Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Systematic Review Article

Trimethylamine N-Oxide as a Potential Risk Factor for Non-communicable Diseases: A Systematic Review

Author(s): Zahra Hoseini-Tavassol, Hanieh-Sadat Ejtahed, Bagher Larijani and Shirin Hasani-Ranjbar*

Volume 23, Issue 5, 2023

Published on: 21 December, 2022

Page: [617 - 632] Pages: 16

DOI: 10.2174/1871530323666221103120410

Price: $65

Abstract

Background: Trimethylamine N-Oxide (TMAO), as a gut microbiota-derived metabolite, has been associated with a number of chronic diseases like cardiovascular diseases.

Objective: Considering the increasing prevalence of non-communicable diseases (NCDs), we conducted a systematic review to discuss the TMAO association with NCDs.

Methods: A comprehensive search has been conducted on PubMed, Web of Science, and Scopus databases up to December, 2020. The inclusion criteria were all related observational studies that surveyed the association between TMAO levels and non-communicable diseases. Interventional studies, animal experiments, reviews, case reports, letters, congress abstracts, and studies that were not published in English were excluded. Moreover, related review studies were separately discussed.

Results: Within 2191 recorded studies, 99 cross-sectional, case-control and cohort studies met the inclusion criteria. The most common diseases associated with TMAO levels are cardiovascular diseases, diabetes, kidney disease, stroke, inflammatory diseases, neurological disorders, and cancer. Elevated TMAO levels as a consequence of alteration in gut microbiota composition and dietary intake can lead to the incidence of NCDs. The high levels of TMAO can disrupt the homeostasis of glucose and lipids and induce inflammation that leads to serious NCDs.

Conclusion: There is a dose-response relationship between TMAO levels and NCDs progression. Therefore, it can be studied as a therapeutic target or prognostic biomarker for dealing with NCDs.

