The DOI matches its Crossref record; 33 of the 35 references it cites were found in a registry or an index.
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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Metabolites Linking the Gut Microbiome with Risk for Type 2 Diabetes
Zhu, T., & Goodarzi, M. O. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00307-3 · Cited by 100
Gut Microbiota and Atherosclerosis—Focusing on the Plaque Stability
Shen, X., Li, L., Sun, Z., Zang, G., Zhang, L., Shao, C., & Wang, Z. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.668532 · Cited by 103
Self-citationLi, Y., Zhang, L., Ren, P., Yang, Y., Li, S., Qin, X., Zhang, M., Zhou, M., & Liu, W. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153812 · Cited by 99
Ryan, P. M., London, L. E. E., Bjorndahl, T. C., Mandal, R., Murphy, K., Fitzgerald, G. F., Shanahan, F., Ross, R. P., Wishart, D. S., Caplice, N. M., et al. (2017) · Microbiome · doi:10.1186/s40168-017-0246-x · Cited by 97
Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases
Constantino-Jonapa, L. A., Espinoza-Palacios, Y., Escalona‐Montaño, A. R., Hernández-Ruiz, P., Amezcua-Guerra, L. M., Amedei, A., & Aguirre‐García, M. M. (2023) · Biomedicines · doi:10.3390/biomedicines11020431 · Cited by 99
Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease
Wilson, A. S., Teft, W. A., Morse, B. L., Choi, Y., Woolsey, S., DeGorter, M. K., Hegele, R. A., Tirona, R. G., & Kim, R. B. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-3797-3 · Cited by 97
Pathogenic functions of host microbiota
Rath, S., Rud, T., Karch, A., Pieper, D. H., & Vital, M. (2018) · Microbiome · doi:10.1186/s40168-018-0542-0 · Cited by 98
A cross-talk between gut microbiome, salt and hypertension
Naqvi, S., Asar, T. O., Kumar, V., Al-Abbasi, F. A., Alhayyani, S., Kamal, M. A., & Anwar, F. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111156 · Cited by 95
Wang, Q., Guo, M., Liu, Y., Xu, M., Shi, L., Li, X., Zhao, J., Zhang, H., Wang, G., & Chen, W. (2022) · Nutrients · doi:10.3390/nu14061222 · Cited by 97
Kawanishi, K., Dhar, C., Do, R., Varki, N., Gordts, P. L. S. M., & Varki, A. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902902116 · Cited by 94
Microbial metabolites in non-alcoholic fatty liver disease
Zhou, D., & Fan, J. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i17.2019 · Cited by 96
Diet-gut microbiota interactions on cardiovascular disease
Zhang, X., & Gérard, P. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.03.028 · Cited by 98
Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy
Li, M., Parker, B. L., Pearson, E., Hunter, B., Cao, J., Koay, Y. C., Guneratne, O., James, D. E., Yang, J. Y. H., Lal, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16584-z · Cited by 95
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Leylabadlo, H. E., Sanaie, S., Heravi, F. S., Ahmadian, Z., & Ghotaslou, R. (2020) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2020.104268 · Cited by 94
The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease
Huang, Y., Xin, W., Xiong, J., Yao, M., Zhang, B., & Zhao, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.837500 · Cited by 93
Zhou, Y., Zhang, Y., Jin, S., Lv, J., Li, M., & Feng, N. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117031 · Cited by 94
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Griffin, J. L., Wang, X., & Stanley, E. G. (2015) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.114.000219 · Cited by 92
Aldana-Hernández, P., Leonard, K.-A., Zhao, Y.-Y., Curtis, J. M., Field, C. J., & Jacobs, R. L. (2020) · The Journal of Nutrition · doi:10.1093/jn/nxz214 · Cited by 91
TMAO as a potential biomarker and therapeutic target for chronic kidney disease: A review
Ye, Z., Lulu, C., Xiangchang, Z., Fang, Q., Binjie, Z., Chunyang, L., Rao, T., & Dongsheng, O. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.929262 · Cited by 91
Liu, J., Zhang, T., Wang, Y., Si, C., Wang, X., Wang, R., & Lv, Z. (2020) · Aging · doi:10.18632/aging.102846 · Cited by 90
Hong, Y., Li, B., Zheng, N., Wu, G., Ma, J., Tao, X., Chen, L., Zhong, J., Sheng, L., & Li, H. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00833 · Cited by 89
The role of the gut microbiome and diet in the pathogenesis of non-alcoholic fatty liver disease
