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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The 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 [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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Flagged first, then by citations
2 of the 35 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 501–600 of 1,000
Obesity, Asthma, and the Microbiome
Cho, Y., & Shore, S. A. (2016) · Physiology · doi:10.1152/physiol.00045.2015 · Cited by 31
Impact of nutrition on pollutant toxicity: an update with new insights into epigenetic regulation
Hoffman, J. B., Petriello, M. C., & Hennig, B. (2017) · Reviews on Environmental Health · doi:10.1515/reveh-2016-0041 · Cited by 30
Fadhlaoui, K., Arnal, M.-É., Martineau, M., Camponova, P., Ollivier, B., O’Toole, P. W., & Brugère, J. (2020) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-020-10599-8 · Cited by 33
Evidence of adequacy of postpartum care for immigrant women.
Katz, D., & Gagnon, A. J. (2002) · PubMed · Cited by 30
Papa, A., Santini, P., Lucia, S. S. D., Maresca, R., Porfidia, A., Pignatelli, P., Gasbarrini, A., Violi, F., & Pola, R. (2023) · Thrombosis Research · doi:10.1016/j.thromres.2023.11.005 · Cited by 29
Jiang, C., Wang, S., Wang, Y., Wang, K., Huang, C., Gao, F., Hu, H., Deng, Y., Zhang, W., Zheng, J., et al. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155349 · Cited by 29
Bollenbach, M., Ortega, M. A., Orman, M., Drennan, C. L., & Balskus, E. P. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00005 · Cited by 29
Trimethylamine-N-oxide acutely increases cardiac muscle contractility
Oakley, C. I., Vallejo, J. A., Wang, D. D., Gray, M., Tiede-Lewis, L. M., Shawgo, T., Daon, E., Zorn, G. L., Stubbs, J. R., & Wacker, M. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00507.2019 · Cited by 30
Understanding connections and roles of gut microbiome in cardiovascular diseases
Rajendiran, E., Ramadass, B., & Ramprasath, V. R. (2020) · Canadian Journal of Microbiology · doi:10.1139/cjm-2020-0043 · Cited by 29
Krishnan, S., O’Connor, L. E., Wang, Y., Gertz, E., Campbell, W. W., & Bennett, B. J. (2021) · British Journal Of Nutrition · doi:10.1017/s0007114521004694 · Cited by 30
Self-citationNew Insight into the Dietary Cause of Atherosclerosis: Implications for Pharmacology
Spector, R. (2016) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.233296 · Cited by 29
Plasma trimethylamine‐N‐oxide following supplementation with vitamin D or D plus B vitamins
Obeid, R., Awwad, H. M., Kirsch, S. H., Waldura, C., Herrmann, W., Graeber, S. M., & Geisel, J. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600358 · Cited by 29
Functional food addressing heart health: do we have to target the gut microbiota?
Ryan, P. M., Ross, R. P., Fitzgerald, G. F., Caplice, N. M., & Stanton, C. (2015) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0000000000000224 · Cited by 28
Elam, R. E., Bůžková, P., Barzilay, J. I., Wang, Z., Nemet, I., Budoff, M. J., Cauley, J. A., Fink, H. A., Lee, Y., Robbins, J. A., et al. (2022) · Bone · doi:10.1016/j.bone.2022.116431 · Cited by 28
Self-citationLemaître, R. N., Jensen, P. N., Wang, Z., Fretts, A. M., Sitlani, C. M., Nemet, I., Sotoodehnia, N., Otto, M. C. D. O., Zhu, W., Budoff, M. J., et al. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.122.029230 · Cited by 29
Self-citationFarnesoid X receptor: From Structure to Function and Its Pharmacology in Liver Fibrosis
Ding, C., Wang, Z., Dou, X., Yang, Q., Ning, Y., Kao, S., Sang, X., Hao, M., Wang, K., Peng, M., et al. (2023) · Aging and Disease · doi:10.14336/ad.2023.0830 · Cited by 29
Self-citationMi, S., Zhao, Y., Jacobs, R. L., & Curtis, J. M. (2016) · Journal of Separation Science · doi:10.1002/jssc.201600926 · Cited by 28
