Z. (2025) · Biomolecules · doi:10.3390/biom15101447 · Cited by 8
Self-citationBerberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme
Qu, H., Zhang, Y., Shi, J., Zhao, Y., Gao, J., Gao, Z.-Y., & Shi, D. (2023) · Current Medicinal Chemistry · doi:10.2174/0929867330666230524142632 · Cited by 8
Liu, W., Ren, C., Zhang, W., Liu, G., & Lu, P. (2021) · Current Eye Research · doi:10.1080/02713683.2021.1962361 · Cited by 8
Khodabakhshi, A., Monfared, V., Arabpour, Z., Vahid, F., & Hasani, M. (2022) · Nutrition and Cancer · doi:10.1080/01635581.2022.2129080 · Cited by 8
Age and APOE affect L-carnitine system metabolites in the brain in the APOE-TR model
Huguenard, C. J. C., Cseresznye, A., Darcey, T. S., Nkiliza, A., Evans, J. E., Hazen, S. L., MULLAN, M. J., Crawford, F., & Abdullah, L. I. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1059017 · Cited by 9
Self-citationDwidar, M., Buffa, J. A., Wang, Z., Santos, A., Tittle, A. N., Fu, X., Hajjar, A. M., DiDonato, J. A., & Hazen, S. L. (2023) · mBio · doi:10.1128/mbio.00937-23 · Cited by 8
Self-citationBockus, A. B., & Seibel, B. A. (2017) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2017.12.008 · Cited by 8
Wang, D., Chen, X., Li, Z., & Luo, Y. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1158293 · Cited by 8
Integrated microbiome-metabolome-genome axis data of Laiwu and Lulai pigs
Lai, X., Zhang, Z., Zhang, Z., Liu, S., Bai, C., Chen, Z., Qadri, Q. R., Fang, Y., Wang, Z., Pan, Y., et al. (2023) · Scientific Data · doi:10.1038/s41597-023-02191-2 · Cited by 8
Self-citationJames, K. L., Gertz, E., Kirschke, C. P., Allayee, H., Huang, L., Kable, M. E., Newman, J. W. I., Stephensen, C. B., & Bennett, B. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032074 · Cited by 7
Self-citationSotgia, S. (2025) · Clinica Chimica Acta · doi:10.1016/j.cca.2025.120294 · Cited by 7
Park, H. B., Song, D., Nguyen, M. T., Palm, N. W., & Crawford, J. M. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.5c00313 · Cited by 7
Zhou, A., Peng, N., Yang, L., Yang, S., & Wang, J. (2025) · BMC Microbiology · doi:10.1186/s12866-025-04151-9 · Cited by 7
Abavisani, M., Sajjadi, S. M., Ebadpour, N., Karav, S., & Sahebkar, A. (2025) · Nutrition & Metabolism · doi:10.1186/s12986-025-01051-7 · Cited by 7
Calvillo, L., Vanoli, E., Ferrara, F., & Caradonna, E. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010203 · Cited by 7
Feng, C., He, Q., Kwok, L., & Sun, Z. (2026) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2026.105818 · Cited by 7
Marsh, K. A., Saunders, A. V., & Zeuschner, C. L. (2015) · Practice, progress, and proficiency in sustainability · doi:10.4018/978-1-4666-9553-5.ch008 · Cited by 7
Sun, X., Sun, W., Huang, Y., & Chen, J. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/7940684 · Cited by 7
Niiranen, T., Erlund, I., Jalkanen, S., Jula, A., & Salmi, M. (2022) · European Journal of Immunology · doi:10.1002/eji.202250074 · Cited by 7
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Hania, W. B., Ballet, N., Vandekerckove, P., Ollivier, B., O’Toole, P. W., & Brugère, J. (2017) · InTech eBooks · doi:10.5772/intechopen.69945 · Cited by 7
Focalization of thrombosis and therapeutic perspectives: a memoir
Keziah, S. M., & Devi, C. S. (2018) · Oriental Pharmacy and Experimental Medicine · doi:10.1007/s13596-018-0331-0 · Cited by 7
Gut microbiota: A new protagonist in the risk of cardiovascular disease?