Graphical Abstract

[1]
Boutayeb, A.; Boutayeb, S. The burden of non communicable diseases in developing countries. Int. J. Equity Health, 2005, 4(1), 2.
[http://dx.doi.org/10.1186/1475-9276-4-2] [PMID: 15651987]
[2]
Finlay, B.B.; Humans, C. Are noncommunicable diseases communicable? Science, 2020, 367(6475), 250-251.
[http://dx.doi.org/10.1126/science.aaz3834] [PMID: 31949069]
[3]
Stanaway, J.D.; Afshin, A.; Gakidou, E.; Lim, S.S.; Abate, D.; Abate, K.H.; Abbafati, C.; Abbasi, N.; Abbastabar, H.; Abd-Allah, F.; Abdela, J.; Abdelalim, A.; Abdollahpour, I.; Abdulkader, R.S.; Abebe, M.; Abebe, Z.; Abera, S.F.; Abil, O.Z.; Abraha, H.N.; Abrham, A.R.; Abu, R.L.J.; Abu, R.N.M.E.; Accrombessi, M.M.K.; Acharya, D.; Acharya, P.; Adamu, A.A.; Adane, A.A.; Adebayo, O.M.; Adedoyin, R.A.; Adekanmbi, V.; Ademi, Z.; Adetokunboh, O.O.; Adib, M.G.; Admasie, A.; Adsuar, J.C.; Afanvi, K.A.; Afarideh, M.; Agarwal, G.; Aggarwal, A.; Aghayan, S.A.; Agrawal, A.; Agrawal, S.; Ahmadi, A.; Ahmadi, M.; Ahmadieh, H.; Ahmed, M.B.; Aichour, A.N.; Aichour, I.; Aichour, M.T.E.; Akbari, M.E.; Akinyemiju, T.; Akseer, N.; Al-Aly, Z.; Al-Eyadhy, A.; Al-Mekhlafi, H.M.; Alahdab, F.; Alam, K.; Alam, S.; Alam, T.; Alashi, A.; Alavian, S.M.; Alene, K.A.; Ali, K.; Ali, S.M.; Alijanzadeh, M.; Alizadeh, N.R.; Aljunid, S.M.; Alkerwi, A.; Alla, F.; Alsharif, U.; Altirkawi, K.; Alvis, G.N.; Amare, A.T.; Ammar, W.; Anber, N.H.; Anderson, J.A.; Andrei, C.L.; Androudi, S.; Animut, M.D.; Anjomshoa, M.; Ansha, M.G.; Antó, J.M.; Antonio, C.A.T.; Anwari, P.; Appiah, L.T.; Appiah, S.C.Y.; Arabloo, J.; Aremu, O.; Ärnlöv, J.; Artaman, A.; Aryal, K.K.; Asayesh, H.; Ataro, Z.; Ausloos, M.; Avokpaho, E.F.G.A.; Awasthi, A.; Ayala Quintanilla, B.P.; Ayer, R.; Ayuk, T.B.; Azzopardi, P.S.; Babazadeh, A.; Badali, H.; Badawi, A.; Balakrishnan, K.; Bali, A.G.; Ball, K.; Ballew, S.H.; Banach, M.; Banoub, J.A.M.; Barac, A.; Barker, C.S.L.; Bärnighausen, T.W.; Barrero, L.H.; Basu, S.; Baune, B.T.; Bazargan, H.S.; Bedi, N.; Beghi, E.; Behzadifar, M.; Behzadifar, M.; Béjot, Y.; Bekele, B.B.; Bekru, E.T.; Belay, E.; Belay, Y.A.; Bell, M.L.; Bello, A.K.; Bennett, D.A.; Bensenor, I.M.; Bergeron, G.; Berhane, A.; Bernabe, E.; Bernstein, R.S.; Beuran, M.; Beyranvand, T.; Bhala, N.; Bhalla, A.; Bhattarai, S.; Bhutta, Z.A.; Biadgo, B.; Bijani, A.; Bikbov, B.; Bilano, V.; Bililign, N.; Bin Sayeed, M.S.; Bisanzio, D.; Biswas, T.; Bjørge, T.; Blacker, B.F.; Bleyer, A.; Borschmann, R.; Bou, O.I.R.; Boufous, S.; Bourne, R.; Brady, O.J.; Brauer, M.; Brazinova, A.; Breitborde, N.J.K.; Brenner, H.; Briko, A.N.; Britton, G.; Brugha, T.; Buchbinder, R.; Burnett, R.T.; Busse, R.; Butt, Z.A.; Cahill, L.E.; Cahuana, H.L.; Campos, N.I.R.; Cárdenas, R.; Carreras, G.; Carrero, J.J.; Carvalho, F.; Castañeda, O.C.A.; Castillo, R.J.; Castro, F.; Catalá, L.F.; Causey, K.; Cercy, K.M.; Cerin, E.; Chaiah, Y.; Chang, H.Y.; Chang, J.C.; Chang, K.L.; Charlson, F.J.; Chattopadhyay, A.; Chattu, V.K.; Chee, M.L.; Cheng, C.Y.; Chew, A.; Chiang, P.P.C.; Chimed, O.O.; Chin, K.L.; Chitheer, A.; Choi, J.Y.J.; Chowdhury, R.; Christensen, H.; Christopher, D.J.; Chung, S-C.; Cicuttini, F.M.; Cirillo, M.; Cohen, A.J.; Collado, M.D.; Cooper, C.; Cooper, O.R.; Coresh, J.; Cornaby, L.; Cortesi, P.A.; Cortinovis, M.; Costa, M.; Cousin, E.; Criqui, M.H.; Cromwell, E.A.; Cundiff, D.K.; Daba, A.K.; Dachew, B.A.; Dadi, A.F.; Damasceno, A.A.M.; Dandona, L.; Dandona, R.; Darby, S.C.; Dargan, P.I.; Daryani, A.; Das Gupta, R.; Das Neves, J.; Dasa, T.T.; Dash, A.P.; Davitoiu, D.V.; Davletov, K.; De La Cruz, G.V.; De La Hoz, F.P.; De Leo, D.; De Neve, J-W.; Degenhardt, L.; Deiparine, S.; Dellavalle, R.P.; Demoz, G.T.; Denova, G.E.; Deribe, K.; Dervenis, N.; Deshpande, A.; Des Jarlais, D.C.; Dessie, G.A.; Deveber, G.A.; Dey, S.; Dharmaratne, S.D.; Dhimal, M.; Dinberu, M.T.; Ding, E.L.; Diro, H.D.; Djalalinia, S.; Do, H.P.; Dokova, K.; Doku, D.T.; Doyle, K.E.; Driscoll, T.R.; Dubey, M.; Dubljanin, E.; Duken, E.E.; Duncan, B.B.; Duraes, A.R.; Ebert, N.; Ebrahimi, H.; Ebrahimpour, S.; Edvardsson, D.; Effiong, A.; Eggen, A.E.; El Bcheraoui, C.; El-Khatib, Z.; Elyazar, I.R.; Enayati, A.; Endries, A.Y.; Er, B.; Erskine, H.E.; Eskandarieh, S.; Esteghamati, A.; Estep, K.; Fakhim, H.; Faramarzi, M.; Fareed, M.; Farid, T.A.; Farinha, C.S.E.; Farioli, A.; Faro, A.; Farvid, M.S.; Farzaei, M.H.; Fatima, B.; Fay, K.A.; Fazaeli, A.A.; Feigin, V.L.; Feigl, A.B.; Fereshtehnejad, S.M.; Fernandes, E.; Fernandes, J.C.; Ferrara, G.; Ferrari, A.J.; Ferreira, M.L.; Filip, I.; Finger, J.D.; Fischer, F.; Foigt, N.A.; Foreman, K.J.; Fukumoto, T.; Fullman, N.; Fürst, T.; Furtado, J.M.; Futran, N.D.; Gall, S.; Gallus, S.; Gamkrelidze, A.; Ganji, M.; Garcia, B.A.L.; Gardner, W.M.; Gebre, A.K.; Gebremedhin, A.T.; Gebremichael, T.G.; Gelano, T.F.; Geleijnse, J.M.; Geramo, Y.C.D.; Gething, P.W.; Gezae, K.E.; Ghadimi, R.; Ghadiri, K.; Ghasemi, F.K.; Ghasemi, K.M.; Ghimire, M.; Ghosh, R.; Ghoshal, A.G.; Giampaoli, S.; Gill, P.S.; Gill, T.K.; Gillum, R.F.; Ginawi, I.A.; Giussani, G.; Gnedovskaya, E.V.; Godwin, W.W.; Goli, S.; Gómez, D.H.; Gona, P.N.; Gopalani, S.V.; Goulart, A.C.; Grada, A.; Grams, M.E.; Grosso, G.; Gugnani, H.C.; Guo, Y.; Gupta, R.; Gupta, R.; Gupta, T.; Gutiérrez, R.A.; Gutiérrez, T.D.S.; Haagsma, J.A.; Habtewold, T.D.; Hachinski, V.; Hafezi, N.N.; Hagos, T.B.; Hailegiyorgis, T.T.; Hailu, G.B.; Haj-Mirzaian, A.; Haj-Mirzaian, A.; Hamadeh, R.R.; Hamidi, S.; Handal, A.J.; Hankey, G.J.; Hao, Y.; Harb, H.L.; Harikrishnan, S.; Haro, J.M.; Hassankhani, H.; Hassen, H.Y.; Havmoeller, R.; Hawley, C.N.; Hay, S.I.; Hedayatizadeh-Omran, A.; Heibati, B.; Heidari, B.; Heidari, M.; Hendrie, D.; Henok, A.; Heredia-Pi, I.; Herteliu, C.; Heydarpour, F.; Heydarpour, S.; Hibstu, D.T.; Higazi, T.B.; Hilawe, E.H.; Hoek, H.W.; Hoffman, H.J.; Hole, M.K.; Homaie