Liu, J., Lai, L., Lin, J., Zheng, J., Nie, X., Zhu, X., Xue, J., & Liu, T. (2020) · International Journal of Biological Sciences · doi:10.7150/ijbs.40934 · Cited by 28
Ding, Q., Tian, J., Li, M., Lian, F., Zhao, L., Wei, X., Han, L., Zheng, Y., Gao, Z., Yang, H., et al. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.530160 · Cited by 28
Yu, P.-S., Wu, P., Hung, W., Lin, M., Zhen, Y., Hung, W., Chang, J., Tsai, J., Chiu, Y., Hwang, S., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae009 · Cited by 28
Andraos, S., Lange, K., Clifford, S. A., Jones, B., Thorstensen, E. B., Kerr, J. A., Wake, M. A., Saffery, R., Burgner, D. P., & O'Sullivan, J. M. (2020) · Current Developments in Nutrition · doi:10.1093/cdn/nzaa103 · Cited by 29
Schugar, R. C., Willard, B. B., Wang, Z., & Brown, J. M. (2017) · Adipocyte · doi:10.1080/21623945.2017.1398295 · Cited by 31
Self-citationChakraborty, P., Banerjee, D., Majumder, P., & Sarkar, J. (2024) · Medicine in Microecology · doi:10.1016/j.medmic.2024.100104 · Cited by 28
Polysaccharides to postbiotics: Nurturing bone health via modulating “gut-immune axis”
Yadav, S., Sapra, L., & Srivastava, R. K. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.134655 · Cited by 29
Trisal, A., Singh, I., Garg, G., Jorwal, K., & Singh, A. K. (2024) · 3 Biotech · doi:10.1007/s13205-024-04187-0 · Cited by 27
Yu, Q., Zhu, J., Huang, M., Bai, J., Zhu, Y., Zhao, Y., Yang, Y., & Xiao, X. (2025) · Food Research International · doi:10.1016/j.foodres.2025.117394 · Cited by 28
Intestinal microbiota in primary sclerosing cholangitis
Hov, J. R., & Kummen, M. (2016) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000334 · Cited by 29
Ebert, T., Painer, J., Bergman, P., Qureshi, A. R., Giroud, S., Stalder, G. L., Kublickiene, K. R., Göritz, F., Vetter, S. G., Bieber, C., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-76346-1 · Cited by 27
Ramireddy, L., Tsen, H., Chiang, Y.-C., Hung, C.-Y., Wu, S.-R., Young, S.-L., Lin, J., Huang, C., Chiu, S., Chen, C., et al. (2021) · Foods · doi:10.3390/foods10122931 · Cited by 28
Quantification of choline in serum and plasma using a clinical nuclear magnetic resonance analyzer
Garcia, E., SHALAUROVA, I. Y., Matyus, S. P., Wolak, J. E., Oskardmay, D. N., & Connelly, M. A. (2021) · Clinica Chimica Acta · doi:10.1016/j.cca.2021.11.031 · Cited by 27
Xiang, Z., Wu, J., Li, J., Zheng, S., Wei, X., & Xu, X. (2023) · Engineering · doi:10.1016/j.eng.2022.12.012 · Cited by 27
wild-type choline TMA lyase in complex with betaine aldehyde
Funk, M. A., & Drennan, C. L. (2018) · Worldwide Protein Data Bank · doi:10.2210/pdb6nd3/pdb · Cited by 27
Mao, L., Gao, B., Chang, H., & Shen, H. (2024) · Metabolites · doi:10.3390/metabo14010043 · Cited by 27
Miao, T., Zhang, X., Zhang, C., Wu, J., Zhu, Y., Xiao, M., Zhang, N., Zhong, Y., Liu, Y., Lin, Y., et al. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107232 · Cited by 26
Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke
Li, Z., He, X., Fang, Q., & Yin, X. (2024) · Biomolecules · doi:10.3390/biom14111463 · Cited by 26
Heinrich‐Sanchez, Y., & Vital, M. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2525403 · Cited by 27
TMAO and Cardiovascular Disease: Exploring Its Potential as a Biomarker
Amariței, O., Mierlan, O. L., Dinu, C. A., Chiscop, I., Matei, M. N., Guțu, C., & Gurău, G. (2025) · Medicina · doi:10.3390/medicina61101767 · Cited by 28
Restini, C. B. A., Fink, G. D., & Watts, S. W. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105273 · Cited by 27
Heng, X., Liu, W., & Chu, W. (2020) · Microbial Pathogenesis · doi:10.1016/j.micpath.2020.104658 · Cited by 26
Senesi, P., Ferrulli, A., Luzi, L., & Terruzzi, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22157772 · Cited by 26