García‐Ríos, A., García, A. C., Pérez‐Jiménez, F., & Pérez‐Martínez, P. (2019) · Clínica e Investigación en Arteriosclerosis (English Edition) · doi:10.1016/j.artere.2018.11.004 · Cited by 7
Population studies of TMAO and its precursors may help elucidate mechanisms
Meyer, K. A. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa068 · Cited by 7
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Huang, Y., Fang, R., Xiong, T., Li, W., & Yu, N. Z. (2025) · Microorganisms · doi:10.3390/microorganisms13051073 · Cited by 7
Li, R., Wang, Y., Ji, X., Han, Q., He, K., Zhao, H., & Li, H. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1597695 · Cited by 6
Emerging therapy targets to modulate microbiome-mediated effects evident in cardiovascular disease
Hoffelner, D. K., & Hendrikx, T. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1631841 · Cited by 6
Research progress of gut microbiota and its metabolites in polycystic ovary syndrome
Qin, S., Guo, S., Tan, X., Li, K., & Huang, J. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1700191 · Cited by 7
Sudi, S. D., Suresh, S. D., Kolli, T., Azamar, K. M. M., Dickson, A., Mohammadalizadeh, Z., & Porras, A. M. (2025) · Scientific Reports · doi:10.1038/s41598-025-32038-2 · Cited by 6
Chen, Y.-L., Tang, L.-C., Zhou, W., Sun, X., Lai, Z., Xu, S., Cai, K., Shi, Y., Zhao, R. Z., Zhou, X., et al. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2025.11.014 · Cited by 6
Heianza, Y., Zhou, T., He, H., DiDonato, J. A., Bray, G. A., Sacks, F. M., & Qi, L. (2021) · International Journal of Obesity · doi:10.1038/s41366-021-00939-7 · Cited by 6
Canyelles, M., Pérez, A., Junza, A., Miñambres, I., Yanes, Ó., Sardà, H., Rotllán, N., Julve, J., Benı́tez, S., Sánchez‐Quesada, J. L., et al. (2022) · Diagnostics · doi:10.3390/diagnostics12112783 · Cited by 6
Yuan, H., Sun, Z., Liu, N., Yang, K., Li, Y., Xu, Q., Guo, Z., & Duan, Y. (2023) · PLoS ONE · doi:10.1371/journal.pone.0293275 · Cited by 6
Dean, Y. E., Rouzan, S. S., Pintado, J. J. L., Talat, N. E., Mohamed, A. R. H., Verma, S., Kamdi, Z. A., Gir, D., Helmy, A., Helmy, Z., et al. (2023) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000001426 · Cited by 7
Wei, M., Liu, J., Wang, X., Liu, X., Jiang, L., Jiang, Y., Ma, Y., Wang, J., Yuan, H., An, X., et al. (2024) · Food & Function · doi:10.1039/d4fo00619d · Cited by 6
Parisis, N. A., Bousdouni, P., Kandyliari, A., Spyridaki, M.-H. E., Koutsogianni, A. D., Telli, C., Tsilidis, K. K., Koutelidakis, A. Ε., & Tzakos, A. G. (2025) · Molecules · doi:10.3390/molecules30112398 · Cited by 6
Chen, P., Ho, C., Shahidi, F., & Pan, M. (2018) · Journal of Food Bioactives · doi:10.31665/jfb.2018.3151 · Cited by 6
Intestinal Dysbiosis and Non-Alcoholic Fatty Liver Disease
Auguet, T., Bertran, L., & Binetti, J. (2021) · Biochemistry · doi:10.5772/intechopen.92972 · Cited by 7
The Metabolomic Rationale for Treating Perimenopausal Syndrome as Kidney Deficiency
Chen, X., Wu, C., Liang, W., Shen, J., Zhuo, Z., Hu, L., Ruan, L., Zhang, P., Xu, L., Li, C., et al. (2020) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2020/8568353 · Cited by 6
Novel Risk Stratification Assays for Acute Coronary Syndrome