Rad, E.; Hoogar, P.; Hosgood, H.D.; Hosseini, S.M.; Hosseinzadeh, M.; Hostiuc, M.; Hostiuc, S.; Hoy, D.G.; Hsairi, M.; Hsiao, T.; Hu, G.; Hu, H.; Huang, J.J.; Hussen, M.A.; Huynh, C.K.; Iburg, K.M.; Ikeda, N.; Ilesanmi, O.S.; Iqbal, U.; Irvani, S.S.N.; Irvine, C.M.S.; Islam, S.M.S.; Islami, F.; Jackson, M.D.; Jacobsen, K.H.; Jahangiry, L.; Jahanmehr, N.; Jain, S.K.; Jakovljevic, M.; James, S.L.; Jassal, S.K.; Jayatilleke, A.U.; Jeemon, P.; Jha, R.P.; Jha, V.; Ji, J.S.; Jonas, J.B.; Jonnagaddala, J.; Jorjoran Shushtari, Z.; Joshi, A.; Jozwiak, J.J.; Jürisson, M.; Kabir, Z.; Kahsay, A.; Kalani, R.; Kanchan, T.; Kant, S.; Kar, C.; Karami, M.; Karami Matin, B.; Karch, A.; Karema, C.; Karimi, N.; Karimi, S.M.; Kasaeian, A.; Kassa, D.H.; Kassa, G.M.; Kassa, T.D.; Kassebaum, N.J.; Katikireddi, S.V.; Kaul, A.; Kawakami, N.; Kazemi, Z.; Karyani, A.K.; Kefale, A.T.; Keiyoro, P.N.; Kemp, G.R.; Kengne, A.P.; Keren, A.; Kesavachandran, C.N.; Khader, Y.S.; Khafaei, B.; Khafaie, M.A.; Khajavi, A.; Khalid, N.; Khalil, I.A.; Khan, G.; Khan, M.S.; Khan, M.A.; Khang, Y-H.; Khater, M.M.; Khazaei, M.; Khazaie, H.; Khoja, A.T.; Khosravi, A.; Khosravi, M.H.; Kiadaliri, A.A.; Kiirithio, D.N.; Kim, C-I.; Kim, D.; Kim, Y-E.; Kim, Y.J.; Kimokoti, R.W.; Kinfu, Y.; Kisa, A.; Kissimova-Skarbek, K.; Kivimäki, M.; Knibbs, L.D.; Knudsen, A.K.S.; Kochhar, S.; Kokubo, Y.; Kolola, T.; Kopec, J.A.; Kosen, S.; Koul, P.A.; Koyanagi, A.; Kravchenko, M.A.; Krishan, K.; Krohn, K.J.; Kromhout, H.; Kuate Defo, B.; Kucuk Bicer, B.; Kumar, G.A.; Kumar, M.; Kuzin, I.; Kyu, H.H.; Lachat, C.; Lad, D.P.; Lad, S.D.; Lafranconi, A.; Lalloo, R.; Lallukka, T.; Lami, F.H.; Lang, J.J.; Lansingh, V.C.; Larson, S.L.; Latifi, A.; Lazarus, J.V.; Lee, P.H.; Leigh, J.; Leili, M.; Leshargie, C.T.; Leung, J.; Levi, M.; Lewycka, S.; Li, S.; Li, Y.; Liang, J.; Liang, X.; Liao, Y.; Liben, M.L.; Lim, L-L.; Linn, S.; Liu, S.; Lodha, R.; Logroscino, G.; Lopez, A.D.; Lorkowski, S.; Lotufo, P.A.; Lozano, R.; Lucas, T.C.D.; Lunevicius, R.; Ma, S.; Macarayan, E.R.K.; Machado, Í.E.; Madotto, F.; Mai, H.T.; Majdan, M.; Majdzadeh, R.; Majeed, A.; Malekzadeh, R.; Malta, D.C.; Mamun, A.A.; Manda, A-L.; Manguerra, H.; Mansournia, M.A.; Mantovani, L.G.; Maravilla, J.C.; Marcenes, W.; Marks, A.; Martin, R.V.; Martins, S.C.O.; Martins, M.F.R.; März, W.; Marzan, M.B.; Massenburg, B.B.; Mathur, M.R.; Mathur, P.; Matsushita, K.; Maulik, P.K.; Mazidi, M.; McAlinden, C.; McGrath, J.J.; McKee, M.; Mehrotra, R.; Mehta, K.M.; Mehta, V.; Meier, T.; Mekonnen, F.A.; Melaku, Y.A.; Melese, A.; Melku, M.; Memiah, P.T.N.; Memish, Z.A.; Mendoza, W.; Mengistu, D.T.; Mensah, G.A.; Mensink, G.B.M.; Mereta, S.T.; Meretoja, A.; Meretoja, T.J.; Mestrovic, T.; Mezgebe, H.B.; Miazgowski, B.; Miazgowski, T.; Millear, A.I.; Miller, T.R.; Miller-Petrie, M.K.; Mini, G.K.; Mirarefin, M.; Mirica, A.; Mirrakhimov, E.M.; Misganaw, A.T.; Mitiku, H.; Moazen, B.; Mohajer, B.; Mohammad, K.A.; Mohammadi, M.; Mohammadifard, N.; Mohammadnia-Afrouzi, M.; Mohammed, S.; Mohebi, F.; Mokdad, A.H.; Molokhia, M.; Momeniha, F.; Monasta, L.; Moodley, Y.; Moradi, G.; Moradi-Lakeh, M.; Moradinazar, M.; Moraga, P.; Morawska, L.; Morgado-Da-Costa, J.; Morrison, S.D.; Moschos, M.M.; Mouodi, S.; Mousavi, S.M.; Mozaffarian, D.; Mruts, K.B.; Muche, A.A.; Muchie, K.F.; Mueller, U.O.; Muhammed, O.S.; Mukhopadhyay, S.; Muller, K.; Musa, K.I.; Mustafa, G.; Nabhan, A.F.; Naghavi, M.; Naheed, A.; Nahvijou, A.; Naik, G.; Naik, N.; Najafi, F.; Nangia, V.; Nansseu, J.R.; Nascimento, B.R.; Neal, B.; Neamati, N.; Negoi, I.; Negoi, R.I.; Neupane, S.; Newton, C.R.J.; Ngunjiri, J.W.; Nguyen, A.Q.; Nguyen, G.; Nguyen, H.T.; Nguyen, H.L.T.; Nguyen, H.T.; Nguyen, M.; Nguyen, N.B.; Nichols, E.; Nie, J.; Ningrum, D.N.A.; Nirayo, Y.L.; Nishi, N.; Nixon, M.R.; Nojomi, M.; Nomura, S.; Norheim, O.F.; Noroozi, M.; Norrving, B.; Noubiap, J.J.; Nouri, H.R.; Nourollahpour Shiadeh, M.; Nowroozi, M.R.; Nsoesie, E.O.; Nyasulu, P.S.; Obermeyer, C.M.; Odell, C.M.; Ofori-Asenso, R.; Ogbo, F.A.; Oh, I-H.; Oladimeji, O.; Olagunju, A.T.; Olagunju, T.O.; Olivares, P.R.; Olsen, H.E.; Olusanya, B.O.; Olusanya, J.O.; Ong, K.L.; Ong, S.K.; Oren, E.; Orpana, H.M.; Ortiz, A.; Ota, E.; Otstavnov, S.S.; Øverland, S.; Owolabi, M.O.; P