Targets of statins intervention in LDL-C metabolism: Gut microbiota
Sun, C., Wang, Z., Hu, L., Zhang, X., Chen, J., Yu, Z., Liu, L., & Wu, M. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.972603 · Cited by 26
Self-citationJing, J., Guo, J., Dai, R., Zhu, C., & Zhang, Z. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1252907 · Cited by 28
Jiang, Y., Jin, J., Iakova, P. A., Hernandez, J. C., Jawanmardi, N., Sullivan, E. M., Guo, G. L., Timchenko, N. A., & Darlington, G. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.08.003 · Cited by 27
Cardona, A., O’Brien, A., Bernier, M. C., Somogyi, Á., Wysocki, V. H., Smart, S., He, X., Ambrosio, G., Hsueh, W. A., & Raman, S. V. (2019) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2019-000718 · Cited by 26
Human Gut Microbiota in Cardiovascular Disease
Ronen, D., Rokach, Y., Abedat, S., Qadan, A., Daana, S., Amir, O., & Asleh, R. (2024) · Comprehensive physiology · doi:10.1002/cphy.c230012 · Cited by 28
Chittimalli, K., Jahan, J., Sakamuri, A., McAdams, Z. L., Ericsson, A. C., & Jarajapu, Y. P. R. (2023) · Clinical Science · doi:10.1042/cs20220904 · Cited by 25
Xu, X., Zhang, F., Ren, J., Zhang, H., Jing, C., Wei, M., Jiang, Y., & Xie, H. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1243095 · Cited by 25
Zhang, L., Ko, C., & Zeng, Y.-M. (2022) · Nature and Science of Sleep · doi:10.2147/nss.s354742 · Cited by 26
Intrapersonal Stability of Plasma Metabolomic Profiles over 10 Years among Women
Zeleznik, O. A., Wittenbecher, C., Deik, A., Jeanfavre, S., Ávila-Pacheco, J., ROSNER, B. A., Rexrode, K. M., Clish, C. B., Hu, F. B., & Eliassen, A. H. (2022) · Metabolites · doi:10.3390/metabo12050372 · Cited by 25
A Bibliometric Analysis of Research on the Links Between Gut Microbiota and Atherosclerosis
Wang, Y., Li, D., Jia, Z., Hui, J., Xin, Q., Zhou, Q., Cong, W., & Xu, F. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.941607 · Cited by 25
Gautam, A., Paudel, Y., Abidin, S., & Bhandari, U. (2018) · Human & Experimental Toxicology · doi:10.1177/0960327118817862 · Cited by 25
Baranyi, A., Enko, D., von Lewinski, D., Rothenhäusler, H., Amouzadeh-Ghadikolai, O., Harpf, H. H., Harpf, L., Traninger, H., Obermayer-Pietsch, B. M., Schweinzer, M., et al. (2021) · European Journal of Psychotraumatology · doi:10.1080/20008198.2021.1920201 · Cited by 24
Jomard, A., Liberale, L., Doytcheva, P., Reiner, M. F., Müller, D., Visentin, M., Bueter, M., Lüscher, T. F., Vettor, R., Lutz, T. A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-12720-5 · Cited by 26
Ge, P., Tai, T., Jiang, L., Ji, J., Mi, Q., Zhu, T., Li, Y., & Xie, H. (2023) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2022.10.010 · Cited by 24
Ghaffari, M. H., Daniel, J., Sadri, H., Schuchardt, S., Martín‐Tereso, J., & Sauerwein, H. (2023) · Journal of Dairy Science · doi:10.3168/jds.2023-23841 · Cited by 24
Lower plasma choline levels are associated with sleepiness symptoms
Pak, V. M., Dai, F., Keenan, B. T., Gooneratne, N. S., & Pack, A. I. (2017) · Sleep Medicine · doi:10.1016/j.sleep.2017.10.004 · Cited by 25
Wu, X., Li, C., Mariyam, Z., Jiang, P., Zhou, M., Zeb, F., Haq, I. U., Chen, A., & Feng, Q. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26600 · Cited by 24
Ellenbogen, J., Jiang, R., Kountz, D. J., Zhang, L., & Krzycki, J. A. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101327 · Cited by 24
Metabonomic profiling of chronic intermittent hypoxia in a mouse model
Conotte, S., Tassin, A., Conotte, R., Colet, J., Boudjeltia, K. Z., & Legrand, A. (2018) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2018.02.015 · Cited by 24
Oxygen-Dependent Cell-to-Cell Variability in the Output of the Escherichia coli Tor Phosphorelay