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Probiotics: Current Landscape and Future Horizons
Day, R. L., Harper, A. J., Woods, R. M., Davies, O. G., & Heaney, L. M. (2019) · Future Science OA · doi:10.4155/fsoa-2019-0004 · Cited by 92
Kaliannan, K., Li, X., Wang, B., Pan, Q., Chen, C., Hao, L., Xie, S., & Kang, J. X. (2019) · Communications Biology · doi:10.1038/s42003-019-0521-4 · Cited by 88
Pathak, P., Helsley, R. N., Brown, A. L., Buffa, J. A., Choucair, I., Nemet, I., Baleanu‐Gogonea, C., Gogonea, V., Wang, Z., Garcı́a-Garcı́a, J. C., et al. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00584.2019 · Cited by 89
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Oktaviono, Y. H., Lamara, A. D., Saputra, P. B. T., Arnindita, J. N., Pasahari, D., Saputra, M. E., & Suasti, N. M. A. (2023) · Biomolecules and Biomedicine · doi:10.17305/bb.2023.8893 · Cited by 92
Sexual dimorphism of cardiometabolic dysfunction: Gut microbiome in the play?
Cross, T.-W. L., Kasahara, K., & Rey, F. E. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.05.016 · Cited by 87
Andrikopoulos, P., Aron‐Wisnewsky, J., Chakaroun, R., Myridakis, A., Forslund, S. K., Nielsen, T., Adriouch, S., Holmes, B., Chilloux, J., Vieira‐Silva, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39824-4 · Cited by 88
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Shore, S. A., & Cho, Y. (2016) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0052ps · Cited by 86
Org, E., Mehrabian, M., & Lusis, A. J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.05.035 · Cited by 85
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Panyod, S., Wu, W., Chen, P.-C., Chong, K.-V., Yang, Y.-T., Chuang, H.-L., Chen, C., Chen, R.-A., Liu, P., Chung, C., et al. (2022) · npj Biofilms and Microbiomes · doi:10.1038/s41522-022-00266-3 · Cited by 85
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Seldin, M. M., Koplev, S., Rajbhandari, P., Vergnes, L., Rosenberg, G. M., Meng, Y., Pan, C., Phuong, T. M. N., Gharakhanian, R., Che, N., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.015 · Cited by 84
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Bluemel, S., Williams, B., Knight, R. D., & Schnabl, B. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00245.2016 · Cited by 85
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Teft, W. A., Morse, B. L., Leake, B. F., Wilson, A. S., Mansell, S. E., Hegele, R. A., Ho, R. H., & Kim, R. B. (2016) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.6b00937 · Cited by 83
Evolving targets for the treatment of atherosclerosis
Solanki, A., Bhatt, L. K., & Johnston, T. P. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.02.002 · Cited by 83
Xu, M., Lv, C., Wang, H., Lu, Q., Ye, M., Zhu, X., & Liu, R. (2022) · Food Research International · doi:10.1016/j.foodres.2022.111014 · Cited by 83
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Manta, B., & Gladyshev, V. N. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.02.010 · Cited by 84
Tripolt, N. J., Leber, B., Triebl, A., Köfeler, H. C., Stadlbauer, V., & Sourij, H. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.05.005 · Cited by 83
Flavin-containing monooxygenases in aging and disease: Emerging roles for ancient enzymes
Rossner, R., Kaeberlein, M. R., & Leiser, S. F. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.779678 · Cited by 81
Heianza, Y., Sun, D., Smith, S. R., Bray, G. A., Sacks, F. M., & Qi, L. (2018) · Diabetes Care · doi:10.2337/dc17-2108 · Cited by 81
Metaorganismal nutrient metabolism as a basis of cardiovascular disease
Brown, J. M., & Hazen, S. L. (2014) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000036 · Cited by 80
Self-citationRamezani, A., Nolin, T. D., Barrows, I. R., Serrano, M. G., Buck, G. A., Regunathan-Shenk, R., West, R. E., Latham, P. S., AMDUR, R. L., & Raj, D. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-33018-5 · Cited by 82
Yang, Y., Wang, Y., Sun, J., Zhang, J., Guo, H., Shi, Y., Cheng, X., Tang, X., & Le, G. (2018) · Food & Function · doi:10.1039/c8fo01629a · Cited by 78
Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults
Erickson, M. L., Malin, S. K., Wang, Z., Brown, J. M., Hazen, S. L., & Kirwan, J. P. (2019) · Nutrients · doi:10.3390/nu11010179 · Cited by 83
Self-citationThe gut microbiome as novel cardio-metabolic target: the time has come!