A, M.; Pacella, R.; Pakhare, A.P.; Pakpour, A.H.; Pana, A.; Panda-Jonas, S.; Park, E-K.; Parry, C.D.H.; Parsian, H.; Patel, S.; Pati, S.; Patil, S.T.; Patle, A.; Patton, G.C.; Paudel, D.; Paulson, K.R.; Paz Ballesteros, W.C.; Pearce, N.; Pereira, A.; Pereira, D.M.; Perico, N.; Pesudovs, K.; Petzold, M.; Pham, H.Q.; Phillips, M.R.; Pillay, J.D.; Piradov, M.A.; Pirsaheb, M.; Pischon, T.; Pishgar, F.; Plana-Ripoll, O.; Plass, D.; Polinder, S.; Polkinghorne, K.R.; Postma, M.J.; Poulton, R.; Pourshams, A.; Poustchi, H.; Prabhakaran, D.; Prakash, S.; Prasad, N.; Purcell, C.A.; Purwar, M.B.; Qorbani, M.; Radfar, A.; Rafay, A.; Rafiei, A.; Rahim, F.; Rahimi, Z.; Rahimi-Movaghar, A.; Rahimi-Movaghar, V.; Rahman, M.; Rahman, M.H.; Rahman, M.A.; Rai, R.K.; Rajati, F.; Rajsic, S.; Raju, S.B.; Ram, U.; Ranabhat, C.L.; Ranjan, P.; Rath, G.K.; Rawaf, D.L.; Rawaf, S.; Reddy, K.S.; Rehm, C.D.; Rehm, J.; Reiner, R.C., Jr; Reitsma, M.B.; Remuzzi, G.; Renzaho, A.M.N.; Resnikoff, S.; Reynales, S.L.M.; Rezaei, S.; Ribeiro, A.L.P.; Rivera, J.A.; Roba, K.T.; Rodríguez-Ramírez, S.; Roever, L.; Román, Y.; Ronfani, L.; Roshandel, G.; Rostami, A.; Roth, G.A.; Rothenbacher, D.; Roy, A.; Rubagotti, E.; Rushton, L.; Sabanayagam, C.; Sachdev, P.S.; Saddik, B.; Sadeghi, E.; Saeedi Moghaddam, S.; Safari, H.; Safari, Y.; Safari-Faramani, R.; Safdarian, M.; Safi, S.; Safiri, S.; Sagar, R.; Sahebkar, A.; Sahraian, M.A.; Sajadi, H.S.; Salam, N.; Salamati, P.; Saleem, Z.; Salimi, Y.; Salimzadeh, H.; Salomon, J.A.; Salvi, D.D.; Salz, I.; Samy, A.M.; Sanabria, J.; Sanchez-Niño, M.D.; Sánchez-Pimienta, T.G.; Sanders, T.; Sang, Y.; Santomauro, D.F.; Santos, I.S.; Santos, J.V.; Santric Milicevic, M.M.; Sao Jose, B.P.; Sardana, M.; Sarker, A.R.; Sarmiento-Suárez, R.; Sarrafzadegan, N.; Sartorius, B.; Sarvi, S.; Sathian, B.; Satpathy, M.; Sawant, A.R.; Sawhney, M.; Saylan, M.; Sayyah, M.; Schaeffner, E.; Schmidt, M.I.; Schneider, I.J.C.; Schöttker, B.; Schutte, A.E.; Schwebel, D.C.; Schwendicke, F.; Scott, J.G.; Seedat, S.; Sekerija, M.; Sepanlou, S.G.; Serre, M.L.; Serván-Mori, E.; Seyedmousavi, S.; Shabaninejad, H.; Shaddick, G.; Shafieesabet, A.; Shahbazi, M.; Shaheen, A.A.; Shaikh, M.A.; Shamah Levy, T.; Shams-Beyranvand, M.; Shamsi, M.; Sharafi, H.; Sharafi, K.; Sharif, M.; Sharif-Alhoseini, M.; Sharifi, H.; Sharma, J.; Sharma, M.; Sharma, R.; She, J.; Sheikh, A.; Shi, P.; Shibuya, K.; Shiferaw, M.S.; Shigematsu, M.; Shin, M-J.; Shiri, R.; Shirkoohi, R.; Shiue, I.; Shokraneh, F.; Shoman, H.; Shrime, M.G.; Shupler, M.S.; Si, S.; Siabani, S.; Sibai, A.M.; Siddiqi, T.J.; Sigfusdottir, I.D.; Sigurvinsdottir, R.; Silva, D.A.S.; Silva, J.P.; Silveira, D.G.A.; Singh, J.A.; Singh, N.P.; Singh, V.; Sinha, D.N.; Skiadaresi, E.; Skirbekk, V.; Smith, D.L.; Smith, M.; Sobaih, B.H.; Sobhani, S.; Somayaji, R.; Soofi, M.; Sorensen, R.J.D.; Soriano, J.B.; Soyiri, I.N.; Spinelli, A.; Sposato, L.A.; Sreeramareddy, C.T.; Srinivasan, V.; Starodubov, V.I.; Steckling, N.; Stein, D.J.; Stein, M.B.; Stevanovic, G.; Stockfelt, L.; Stokes, M.A.; Sturua, L.; Subart, M.L.; Sudaryanto, A.; Sufiyan, M.B.; Sulo, G.; Sunguya, B.F.; Sur, P.J.; Sykes, B.L.; Szoeke, C.E.I.; Tabarés, S.R.; Tabuchi, T.; Tadakamadla, S.K.; Takahashi, K.; Tandon, N.; Tassew, S.G.; Tavakkoli, M.; Taveira, N.; Tehrani, B.A.; Tekalign, T.G.; Tekelemedhin, S.W.; Tekle, M.G.; Temesgen, H.; Temsah, M.H.; Temsah, O.; Terkawi, A.S.; Tessema, B.; Teweldemedhin, M.; Thankappan, K.R.; Theis, A.; Thirunavukkarasu, S.; Thomas, H.J.; Thomas, M.L.; Thomas, N.; Thurston, G.D.; Tilahun, B.; Tillmann, T.; To, Q.G.; Tobollik, M.; Tonelli, M.; Topor, M.R.; Torre, A.E.; Tortajada, G.M.; Touvier, M.; Tovani, P.M.R.; Towbin, J.A.; Tran, B.X.; Tran, K.B.; Truelsen, T.C.; Truong, N.T.; Tsadik, A.G.; Tudor Car, L.; Tuzcu, E.M.; Tymeson, H.D.; Tyrovolas, S.; Ukwaja, K.N.; Ullah, I.; Updike, R.L.; Usman, M.S.; Uthman, O.A.; Vaduganathan, M.; Vaezi, A.; Valdez, P.R.; Van Donkelaar, A.; Varavikova, E.; Varughese, S.; Vasankari, T.J.; Venkateswaran, V.; Venketasubramanian, N.; Villafaina, S.; Violante, F.S.; Vladimirov, S.K.; Vlassov, V.; Vollset, S.E.; Vos, T.; Vosoughi, K.; Vu, G.T.; Vujcic, I.S.; Wagnew, F.S.; Waheed, Y.; Waller, S.G.; Walson, J.L.; Wang, Y.; Wang, Y.; Wang, Y.P.; Weiderpass, E.; Weintraub, R.G.; Weldegebreal, F.; Werdecker, A.; Werkneh, A.A.; West, J.J.; Westerman, R.; Whiteford, H.A.; Widecka, J.; Wijeratne, T.; Winkler, A.S.; Wiyeh, A.B.; Wiysonge, C.S.; Wolfe, C.D.A.; Wong, T.Y.; Wu, S.; Xavier, D.; Xu, G.; Yadgir, S.; Yadollahpour, A.; Yahyazadeh Jabbari, S.H.; Yamada, T.; Yan, L.L.; Yano, Y.; Yaseri, M.; Yasin, Y.J.; Yeshaneh, A.; Yimer, E.M.; Yip, P.; Yisma, E.; Yonemoto, N.; Yoon, S-J.; Yotebieng, M.; Younis, M.Z.; Yousefifard, M.; Yu, C.; Zaidi, Z.; Zaman, S.B.; Zamani, M.; Zavala, A.L.; Zhang, A.L.; Zhang, H.; Zhang, K.; Zhou, M.; Zimsen, S.R.M.; Zodpey, S.; Murray, C.J.L. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 2018, 392(10159), 1923-1994.
[http://dx.doi.org/10.1016/S0140-6736(18)32225-6] [PMID: 30496105]
[4]
Organization, W.H. Noncommunicable diseases country profiles; , 2018. Available from: https://apps.who.int/iris/handle/10665/274512