Roggiani, M., & Goulian, M. (2015) · Journal of Bacteriology · doi:10.1128/jb.00074-15 · Cited by 24
Wang, J., Long, C., Zhang, H., Zhang, Y., Wang, H., Yue, H., Wang, X., Wu, S., & Qi, G. (2016) · International Journal of Biological Sciences · doi:10.7150/ijbs.16472 · Cited by 23
Trimethylamine N-oxide (TMAO): a new attractive target to decrease cardiovascular risk
Swanepoel, I., Roberts, A. M., Brauns, C., Chaliha, D. R., Papa, V., Palmer, R. D., & Vaccarezza, M. (2021) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2021-139839 · Cited by 23
Hong, B. V., Agus, J., Tang, X., Zheng, J. J., Romo, E. Z., Lei, S., & Zivkovic, A. M. (2023) · Current Atherosclerosis Reports · doi:10.1007/s11883-023-01148-5 · Cited by 23
Yazdekhasti, N., Brandsch, C., Schmidt, N., Schloesser, A., Huebbe, P., Rimbach, G. H., & Stangl, G. I. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500537 · Cited by 23
Host–Microbiota Mutualism in Metabolic Diseases
Fabbiano, S., Suárez-Zamorano, N., & Trajkovski, M. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00267 · Cited by 23
Guo, F., Zhou, J., Li, Z., Yu, Z., & Ouyang, D. (2020) · Cardiology Research and Practice · doi:10.1155/2020/5854919 · Cited by 23
Ganapathy, T. P., Yuan, J.-T., Ho, M. Y.-M., Wu, K. K.-L., Hoque, M. M., Wang, B., Li, X., Wang, K., Wabitsch, M., Feng, X., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63905-1 · Cited by 22
Implications of gut microbiome on coronary artery disease
Xu, J., & Yang, Y. (2020) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt-20-428 · Cited by 22
Novel Mechanisms and Therapeutic Targets for Ischemic Stroke: A Focus on Gut Microbiota
Bao, Z., Zhang, Z., Zhou, G., Zhang, A., Shao, A., & Zhou, F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.871720 · Cited by 22
Xu, N., Wan, J., Wang, C., Liu, J., Qian, C., & Tan, H. (2022) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s370206 · Cited by 22
New Biomarkers to Evaluate Hyperandrogenemic Women and Hypogonadal Men
Karakas, S. E., & Surampudi, P. N. (2018) · Advances in clinical chemistry · doi:10.1016/bs.acc.2018.06.001 · Cited by 23
Narasimhulu, C. A., Burge, K. Y., Doomra, M., Riad, A., & Parthasarathy, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-29849-x · Cited by 22
Gut microbiota signatures and lipids metabolism profiles by exposure to polyene phosphatidylcholine
Yu, H., Yu, Z. J., Huang, H., Li, P., Tang, Q., Wang, X., & Shen, S. (2019) · BioFactors · doi:10.1002/biof.1495 · Cited by 22
Diet, Microbes, and Murine Atherosclerosis
Getz, G. S., & Reardon, C. A. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.311513 · Cited by 22
Gut microbiota-derived metabolites and chronic inflammatory diseases
Vargas, A., Robinson, B. L., Houston, K., Sangay, A. R. V., Saadeh, M., D’Souza, S. M., & Johnson, D. A. (2025) · Exploration of Medicine · doi:10.37349/emed.2025.1001275 · Cited by 24
Microvascular endothelial dysfunction in vascular senescence and disease
Kasal, D. A. B., Sena, V., Huguenin, G. V. B., Lorenzo, A. D., & Tibiriçá, E. V. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1505516 · Cited by 22
Song, J., Huang, M., Shi, X., Li, X., Chen, X., He, Z., Li, J., Xu, G., & Zheng, J. (2021) · Animals · doi:10.3390/ani12010048 · Cited by 21
Thomas, M. S., DiBella, M., Blesso, C. N., Malysheva, O., Caudill, M. A., Sholola, M. J., Cooperstone, J. L., & Fernández, M. L. (2022) · Nutrients · doi:10.3390/nu14061179 · Cited by 22
Massey, W. J., Osborn, L. J., Banerjee, R., Horak, A. J., Fung, K. K., Orabi, D., Chan, E. R., Sangwan, N., Wang, Z., & Brown, J. M. (2022) · Metabolites · doi:10.3390/metabo12040364 · Cited by 21
Self-citationThe gut microbiome and obstructive sleep apnea syndrome in children