Vinje, S., Stroes, E. S. G., Nieuwdorp, M., & Hazen, S. L. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht467 · Cited by 80
Self-citationGut-microbiota derived bioactive metabolites and their functions in host physiology
Debnath, N., Kumar, R., Kumar, A., Mehta, P. K., & Yadav, A. K. (2021) · Biotechnology and Genetic Engineering Reviews · doi:10.1080/02648725.2021.1989847 · Cited by 77
Nanto-Hara, F., Kanemitsu, Y., Fukuda, S., Kikuchi, K., Asaji, K., Saigusa, D., Iwasaki, T., Ho, H., Mishima, E., Suzuki, T., et al. (2019) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfz126 · Cited by 76
Gao, J., Yan, K.-T., Wang, J.-X., Dou, J., Wang, J., Ren, M., Ma, J., Zhang, X., & Liu, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-59235-5 · Cited by 76
Li, Z. H. (2024) · Gut · doi:10.1136/gutjnl-2024-331880 · Cited by 79
Egg consumption and heart health: A review
Clayton, Z. S., Fusco, E., & Kern, M. (2016) · Nutrition · doi:10.1016/j.nut.2016.12.014 · Cited by 75
Trimethylamine N -oxide: heart of the microbiota–CVD nexus?
Naghipour, S., Cox, A. J., Peart, J. N., Toit, E. F. D., & Headrick, J. P. (2020) · Nutrition Research Reviews · doi:10.1017/s0954422420000177 · Cited by 77
Amelioration of TMAO through probiotics and its potential role in atherosclerosis
Din, A. U., Hassan, A., Zhu, Y. S., Yin, T., Gregersen, H. N., & Wang, G. (2019) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-019-10142-4 · Cited by 76
Awwad, H. M., Geisel, J., & Obeid, R. (2016) · Journal of Chromatography B · doi:10.1016/j.jchromb.2016.10.017 · Cited by 73
Annunziata, G., Maisto, M., Schisano, C., Ciampaglia, R., Narciso, V., Hassan, S. T. S., Tenore, G. C., & Novellino, E. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00575 · Cited by 72
Association of TrimethylamineN-Oxide and Related Metabolites in Plasma and Incident Type 2 Diabetes
Lemaître, R. N., Jensen, P. N., Wang, Z., Fretts, A. M., McKnight, B., Nemet, I., Biggs, M. L., Sotoodehnia, N., Otto, M. C. D. O., Psaty, B. M., et al. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.22844 · Cited by 71
Self-citationTrimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis
Wilson, A., McLean, C., & Kim, R. B. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000274 · Cited by 71
Phillips, I. R., & Shephard, E. A. (2019) · Xenobiotica · doi:10.1080/00498254.2019.1643515 · Cited by 72
Hernandez, L. N., Ward, L. J., Arefin, S., Ebert, T., Laučytė-Cibulskienė, A., Collaborators, G.-F., Pilote, L., Norris, C. M., Raparelli, V., Kautzky‐Willer, A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-08387-7 · Cited by 70
Modulation of Endothelial Function by TMAO, a Gut Microbiota-Derived Metabolite
Querio, G., Antoniotti, S., Geddo, F., Levi, R. C., & Gallo, M. P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065806 · Cited by 70
Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality
Molinaro, A., Nemet, I., Lassen, P. B., Chakaroun, R., Nielsen, T., Aron‐Wisnewsky, J., Bergh, P., Li, L., Henricsson, M., Køber, L., et al. (2023) · JACC Heart Failure · doi:10.1016/j.jchf.2023.03.008 · Cited by 73
Self-citationTemel, R. E., & Brown, J. M. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.04.002 · Cited by 75