[5]
Subramaniam, S.; Fletcher, C. Trimethylamine N-oxide: Breathe new life. Br. J. Pharmacol., 2018, 175(8), 1344-1353.
[http://dx.doi.org/10.1111/bph.13959] [PMID: 28745401]
[6]
Ejtahed, HS.; Soroush, AR.; Angoorani, P.; Larijani, B.; Hasani, RS. Gut microbiota as a target in the pathogenesis of metabolic disorders: A new approach to novel therapeutic agents. Horm. Metab. Res., 2016, 48(6), 349-358.
[http://dx.doi.org/10.1055/s-0042-107792]
[7]
Chen, Y.; Liu, Y.; Zhou, R.; Chen, X.; Wang, C.; Tan, X.; Wang, L.; Zheng, R.; Zhang, H.; Ling, W.; Zhu, H. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults. Sci. Rep., 2016, 6(1), 19076.
[http://dx.doi.org/10.1038/srep19076] [PMID: 26743949]
[8]
Guertin, K.A.; Li, X.S.; Graubard, B.I.; Albanes, D.; Weinstein, S.J.; Goedert, J.J.; Wang, Z.; Hazen, S.L.; Sinha, R. Serum trimethylamine n-oxide, carnitine, choline, and betaine in relation to colorectal cancer risk in the alpha tocopherol, beta carotene cancer prevention study. Cancer Epidemiol. Biomarkers Prev., 2017, 26(6), 945-952.
[http://dx.doi.org/10.1158/1055-9965.EPI-16-0948] [PMID: 28077427]
[9]
Shanahan, F. The gut microbiota—a clinical perspective on lessons learned. Nat. Rev. Gastroenterol. Hepatol., 2012, 9(10), 609-614.
[http://dx.doi.org/10.1038/nrgastro.2012.145] [PMID: 22890109]
[10]
Smirnov, K.S.; Maier, T.V.; Walker, A.; Heinzmann, S.S.; Forcisi, S.; Martinez, I.; Walter, J.; Schmitt, K.P. Challenges of metabolomics in human gut microbiota research. Int. J. Med. Microbiol., 2016, 306(5), 266-279.
[http://dx.doi.org/10.1016/j.ijmm.2016.03.006] [PMID: 27012595]
[11]
Cho, C.E.; Caudill, M.A. Trimethylamine-N-oxide: Friend, foe, or simply caught in the cross-fire? Trends Endocrinol. Metab., 2017, 28(2), 121-130.
[http://dx.doi.org/10.1016/j.tem.2016.10.005] [PMID: 27825547]
[12]
Hoseini, T.Z.; Hasani, R.S. Targeting TMAO and its metabolic pathway for cardiovascular diseases treatment. J. Diabetes Metab. Disord., 2021, 20(1), 1095-1097.
[http://dx.doi.org/10.1007/s40200-021-00819-x] [PMID: 34178875]
[13]
Janeiro, M. Ramírez, M.; Milagro, F.; Martínez, J.; Solas, M. Implication of Trimethylamine N-oxide (TMAO) in disease: Potential biomarker or new therapeutic target. Nutrients, 2018, 10(10), 1398.
[http://dx.doi.org/10.3390/nu10101398] [PMID: 30275434]
[14]
Zhuang, R.; Ge, X.; Han, L.; Yu, P.; Gong, X.; Meng, Q.; Zhang, Y.; Fan, H.; Zheng, L.; Liu, Z.; Zhou, X. Gut microbe–generated metabolite trimethylamine N -oxide and the risk of diabetes: A systematic review and dose-response meta-analysis. Obes. Rev., 2019, 20(6), 883-894.
[http://dx.doi.org/10.1111/obr.12843] [PMID: 30868721]
[15]
Farhangi, M.A.; Vajdi, M.; Asghari, J.M. Gut microbiota-associated metabolite trimethylamine N-Oxide and the risk of stroke: A systematic review and dose–response meta-analysis. Nutr. J., 2020, 19(1), 76.
[http://dx.doi.org/10.1186/s12937-020-00592-2] [PMID: 32731904]
[16]
Yao, M.E.; Liao, P.D.; Zhao, X.J.; Wang, L. Trimethylamine-N-oxide has prognostic value in coronary heart disease: A meta-analysis and dose-response analysis. BMC Cardiovasc. Disord., 2020, 20(1), 7.
[http://dx.doi.org/10.1186/s12872-019-01310-5] [PMID: 31918665]
[17]
Qi, J.; You, T.; Li, J.; Pan, T.; Xiang, L.; Han, Y.; Zhu, L. Circulating trimethylamine N-oxide and the risk of cardiovascular diseases: A systematic review and meta-analysis of 11 prospective cohort studies. J. Cell. Mol. Med., 2018, 22(1), 185-194.
[http://dx.doi.org/10.1111/jcmm.13307] [PMID: 28782886 ]
[18]
Schiattarella, G.G.; Sannino, A.; Toscano, E.; Giugliano, G.; Gargiulo, G.; Franzone, A.; Trimarco, B.; Esposito, G.; Perrino, C. Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: A systematic review and dose-response meta-analysis. Eur. Heart J., 2017, 38(39), 2948-2956.
[http://dx.doi.org/10.1093/eurheartj/ehx342] [PMID: 29020409]
[19]
Ge, X.; Zheng, L.; Zhuang, R.; Yu, P.; Xu, Z.; Liu, G.; Xi, X.; Zhou, X.; Fan, H. The gut microbial metabolite trimethylamine N-oxide and hypertension risk: A systematic review and dose-response meta-analysis. Adv. Nutr., 2020, 11(1), 66-76.
[PMID: 31269204]
[20]
Abbasalizad, F.M.; Vajdi, M. Gut microbiota–associated trimethylamine N-oxide and increased cardiometabolic risk in adults: A systematic review and dose-response meta-analysis. Nutr. Rev., 2020, 79(9), 1022-1042.
[PMID: 33270896]
[21]
Guasti, L.; Galliazzo, S.; Molaro, M.; Visconti, E.; Pennella, B.; Gaudio, G.V.; Lupi, A.; Grandi, A.M.; Squizzato, A. TMAO as a biomarker of cardiovascular events: A systematic review and meta-analysis. Intern. Emerg. Med., 2021, 16(1), 201-207.
[http://dx.doi.org/10.1007/s11739-020-02470-5] [PMID: 32779113]
[22]
Lever, M.; George, P.M.; Slow, S.; Bellamy, D.; Young, J.M.; Ho, M.; McEntyre, C.J.; Elmslie, J.L.; Atkinson, W.; Molyneux, S.L.; Troughton, R.W.; Frampton, C.M.; Richards, A.M.; Chambers, S.T. Betaine and trimethylamine-N-oxide as predictors of cardiovascular outcomes show different patterns in diabetes mellitus: An observational study. PLoS One, 2014, 9(12), e114969.