Ahmed, H. M., & Hazen, S. L. (2017) · Current Cardiology Reports · doi:10.1007/s11886-017-0880-8 · Cited by 7
Self-citationIs There any Possible Association Between Trimethylamine N-Oxide (TMAO) and Cancer? A Review Study
Khodabakhshi, A., & Rooholamini, M. R. (2021) · Journal of Occupational Health and Epidemiology · doi:10.52547/johe.10.1.17 · Cited by 6
Marsh, K. A., Saunders, A. V., & Zeuschner, C. L. (2016) · IGI Global eBooks · doi:10.4018/978-1-5225-0549-5.ch007 · Cited by 6
Kim, M., Huda, M. N., O’Connor, A., Albright, J., Durbin-Johnson, B. P., & Bennett, B. J. (2021) · Physiological Genomics · doi:10.1152/physiolgenomics.00140.2020 · Cited by 7
Self-citationMonoamine Oxidases and Flavin-Containing Monooxygenases
Cashman, J. R. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64091-6 · Cited by 6
Flavin-containing monooxygenase
Choe, J., Moon, H., & Shin, S. (2018) · Worldwide Protein Data Bank · doi:10.2210/pdb5z8t/pdb · Cited by 6
Battillo, D. J., & Malin, S. K. (2025) · Experimental Physiology · doi:10.1113/ep092550 · Cited by 5
Zhang, H., Ren, K., Ni, X., Lin, L., Li, L., Zhang, W., Gao, Z., Ren, S., Lili, F., & Hai, X. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.118691 · Cited by 5
Lei, Y., Jiang, J., Chen, L., Fang, Q., Li, C., Fei, Y., Qu, S., Xia, Z., Ning, Y., He, M., et al. (2025) · BMC Nephrology · doi:10.1186/s12882-025-04625-y · Cited by 5
Metadata
- Authors
- Bennett, B. J., Vallim, T. Q. D. A., Wang, Z., Shih, D. M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., Edwards, P. A., Hazen, S. L., & Lusis, A. J.
- Affiliations
- University of California, Los Angeles (US)
- Cleveland Clinic (US)
- University of Southern California (US)
- Corresponding author
- Bennett, Brian J.
- Lusis, Aldons J.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 17
- Issue
- 1
- Pages
- 49-60
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3771112
- OpenAlex
- W2046971089
- Cited by
- 1,070
- References
- 35
- Citations by year
- 2026: 75 · 2025: 88 · 2024: 88 · 2023: 95 · 2022: 116 · 2021: 102 · 2020: 107 · 2019: 90 · 2018: 81 · 2017: 50 · 2016: 67 · 2015: 59 · 2014: 32 · 2013: 19
- FWCI
- 64.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Cleveland Clinic
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL3 0568, HL28481, R01HL094322, P01HL030568, R00HL102223, K99HL102223, HL113452, P20HL113452, HL94322, K99/R00 HL102223, R01HL103866, HL103866, P01HL028481)
- National Institute of General Medical Sciences (T32GM088088)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- trimethylamine N-oxide, atherosclerosis, flavin monooxygenase 3, gut microbiota, choline metabolism, bile acids, farnesoid X receptor, androgen regulation, sex differences, genetic variation, dietary regulation
- MeSH terms
- Receptor, Farnesoid X-Activated, Androgens, Animals, Base Sequence, Bile Acids and Salts, Choline, Diet, Female, Humans, Male, Methylamines, Oxygenases, Sex Factors, Down-Regulation, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Polymorphism, Single Nucleotide, Gene Silencing, Atherosclerosis, Mice, HEK293 Cells
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