Navab, M., Hough, G., Buga, G. M., Su, F., Wagner, A. C., Meriwether, D., Chattopadhyay, A., Gao, F., Grijalva, V. R., Danciger, J. S., et al. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m042051 · Cited by 69
Self-citationChen, P., Li, S., Koh, Y., Wu, J.-C., Yang, M., Ho, C., & Pan, M. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b03092 · Cited by 69
Gut microbiota in dementia. Critical review of novel findings and their potential application
Łuc, M., Misiak, B., Pawłowski, M., Stańczykiewicz, B., Zabłocka, A., Szcześniak, D. M., Pałęga, A., & Rymaszewska, J. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110039 · Cited by 69
Srinivasa, S., Fitch, K. V., Lo, J., Kadar, H., Knight, R., Wong, K., Abbara, S., Gauguier, D., Capeau, J., Boccara, F., et al. (2015) · AIDS · doi:10.1097/qad.0000000000000565 · Cited by 68
Chan, M. M.-Y., Yang, X., Wang, H., Saaoud, F., Sun, Y., & Fong, D. (2019) · Nutrients · doi:10.3390/nu11081821 · Cited by 68
Hu, Y., Zhao, Y., Yuan, L., & Yang, X. (2015) · Food & Function · doi:10.1039/c5fo00581g · Cited by 68
Petriello, M. C., Brandon, J. A., Hoffman, J., Wang, C., Tripathi, H., Abdel-Latif, A., Ye, X., Li, X., Yang, L., Lee, E., et al. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfx275 · Cited by 67
Shih, D. M., Zhu, W., Schugar, R. C., Meng, Y., Jia, X., Miikeda, A., Wang, Z., Zieger, M., Lee, R., Graham, M., et al. (2019) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.119.312592 · Cited by 67
Self-citationGut microbiota: a non-target victim of pesticide-induced toxicity
Sharma, T., Natesh, N. S., Pothuraju, R., Batra, S. K., & Rachagani, S. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2187578 · Cited by 68
Responsiveness of cardiometabolic-related microbiota to diet is influenced by host genetics
O’Connor, A., Quizon, P. M., Albright, J., Lin, F. T., & Bennett, B. J. (2014) · Mammalian Genome · doi:10.1007/s00335-014-9540-0 · Cited by 68
Self-citationBile acids at the cross-roads of gut microbiome–host cardiometabolic interactions
Ryan, P. M., Stanton, C., & Caplice, N. M. (2017) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-017-0299-9 · Cited by 70
The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis
O’Morain, V. L., & Ramji, D. P. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900797 · Cited by 66
Shang, R., Sun, Z., & Li, H. (2014) · BMC Cardiovascular Disorders · doi:10.1186/1471-2261-14-88 · Cited by 66
Ren, D., Liu, Y., Zhao, Y., & Yang, X. (2016) · Food and Chemical Toxicology · doi:10.1016/j.fct.2016.06.004 · Cited by 66
Long-term effects of western diet consumption in male and female mice
Hasegawa, Y., Chen, S., Sheng, L., Jena, P. K., Kalanetra, K. M., Mills, D. A., Wan, Y. Y., & Slupsky, C. M. (2020) · Scientific Reports · doi:10.1038/s41598-020-71592-9 · Cited by 65
Emerging roles of flavin monooxygenase 3 in cholesterol metabolism and atherosclerosis
Schugar, R. C., & Brown, J. M. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000215 · Cited by 67
Șerban, M.-C., Sahebkar, A., Mikhailidis, D. P., Toth, P. P., Jones, S. R., Muntner, P., Blaha, M. J., Andrica, F., Martin, S. S., Borza, C., et al. (2016) · Scientific Reports · doi:10.1038/srep19188 · Cited by 65
Self-citationDietary reference values for chloride