[http://dx.doi.org/10.1371/journal.pone.0114969] [PMID: 25493436]
[23]
McEntyre, C.J.; Lever, M.; Chambers, S.T.; George, P.M.; Slow, S.; Elmslie, J.L.; Florkowski, C.M.; Lunt, H.; Krebs, J.D. Variation of betaine, N,N- dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine- N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period. Ann. Clin. Biochem., 2015, 52(3), 352-360.
[http://dx.doi.org/10.1177/0004563214545346] [PMID: 25013088]
[24]
Obeid, R.; Awwad, H.M.; Rabagny, Y.; Graeber, S.; Herrmann, W.; Geisel, J. Plasma trimethylamine N-oxide concentration is associated with choline, phospholipids, and methyl metabolism. Am. J. Clin. Nutr., 2016, 103(3), 703-711.
[http://dx.doi.org/10.3945/ajcn.115.121269] [PMID: 26864355]
[25]
Al-Obaide, M.; Singh, R.; Datta, P.; Rewers, F.K.; Salguero, M.; Al-Obaidi, I.; Kottapalli, K.; Vasylyeva, T. Gut microbiota-dependent trimethylamine-N-oxide and serum biomarkers in patients with T2DM and advanced CKD. J. Clin. Med., 2017, 6(9), 86.
[http://dx.doi.org/10.3390/jcm6090086] [PMID: 28925931]
[26]
Shan, Z.; Sun, T.; Huang, H.; Chen, S.; Chen, L.; Luo, C.; Yang, W.; Yang, X.; Yao, P.; Cheng, J.; Hu, F.B.; Liu, L. Association between microbiota-dependent metabolite trimethylamine- N -oxide and type 2 diabetes. Am. J. Clin. Nutr., 2017, 106(3), ajcn157107.
[http://dx.doi.org/10.3945/ajcn.117.157107] [PMID: 28724646]
[27]
Tang, W.H.W.; Wang, Z.; Li, X.S.; Fan, Y.; Li, D.S.; Wu, Y.; Hazen, S.L. Increased trimethylamine N-oxide portends high mortality risk independent of glycemic control in patients with type 2 diabetes mellitus. Clin. Chem., 2017, 63(1), 297-306.
[http://dx.doi.org/10.1373/clinchem.2016.263640] [PMID: 27864387]
[28]
Dong, Z.; Liang, Z.; Guo, M.; Hu, S.; Shen, Z.; Hai, X. The association between plasma levels of trimethylamine N-oxide and the risk of coronary heart disease in Chinese patients with or without type 2 diabetes mellitus. Dis. Markers, 2018, 2018, 1578320.
[http://dx.doi.org/10.1155/2018/1578320] [PMID: 30159101]
[29]
Li, P.; Zhong, C.; Li, S.; Sun, T.; Huang, H.; Chen, X.; Zhu, Y.; Hu, X.; Peng, X.; Zhang, X.; Bao, W.; Shan, Z.; Cheng, J.; Hu, F.B.; Yang, N.; Liu, L. Plasma concentration of trimethylamine-N-oxide and risk of gestational diabetes mellitus. Am. J. Clin. Nutr., 2018, 108(3), 603-610.
[http://dx.doi.org/10.1093/ajcn/nqy116] [PMID: 30535087]
[30]
Papandreou, C.; Bulló, M.; Zheng, Y.; Ruiz, C.M.; Yu, E.; Guasc, F.M.; Toledo, E.; Clish, C.; Corella, D.; Estruch, R.; Ros, E.; Fitó, M.; Arós, F.; Fiol, M.; Lapetra, J.; Serra, M.L.; Gómez, G.E.; Liang, L.; Fragkiadakis, G.A.; Razquin, C.; Hu, F.B.; Salas, S.J. Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial. Am. J. Clin. Nutr., 2018, 108(1), 163-173.
[http://dx.doi.org/10.1093/ajcn/nqy058] [PMID: 29982310]
[31]
Cardona, A.; O’Brien, A.; Bernier, M.C.; Somogyi, A.; Wysocki, V.H.; Smart, S.; He, X.; Ambrosio, G.; Hsueh, W.A.; Raman, S.V. Trimethylamine N-oxide and incident atherosclerotic events in high-risk individuals with diabetes: An accord trial post hoc analysis. BMJ Open Diabetes Res. Care, 2019, 7(1), e000718.
[http://dx.doi.org/10.1136/bmjdrc-2019-000718] [PMID: 31798892]
[32]
Garcia, E.; Osté, M.C.J.; Bennett, D.W.; Jeyarajah, E.J.; Shalaurova, I.; Gruppen, E.G.; Hazen, S.L.; Otvos, J.D.; Bakker, S.J.L.; Dullaart, R.P.F.; Connelly, M.A. High betaine, a trimethylamine N-oxide related metabolite, is prospectively associated with low future risk of type 2 diabetes mellitus in the prevend study. J. Clin. Med., 2019, 8(11), 1813.
[http://dx.doi.org/10.3390/jcm8111813] [PMID: 31683780]
[33]
Huo, X.; Li, J.; Cao, Y.F.; Li, S.N.; Shao, P.; Leng, J.; Li, W.; Liu, J.; Yang, K.; Ma, R.C.W.; Hu, G.; Fang, Z.Z.; Yang, X. Trimethylamine N-oxide metabolites in early pregnancy and risk of gestational diabetes: A nested case-control study. J. Clin. Endocrinol. Metab., 2019, 104(11), 5529-5539.
[http://dx.doi.org/10.1210/jc.2019-00710] [PMID: 31373635]
[34]
Winther, S.A. Øllgaard, J.C.; Tofte, N.; Tarnow, L.; Wang, Z.; Ahluwalia, T.S.; Jorsal, A.; Theilade, S.; Parving, H.H.; Hansen, T.W.; Hazen, S.L.; Pedersen, O.; Rossing, P. Utility of plasma concentration of trimethylamine N-oxide in predicting cardiovascular and renal complications in individuals with type 1 diabetes. Diabetes Care, 2019, 42(8), 1512-1520.
[http://dx.doi.org/10.2337/dc19-0048] [PMID: 31123156]
[35]
Croyal, M.; Saulnier, P.J.; Aguesse, A.; Gand, E.; Ragot, S.; Roussel, R.; Halimi, J.M.; Ducrocq, G.; Cariou, B.; Montaigne, D.; Wargny, M.; Krempf, M.; Hadjadj, S. Plasma trimethylamine N-oxide and risk of cardiovascular events in patients with type 2 diabetes. J. Clin. Endocrinol. Metab., 2020, 105(7), 2371-2380.
[http://dx.doi.org/10.1210/clinem/dgaa188] [PMID: 32301490]
[36]
Roy, S.; Yuzefpolskaya, M.; Nandakumar, R.; Colombo, P.C.; Demmer, R.T. Plasma trimethylamine-N-oxide and impaired glucose regulation: Results from the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS). PLoS One, 2020, 15(1), e0227482.
[http://dx.doi.org/10.1371/journal.pone.0227482] [PMID: 31940332]
[37]