Liu, W., Du, Q., Zhang, H., & Han, D. (2022) · Sleep Medicine · doi:10.1016/j.sleep.2022.09.022 · Cited by 21
Luo, K., Peters, B. A., Moon, J., Xue, X., Wang, Z., Usyk, M., Hanna, D. B., LANDAY, A. L., Schneider, M. F., Gustafson, D., et al. (2024) · Genome Medicine · doi:10.1186/s13073-024-01336-1 · Cited by 21
Self-citationFrano, M. R. L., Fahrmann, J. F., Grapov, D., Fiehn, O., Pedersen, T. L., Newman, J. W. I., Underwood, M. A., Steinhorn, R. H., & Wedgwood, S. (2017) · Metabolomics · doi:10.1007/s11306-017-1170-6 · Cited by 21
Coronary heart disease and intestinal microbiota
Liu, L., He, X., & Feng, Y. (2019) · Coronary Artery Disease · doi:10.1097/mca.0000000000000758 · Cited by 22
Liu, W., Chen, P.-H., & Chen, L.-W. (2020) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2020.108384 · Cited by 21
Wang, M., Li, L., Chen, Y., Lian, G., Wang, J., Zhang, J., Shan, K., Shang, L., Tian, F., & Jing, C. (2020) · Obesity Surgery · doi:10.1007/s11695-020-04974-7 · Cited by 22
Trimethylamine N‐Oxide Electrochemical Biosensor with a Chimeric Enzyme
Mitrova, B., Waffo, A. F. T., Kaufmann, P., Iobbi‐Nivol, C., Leimkühler, S., & Wollenberger, U. (2018) · ChemElectroChem · doi:10.1002/celc.201801422 · Cited by 21
Pan, S., Zhao, D., Duan, S., & Chen, X. (2023) · International Urology and Nephrology · doi:10.1007/s11255-023-03500-9 · Cited by 22
Xie, L., Zhao, B.-X., Luo, J., Li, Y., Zhu, F., Li, G.-F., He, M., Wang, B., Zhang, H., Cai, Y., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2019.11.011 · Cited by 20
Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers
Chen, Y., Xu, J., Pan, Y., Yan, H., Jing, J., Yang, Y., Wang, X., Wan, H., Gao, Y., Han, S., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.648702 · Cited by 20
Verma, D., Sajwan, R. K., Lakshmi, G. B. V. S., Kumar, A., & Solanki, P. R. (2022) · Environmental Science Nano · doi:10.1039/d2en00624c · Cited by 20
Gan, G., Zhang, R., Lu, B., Luo, Y., Chen, S., Lei, H., Li, Y., Cai, Z., & Huang, X. (2022) · International Endodontic Journal · doi:10.1111/iej.13845 · Cited by 20
Wu, B., Liu, Y., Li, H., Zhu, L., Zeng, L., Zhang, Z., & Peng, W. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.391305 · Cited by 22
Taesuwan, S., Vermeylen, F., Caudill, M. A., & Cassano, P. A. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy330 · Cited by 20
The human gut microbiome – a new and exciting avenue in cardiovascular drug discovery
Du, Y., Li, X., Su, C., Wang, L., Jiang, J., & Hong, B. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1638909 · Cited by 20
Parasites, microbiota and metabolic disease
Bhattacharjee, S., Kalbfuß, N., & da Costa, C. P. (2016) · Parasite Immunology · doi:10.1111/pim.12390 · Cited by 20
Liu, J., Ge, P., Luo, Y., Sun, Z., Luo, X., Li, H., Pei, B., Xun, L., Zhang, X., Jiang, Y., et al. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s512207 · Cited by 20
Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis
Koçyiğit, D., Tokgözoğlu, L. S., Gürses, K. M., Ståhlman, M., Borén, J., Soyal, T., Canpınar, H., Güç, D., Sağlam, A., Hazırolan, T., et al. (2020) · Acta cardiologica. Supplementum · doi:10.1080/00015385.2020.1853968 · Cited by 19
Xue, J., Xu, J., Zhao, M., Jin, A., Cheng, A., Jiang, X., Li, K., Lin, J., Meng, X., Li, H., et al. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.122.027265 · Cited by 19
Avilés‐Jiménez, F. (2022) · BioMed Research International · doi:10.1155/2022/9943158 · Cited by 19
Gut Microbiota and Cardiovascular System: An Intricate Balance of Health and the Diseased State
Bhat, M. A., Mishra, A. K., Tantray, J. A., Alatawi, H. A., Saeed, M., Rahman, S., & Jan, A. T. (2022) · Life · doi:10.3390/life12121986 · Cited by 21
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