EFSA Panel on Nutrition, N. F. A. F. A. (., Turck, D., Castenmiller, J. J. M., Henauw, S. D., Hirsch‐Ernst, K. I., Kearney, J., Knutsen, H. K., Maciuk, A., Mangelsdorf, I., McArdle, H. J., et al. (2019) · EFSA Journal · doi:10.2903/j.efsa.2019.5779 · Cited by 68
IRF1-mediated downregulation of PGC1α contributes to cardiorenal syndrome type 4
Huang, Y., Wang, S., Zhou, J., Liu, Y., Du, C., Yang, K., Bi, X., Liu, M., Han, W., Wang, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18519-0 · Cited by 65
FMO3 and its metabolite TMAO contribute to the formation of gallstones
Chen, Y., Weng, Z., Liu, Q., Shao, W., Guo, W., Chen, C., Jiao, L. R., Wang, Q., Lu, Q., Sun, H., et al. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.06.016 · Cited by 64
Ashammakhi, N. A., Darabi, M. A., Çelebi‐Saltik, B., Tutar, R., Hartel, M. C., Lee, J., Hussein, S. M., Goudie, M. J., Cornelius, M. B., Dokmeci, M. R., et al. (2019) · Small Methods · doi:10.1002/smtd.201900589 · Cited by 67
Treatment of Dyslipidemia through Targeted Therapy of Gut Microbiota
Flaig, B., Garza, R., Singh, B., Hamamah, S., & Covașă, M. (2023) · Nutrients · doi:10.3390/nu15010228 · Cited by 65
Trimethylamine emissions in animal husbandry
Sintermann, J., Schallhart, S., Kajos, M. K., Jocher, M., Bracher, A., Münger, A., Johnson, D., Neftel, A., & Ruuskanen, T. M. (2014) · Biogeosciences · doi:10.5194/bg-11-5073-2014 · Cited by 64
Circulating trimethylamine N-oxide levels following fish or seafood consumption
Wang, Z., Tang, W. H. W., O’Connell, T. F., Garcia, E., Jeyarajah, E. J., Li, X. S., Jia, X., Weeks, T. L., & Hazen, S. L. (2022) · European Journal of Nutrition · doi:10.1007/s00394-022-02803-4 · Cited by 63
Self-citationZhao, X., Zeisel, S. H., & Zhang, S. (2015) · Electrophoresis · doi:10.1002/elps.201500055 · Cited by 64
Papandreou, C., Bulló, M., Zheng, Y., Ruiz‐Canela, M., Yu, E., Guasch‐Ferré, M., Toledo, E., Clish, C. B., Corella, D., Estruch, R., et al. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy058 · Cited by 65
Gut Microbiota-Derived Mediators as Potential Markers in Nonalcoholic Fatty Liver Disease
Aragonès, G., González-García, S., Aguilar, C., Richart, C., & Auguet, T. (2019) · BioMed Research International · doi:10.1155/2019/8507583 · Cited by 69
Orman, M., Bodea, S., Funk, M. A., Campo, A. M.-D., Bollenbach, M., Drennan, C. L., & Balskus, E. P. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b04883 · Cited by 64
Liang, X., Zhang, Z., Lv, Y., Tong, L., Liu, T., Yi, H., Zhou, X., Yu, Z., Tian, X., Cui, Q., et al. (2020) · Nutrition · doi:10.1016/j.nut.2020.110941 · Cited by 62
Li, S., Chen, S. X., Lu, X., Fang, A., Chen, Y., Huang, R.-Z., Lin, X., Huang, Z.-H., Ma, J.-F., Huang, B., et al. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03581-7 · Cited by 63
Tacconi, E., Palma, G., Biase, D. D., Luciano, A., Barbieri, M., de Nigris, F., & Bruzzese, F. (2023) · Nutrients · doi:10.3390/nu15030563 · Cited by 62
Garcia, E., Wolak, J. E., Wang, Z., Li, X. S., Bennett, D. W., Connelly, M. A., Otvos, J. D., Hazen, S. L., & Jeyarajah, E. J. (2017) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2017.06.003 · Cited by 62
Self-citation
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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