Bain, M.A.; Faull, R.; Fornasini, G.; Milne, R.W.; Evans, A.M. Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis. Nephrol. Dial. Transplant., 2006, 21(5), 1300-1304.
[http://dx.doi.org/10.1093/ndt/gfk056] [PMID: 16401621]
[38]
Mueller, D.M.; Allenspach, M.; Othman, A.; Saely, C.H.; Muendlein, A.; Vonbank, A.; Drexel, H.; Von Eckardstein, A. Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control. Atherosclerosis, 2015, 243(2), 638-644.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.10.091] [PMID: 26554714]
[39]
Tang, W.H.W.; Wang, Z.; Kennedy, D.J.; Wu, Y.; Buffa, J.A.; Agatisa-Boyle, B.; Li, X.S.; Levison, B.S.; Hazen, S.L. Gut microbiota-dependent Trimethylamine N-Oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ. Res., 2015, 116(3), 448-455.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.305360] [PMID: 25599331]
[40]
Kim, R.B.; Morse, B.L.; Djurdjev, O.; Tang, M.; Muirhead, N.; Barrett, B.; Holmes, D.T.; Madore, F.; Clase, C.M.; Rigatto, C.; Levin, A.; Agharazii, M.; Blouin, J.; Samson, F.; Akbarii, A.; Cheesman, J.; Courtney, J.; Hamer, S.; Delic, E.; Cronin, V.; Barré, P.; Golden, J.; Barrett, B.; Langille, E.; Adams, S.; Morgan, J.; Clase, C.; Moreau, C.; Cooper, S.; Forzley, B.; Caron, S.; Granger, S.; Valley, S.; Sather, H.; Cournoyer, S.; Menard, L.; Roy, M.; Skidmore, H.; Beaudry, D.; Dionne, J.; Chow, J.; Sahraei, V.; Donnelly, S.; Dacouris, N.; Marticorena, R.; Hemmelgarn, B.; Gulewich, S.; Hamilton, T.; Keown, P.; Zalunardo, N.; Rogers, D.; Tut, R.; Paquette, M.; Yung, R.; Levin, A.; Ferguson, N.; Tang, M.; Chiu, H.; Carlson, K.; Sioson, L.; Perry, T.; Sheriff, Z.; Rozen, N.; Lok, C.; Cross, M.; Forrester, C.; Cotoi, A.; Madore, F.; Maltais, M.; Moist, L.; Gallo, K.; Langford, S.; Slamen, L.; Cram, D.; Muirhead, N.; Edgar, M.J.; Gray, T.; Edgar, C.; Groeneweg, K.; McKinnon, E.; McRae, E.; Blackie, K.; Nathoo, B.; Lau, K.; Parmar, M.; Gelinas, S.; Leblanc, M.; Lépine, L.; Rigatto, C.; Friesen, D.; Soroka, S.; Fleet, S.; Squires, J.; Thanamayooran, S.; Binder, M.; Hines, C.; McNeil, B.; McDougall, P.; Howard, J.; Gillis, D.; Hines, K.; Tobe, S.; Chessman, M.; Perkins, N.; Agelopoulos, M.; Knox, S.; Richards, T.; Tonelli, M.; Szigety, S.; Opgenorth, D.; Yeates, K.; Mahoney, K. Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events. Kidney Int., 2016, 89(5), 1144-1152.
[http://dx.doi.org/10.1016/j.kint.2016.01.014] [PMID: 27083288]
[41]
Missailidis, C.; Hällqvist, J.; Qureshi, A.R.; Barany, P.; Heimbürger, O.; Lindholm, B.; Stenvinkel, P.; Bergman, P. Serum trimethylamine-N-oxide is strongly related to renal function and predicts outcome in chronic kidney disease. PLoS One, 2016, 11(1), e0141738.
[http://dx.doi.org/10.1371/journal.pone.0141738] [PMID: 26751065]
[42]
Stubbs, J.R.; House, J.A.; Ocque, A.J.; Zhang, S.; Johnson, C.; Kimber, C.; Schmidt, K.; Gupta, A.; Wetmore, J.B.; Nolin, T.D.; Spertus, J.A.; Yu, A.S. Serum trimethylamine- N -oxide is elevated in CKD and correlates with coronary atherosclerosis burden. J. Am. Soc. Nephrol., 2016, 27(1), 305-313.
[http://dx.doi.org/10.1681/ASN.2014111063] [PMID: 26229137]
[43]
Gruppen, E.G.; Garcia, E.; Connelly, M.A.; Jeyarajah, E.J.; Otvos, J.D.; Bakker, S.J.L.; Dullaart, R.P.F. TMAO is associated with mortality: Impact of modestly impaired renal function. Sci. Rep., 2017, 7(1), 13781.
[http://dx.doi.org/10.1038/s41598-017-13739-9] [PMID: 29061990]
[44]
Shafi, T.; Powe, N.R.; Meyer, T.W.; Hwang, S.; Hai, X.; Melamed, M.L.; Banerjee, T.; Coresh, J.; Hostetter, T.H. Trimethylamine N -oxide and cardiovascular events in hemodialysis patients. J. Am. Soc. Nephrol., 2017, 28(1), 321-331.
[http://dx.doi.org/10.1681/ASN.2016030374] [PMID: 27436853]
[45]
Xu, K.Y.; Xia, G.H.; Lu, J.Q.; Chen, M.X.; Zhen, X.; Wang, S.; You, C.; Nie, J.; Zhou, H.W.; Yin, J. Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients. Sci. Rep., 2017, 7(1), 1445.
[http://dx.doi.org/10.1038/s41598-017-01387-y] [PMID: 28469156]
[46]
Hsu, C.N.; Lu, P.C.; Lo, M.H.; Lin, I.C.; Chang-Chien, G.P.; Lin, S.; Tain, Y.L. Gut microbiota-dependent trimethylamine N-oxide pathway associated with cardiovascular risk in children with early-stage chronic kidney disease. Int. J. Mol. Sci., 2018, 19(12), 3699.
[http://dx.doi.org/10.3390/ijms19123699] [PMID: 30469463]
[47]
Stubbs, J.R.; Stedman, M.R.; Liu, S.; Long, J.; Franchetti, Y.; West, R.E., III; Prokopienko, A.J.; Mahnken, J.D.; Chertow, G.M.; Nolin, T.D. Trimethylamine N-oxide and cardiovascular outcomes in patients with ESKD receiving maintenance hemodialysis. Clin. J. Am. Soc. Nephrol., 2019, 14(2), 261-267.
[http://dx.doi.org/10.2215/CJN.06190518] [PMID: 30665924]
[48]
Guo, F.; Qiu, X.; Tan, Z.; Li, Z.; Ouyang, D. Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction. BMC Cardiovasc. Disord., 2020, 20(1), 394.
[http://dx.doi.org/10.1186/s12872-020-01669-w] [PMID: 32859154]
[49]
Hsu, C.N.; Chang, C.G.P.; Lin, S.; Hou, C.Y.; Lu, P.C.; Tain, Y.L. Association of trimethylamine, trimethylamine N-oxide, and dimethylamine with cardiovascular risk in children with chronic kidney disease. J. Clin. Med., 2020, 9(2), 336.
