{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:24:59Z","timestamp":1787574299029,"version":"build-2736575974"},"reference-count":73,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Trimethylamine N-oxide (TMAO) and homocysteine are key biomarkers linked to cardiovascular and chronic kidney disease (CKD). Although they originate from distinct metabolic pathways, their circulating levels are jointly shaped by renal clearance, systemic metabolic status, and nutrient availability, complicating their biological interpretation. TMAO derives from gut microbiota\u2013dependent metabolism of dietary precursors followed by hepatic oxidation of trimethylamine, whereas homocysteine is a central intermediate of one-carbon metabolism governed by remethylation and transsulfuration. Choline and betaine provide a nutritional interface between these pathways because choline can contribute to microbial TMA production and betaine acts as a methyl donor for homocysteine remethylation via betaine\u2013homocysteine methyltransferase (BHMT). However, this interface does not establish direct metabolic interdependence between circulating TMAO and homocysteine. Declining renal function promotes the accumulation of both TMAO and homocysteine, although their renal handling and the mechanisms underlying their increase in CKD are not identical. Experimental and clinical evidence also links both metabolites to partially overlapping downstream processes, including oxidative stress, inflammation, endothelial dysfunction, and fibrotic remodeling. These shared pathophysiological responses should be distinguished from convergence of their biosynthetic pathways. This narrative review examines how renal function, metabolic regulation, and nutritional factors influence TMAO and homocysteine biology, emphasizing renal handling, analytical variability, shared downstream mechanisms, and the limitations of isolated measurements. A shift toward context-aware, multiparametric assessment may enhance their interpretation in cardiorenal research, although neither biomarker currently replaces established measures of kidney function.<\/jats:p>","DOI":"10.3390\/ijms27177517","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trimethylamine N-oxide and Homocysteine in Kidney Function and Disease: Distinct Metabolic Origins, Shared Renal Determinants and Pathophysiological Pathways"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8852-7023","authenticated-orcid":false,"given":"Monica","family":"Curr\u00f2","sequence":"first","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0644-8418","authenticated-orcid":false,"given":"Maria Paola","family":"Bertuccio","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Ientile","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8593-9495","authenticated-orcid":false,"given":"Daniela","family":"Caccamo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e004947","DOI":"10.1161\/JAHA.116.004947","article-title":"Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies","volume":"6","author":"Heianza","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"(2005). Homocysteine Lowering Trialists\u2019 Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: A meta-analysis of the randomized trials. Am. J. Clin. Nutr., 82, 806\u2013812.","DOI":"10.1093\/ajcn\/82.4.806"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Homocysteine Studies Collaboration (2002). Homocysteine and risk of ischemic heart disease and stroke: A meta-analysis. JAMA, 288, 2015\u20132022.","DOI":"10.1001\/jama.288.16.2015"},{"key":"ref_4","first-page":"53","article-title":"Homocysteine metabolism in renal failure","volume":"7","author":"Perna","year":"2004","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Saija, C., Curro, M., Ientile, R., Caccamo, D., and Bertuccio, M.P. (2025). Impact of Alterations in Homocysteine, Asymmetric Dimethylarginine and Vitamins-Related Pathways in Some Neurodegenerative Diseases: A Narrative Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083672"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","article-title":"Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk","volume":"368","author":"Tang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2525403","DOI":"10.1080\/07853890.2025.2525403","article-title":"Trimethylamine-N-oxide formation, the bacterial taxa involved and intervention strategies to reduce its concentration in the human body","volume":"57","author":"Vital","year":"2025","journal-title":"Ann. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Amaritei, O., Mierlan, O.L., Dinu, C.A., Chiscop, I., Matei, M.N., Gutu, C., and Gurau, G. (2025). TMAO and Cardiovascular Disease: Exploring Its Potential as a Biomarker. Medicina, 61.","DOI":"10.3390\/medicina61101767"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.nutr.19.1.217","article-title":"Homocysteine metabolism","volume":"19","author":"Selhub","year":"1999","journal-title":"Annu. Rev. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev.med.60.041807.123308","article-title":"The treatment of hyperhomocysteinemia","volume":"60","author":"Maron","year":"2009","journal-title":"Annu. Rev. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1681\/ASN.2014111063","article-title":"Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden","volume":"27","author":"Stubbs","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13781","DOI":"10.1038\/s41598-017-13739-9","article-title":"TMAO is Associated with Mortality: Impact of Modestly Impaired Renal Function","volume":"7","author":"Gruppen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ribeiro, M., Kemp, J.A., Cardozo, L., Vargas, D., Ribeiro-Alves, M., Stenvinkel, P., and Mafra, D. (2024). Trimethylamine N-Oxide (TMAO) Plasma Levels in Patients with Different Stages of Chronic Kidney Disease. Toxins, 17.","DOI":"10.3390\/toxins17010015"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lei, Y., Jiang, J., Chen, L., Fang, Q., Li, C., Fei, Y., Qu, S., Xia, Z., Ning, Y., and He, M. (2025). Utility of trimethylamine N-oxide (TMAO) as a biomarker for risk stratification in chronic kidney disease: A multicenter observational study. BMC Nephrol., 27.","DOI":"10.1186\/s12882-025-04625-y"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2575434","DOI":"10.1080\/0886022X.2025.2575434","article-title":"Gut microbiota-derived TMAO drives the kidney-bone-vascular axis in chronic kidney disease complications","volume":"47","author":"Lei","year":"2025","journal-title":"Ren. Fail."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Su, J.Q., Wu, X.Q., Wang, Q., Xie, B.Y., Xiao, C.Y., Su, H.Y., Tang, J.X., and Yao, C.W. (2025). The microbial metabolite trimethylamine N-oxide and the kidney diseases. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1488264"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1159\/000484623","article-title":"Trimethylamine-N-Oxide Instigates NLRP3 Inflammasome Activation and Endothelial Dysfunction","volume":"44","author":"Boini","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Querio, G., Antoniotti, S., Geddo, F., Levi, R., and Gallo, M.P. (2023). Modulation of Endothelial Function by TMAO, a Gut Microbiota-Derived Metabolite. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065806"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bbrc.2016.11.017","article-title":"Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome","volume":"481","author":"Sun","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, B., Qiu, J., Lian, J., Yang, X., and Zhou, J. (2021). Gut Metabolite Trimethylamine-N-Oxide in Atherosclerosis: From Mechanism to Therapy. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.723886"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2326409817698994","DOI":"10.1177\/2326409817698994","article-title":"The Link Between Hyperhomocysteinemia and Hypomethylation:Implications for Cardiovascular Disease","volume":"5","author":"Barroso","year":"2017","journal-title":"J. Inborn Errors Metab. Screen."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000437098","article-title":"Homocysteine-Induced Endothelial Dysfunction","volume":"67","author":"Lai","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2457527","DOI":"10.1080\/07853890.2025.2457527","article-title":"Role of hyperhomocysteinemia in atherosclerosis: From bench to bedside","volume":"57","author":"Tian","year":"2025","journal-title":"Ann. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2174\/1389200052997357","article-title":"Mechanisms of increased vascular oxidant stress in hyperhomocys-teinemia and its impact on endothelial function","volume":"6","author":"Weiss","year":"2005","journal-title":"Curr. Drug Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1111\/bph.13988","article-title":"Hyperhomocysteinaemia and vascular injury: Advances in mechanisms and drug targets","volume":"175","author":"Fu","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1111\/j.1523-1755.2004.00510.x","article-title":"Hyperhomocysteinemia activates NF-kappaB and inducible nitric oxide synthase in the kidney","volume":"65","author":"Zhang","year":"2004","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10545-010-9088-4","article-title":"Choline and betaine in health and disease","volume":"34","author":"Ueland","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1007\/s00467-016-3527-x","article-title":"The gut-kidney axis","volume":"32","author":"Evenepoel","year":"2017","journal-title":"Pediatr. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ki.2012.345","article-title":"Chronic kidney disease alters intestinal microbial flora","volume":"83","author":"Vaziri","year":"2013","journal-title":"Kidney Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1681\/ASN.2013080905","article-title":"The gut microbiome, kidney disease, and targeted interventions","volume":"25","author":"Ramezani","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1146\/annurev.nutr.24.012003.132418","article-title":"Sulfur amino acid metabolism: Pathways for production and removal of homocysteine and cysteine","volume":"24","author":"Stipanuk","year":"2004","journal-title":"Annu. Rev. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2741\/s70","article-title":"Homocysteine, vitamin determinants and neurological diseases","volume":"2","author":"Ientile","year":"2010","journal-title":"Front. Biosci. (Sch. Ed.)"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1124\/dmd.118.081646","article-title":"Decreased Kidney Function Is Associated with Enhanced Hepatic Flavin Monooxygenase Activity and Increased Circulating Trimethylamine N-Oxide Concentrations in Mice","volume":"46","author":"Johnson","year":"2018","journal-title":"Drug Metab. Dispos."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1146\/annurev-med-060513-093205","article-title":"The gut microbial endocrine organ: Bacterially derived signals driving cardiometabolic diseases","volume":"66","author":"Brown","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lyon, P., Strippoli, V., Fang, B., and Cimmino, L. (2020). B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease. Nutrients, 12.","DOI":"10.3390\/nu12092867"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pelletier, C.C., Croyal, M., Ene, L., Aguesse, A., Billon-Crossouard, S., Krempf, M., Lemoine, S., Guebre-Egziabher, F., Juillard, L., and Soulage, C.O. (2019). Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate. Toxins, 11.","DOI":"10.3390\/toxins11110635"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1021\/acs.molpharmaceut.6b00937","article-title":"Identification and Characterization of Trimethylamine-N-oxide Uptake and Efflux Transporters","volume":"14","author":"Teft","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1016\/j.xphs.2017.04.067","article-title":"Involvement of Organic Cation Transporters in the Kinetics of Trimethylamine N-oxide","volume":"106","author":"Miyake","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6659","DOI":"10.1038\/s41598-018-25139-8","article-title":"Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO)","volume":"8","author":"Gessner","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e002767","DOI":"10.1161\/JAHA.115.002767","article-title":"Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-kappaB","volume":"5","author":"Seldin","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1046\/j.1523-1755.1998.00983.x","article-title":"No net renal extraction of homocysteine in fasting humans","volume":"54","author":"Donker","year":"1998","journal-title":"Kidney Int."},{"key":"ref_43","first-page":"129","article-title":"Homocysteine altered ROS generation and NO accumulation in endothelial cells","volume":"46","author":"Tsen","year":"2003","journal-title":"Chin. J. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kaplan, P., Tatarkova, Z., Sivonova, M.K., Racay, P., and Lehotsky, J. (2020). Homocysteine and Mitochondria in Cardiovascular and Cerebrovascular Systems. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207698"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00109-005-0679-8","article-title":"Intracellular S-adenosylhomocysteine increased levels are associated with DNA hypomethylation in HUVEC","volume":"83","author":"Castro","year":"2005","journal-title":"J. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.1016\/j.apsb.2025.09.012","article-title":"Emerging epigenetic modifications in renal fibrosis: From mechanisms to treatments","volume":"15","author":"Suo","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.7754\/Clin.Lab.2025.250335","article-title":"Progress in the Mechanism of Hyperhomocysteinemia-Induced Renal Injury","volume":"71","author":"Zhang","year":"2025","journal-title":"Clin. Lab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1046\/j.1523-1755.2003.00924.x","article-title":"Review on uremic toxins: Classification, concentration, and interindividual variability","volume":"63","author":"Vanholder","year":"2003","journal-title":"Kidney Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1161\/CIRCRESAHA.116.305360","article-title":"Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease","volume":"116","author":"Tang","year":"2015","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1681\/ASN.0000000000000344","article-title":"The Gut Microbial Metabolite Trimethylamine N -oxide, Incident CKD, and Kidney Function Decline","volume":"35","author":"Wang","year":"2024","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Hai, X., Landeras, V., Dobre, M.A., DeOreo, P., Meyer, T.W., and Hostetter, T.H. (2015). Mechanism of Prominent Trimethylamine Oxide (TMAO) Accumulation in Hemodialysis Patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143731"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Missailidis, C., Hallqvist, J., Qureshi, A.R., Barany, P., Heimburger, O., Lindholm, B., Stenvinkel, P., and Bergman, P. (2016). Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0141738"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1161\/CIRCULATIONAHA.105.570127","article-title":"Relationship between homocysteine and mortality in chronic kidney disease","volume":"113","author":"Menon","year":"2006","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1017\/S0007114511007033","article-title":"Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: A meta-analysis of randomised, controlled trials","volume":"108","author":"Pan","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1001\/jama.298.10.1163","article-title":"Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: A randomized controlled trial","volume":"298","author":"Jamison","year":"2007","journal-title":"JAMA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1093\/ajcn\/82.2.442","article-title":"Biochemical indicators of B vitamin status in the US population after folic acid fortification: Results from the National Health and Nutrition Examination Survey 1999-2000","volume":"82","author":"Pfeiffer","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"938S","DOI":"10.3945\/jn.112.172858","article-title":"The CDC\u2019s Second National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population is a valuable tool for researchers and policy makers","volume":"143","author":"Pfeiffer","year":"2013","journal-title":"J. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1373\/clinchem.2003.021634","article-title":"Facts and recommendations about total homocysteine determinations: An expert opinion","volume":"50","author":"Refsum","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1093\/clinchem\/39.9.1764","article-title":"Total homocysteine in plasma or serum: Methods and clinical applications","volume":"39","author":"Ueland","year":"1993","journal-title":"Clin. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e02481","DOI":"10.1128\/mBio.02481-14","article-title":"Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide","volume":"6","author":"Romano","year":"2015","journal-title":"mBio"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.tem.2016.10.005","article-title":"Trimethylamine-N-Oxide: Friend, Foe, or Simply Caught in the Cross-Fire?","volume":"28","author":"Cho","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ab.2014.03.016","article-title":"Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry","volume":"455","author":"Wang","year":"2014","journal-title":"Anal. Biochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1093\/clinchem\/41.7.991","article-title":"Rapid, fully automated measurement of plasma homocyst(e)ine with the Abbott IMx analyzer","volume":"41","author":"Shipchandler","year":"1995","journal-title":"Clin. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Perla-Kajan, J., and Jakubowski, H. (2019). Dysregulation of Epigenetic Mechanisms of Gene Expression in the Pathologies of Hyperhomocysteinemia. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133140"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"110521","DOI":"10.1016\/j.jbc.2025.110521","article-title":"Gut microbiota-derived metabolite trimethylamine N-oxide alters the host epigenome through inhibition of S-adenosylhomocysteine hydrolase","volume":"301","author":"Han","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ren, L., Pushpakumar, S., Almarshood, H., Das, S.K., and Sen, U. (2024). Epigenetic DNA Methylation and Protein Homocysteinylation: Key Players in Hypertensive Renovascular Damage. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111599"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1161\/hc4601.098514","article-title":"Homocysteine impairs the nitric oxide synthase pathway: Role of asymmetric dimethylarginine","volume":"104","author":"Stuhlinger","year":"2001","journal-title":"Circulation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.jare.2024.08.009","article-title":"Short-chain fatty acid butyrate against TMAO activating endoplasmic-reticulum stress and PERK\/IRE1-axis with reducing atrial arrhythmia","volume":"73","author":"Cheng","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"130900","DOI":"10.1016\/j.bbagen.2025.130900","article-title":"Trimethylamine N-oxide participates in human diseases by causing endoplasmic reticulum stress","volume":"1870","author":"Kumari","year":"2026","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"108604","DOI":"10.1016\/j.pharmthera.2024.108604","article-title":"Protein-rich foods, sea foods, and gut microbiota amplify immune responses in chronic diseases and cancers\u2014Targeting PERK as a novel therapeutic strategy for chronic inflammatory diseases, neurodegenerative disorders, and cancer","volume":"255","author":"Saaoud","year":"2024","journal-title":"Pharmacol. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s12964-023-01288-w","article-title":"Defective quality control autophagy in Hyperhomocysteinemia promotes ER stress and consequent neuronal apoptosis through proteotoxicity","volume":"21","author":"Kaur","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.3892\/mmr.2016.5733","article-title":"Upregulation of DAPK contributes to homocysteine-induced endothelial apoptosis via the modulation of Bcl2\/Bax and activation of caspase 3","volume":"14","author":"Tian","year":"2016","journal-title":"Mol. Med. 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