[http://dx.doi.org/10.3390/jcm9020336] [PMID: 31991725]
[50]
Zheng, Y.; Tang, Z.; You, L.; Wu, Y.; Liu, J.; Xue, J. Trimethylamine- N -oxide is an independent risk factor for hospitalization events in patients receiving maintenance hemodialysis. Ren. Fail., 2020, 42(1), 580-586.
[http://dx.doi.org/10.1080/0886022X.2020.1781170] [PMID: 32576072]
[51]
Yin, J.; Liao, S.X.; He, Y.; Wang, S.; Xia, G.H.; Liu, F.T.; Zhu, J.J.; You, C.; Chen, Q.; Zhou, L.; Pan, S.Y.; Zhou, H.W. Dysbiosis of Gut microbiota with reduced trimethylamine-n-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack. J. Am. Heart Assoc., 2015, 4(11), e002699.
[http://dx.doi.org/10.1161/JAHA.115.002699] [PMID: 26597155]
[52]
Haghikia, A.; Li, X.S.; Liman, T.G.; Bledau, N.; Schmidt, D.; Zimmermann, F. Kränkel, N.; Widera, C.; Sonnenschein, K.; Haghikia, A.; Weissenborn, K.; Fraccarollo, D.; Heimesaat, M.M.; Bauersachs, J.; Wang, Z.; Zhu, W.; Bavendiek, U.; Hazen, S.L.; Endres, M.; Landmesser, U. Gut microbiota–dependent trimethylamine N -oxide predicts risk of cardiovascular events in patients with stroke and is related to proinflammatory monocytes. Arterioscler. Thromb. Vasc. Biol., 2018, 38(9), 2225-2235.
[http://dx.doi.org/10.1161/ATVBAHA.118.311023] [PMID: 29976769]
[53]
Nie, J.; Xie, L.; Zhao, B.; Li, Y.; Qiu, B.; Zhu, F.; Li, G.; He, M.; Wang, Y.; Wang, B.; Liu, S.; Zhang, H.; Guo, H.; Cai, Y.; Huo, Y.; Hou, F.F.; Xu, X.; Qin, X. Serum trimethylamine N-oxide concentration is positively associated with first stroke in hypertensive patients. Stroke, 2018, 49(9), 2021-2028.
[http://dx.doi.org/10.1161/STROKEAHA.118.021997] [PMID: 30354996]
[54]
Liang, Z.; Dong, Z.; Guo, M.; Shen, Z.; Yin, D.; Hu, S.; Hai, X. Trimethylamine N-oxide as a risk marker for ischemic stroke in patients with atrial fibrillation. J. Biochem. Mol. Toxicol., 2019, 33(2), e22246.
[http://dx.doi.org/10.1002/jbt.22246] [PMID: 30370581]
[55]
Rexidamu, M.; Li, H.; Jin, H.; Huang, J. Serum levels of trimethylamine-N-oxide in patients with ischemic stroke. Biosci. Rep., 2019, 39(6), BSR20190515.
[http://dx.doi.org/10.1042/BSR20190515] [PMID: 31142624]
[56]
Zhai, Q.; Wang, X.; Chen, C.; Tang, Y.; Wang, Y.; Tian, J.; Zhao, Y.; Liu, X. Prognostic value of plasma trimethylamine N-oxide levels in patients with acute ischemic stroke. Cell. Mol. Neurobiol., 2019, 39(8), 1201-1206.
[http://dx.doi.org/10.1007/s10571-019-00714-3] [PMID: 31332666]
[57]
Hou, L.; Zhang, Y.; Zheng, D.; Shi, H.; Zou, C.; Zhang, H.; Lu, Z.; Du, H. Increasing trimethylamine N-oxide levels as a predictor of early neurological deterioration in patients with acute ischemic stroke. Neurol. Res., 2020, 42(2), 153-158.
[http://dx.doi.org/10.1080/01616412.2019.1710416] [PMID: 31928326]
[58]
Schneider, C.; Okun, J.G.; Schwarz, K.V.; Hauke, J.; Zorn, M.; Nürnberg, C.; Ungerer, M.; Ringleb, P.A.; Mundiyanapurath, S. Trimethylamine-N-oxide is elevated in the acute phase after ischaemic stroke and decreases within the first days. Eur. J. Neurol., 2020, 27(8), 1596-1603.
[http://dx.doi.org/10.1111/ene.14253] [PMID: 32282978]
[59]
Sun, T.; Zhang, Y.; Yin, J.; Peng, X.; Zhou, L.; Huang, S.; Wen, Y.; Cao, B.; Chen, L.; Li, X.; Yang, W.; Tan, A.; Cheng, J.; Liu, L. Association of gut microbiota-dependent metabolite trimethylamine N-oxide with first ischemic stroke. J. Atheroscler. Thromb., 2021, 28(4), 320-328.
[http://dx.doi.org/10.5551/jat.55962] [PMID: 32641646]
[60]
Tan, C.; Wang, H.; Gao, X.; Xu, R.; Zeng, X.; Cui, Z.; Zhu, J.; Wu, Q.; Xia, G.; Zhou, H.; He, Y.; Yin, J. Dynamic changes and prognostic value of gut microbiota-dependent trimethylamine-N-oxide in acute ischemic stroke. Front. Neurol., 2020, 11, 29.
[http://dx.doi.org/10.3389/fneur.2020.00029] [PMID: 32082246]
[61]
Wu, C.; Xue, F.; Lian, Y.; Zhang, J.; Wu, D.; Xie, N.; Chang, W.; Chen, F.; Wang, L.; Wei, W.; Yang, K.; Zhao, W.; Wu, L.; Song, H.; Ma, Q.; Ji, X. Relationship between elevated plasma trimethylamine N-oxide levels and increased stroke injury. Neurology, 2020, 94(7), e667-e677.
[http://dx.doi.org/10.1212/WNL.0000000000008862] [PMID: 31907287]
[62]
Tang, W.H.W.; Wang, Z.; Fan, Y.; Levison, B.; Hazen, J.E.; Donahue, L.M.; Wu, Y.; Hazen, S.L. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: Refining the gut hypothesis. J. Am. Coll. Cardiol., 2014, 64(18), 1908-1914.
[http://dx.doi.org/10.1016/j.jacc.2014.02.617] [PMID: 25444145]
[63]
Kaysen, G.A.; Johansen, K.L.; Chertow, G.M.; Dalrymple, L.S.; Kornak, J.; Grimes, B.; Dwyer, T.; Chassy, A.W.; Fiehn, O. Associations of trimethylamine N-oxide with nutritional and inflammatory biomarkers and cardiovascular outcomes in patients new to dialysis. J. Ren. Nutr., 2015, 25(4), 351-356.
[http://dx.doi.org/10.1053/j.jrn.2015.02.006] [PMID: 25802017]
[64]
Mente, A.; Chalcraft, K.; Ak, H.; Davis, A.D.; Lonn, E.; Miller, R.; Potter, M.A.; Yusuf, S.; Anand, S.S.; McQueen, M.J. The relationship between trimethylamine-N-oxide and prevalent cardiovascular disease in a multiethnic population living in canada. Can. J. Cardiol., 2015, 31(9), 1189-1194.
[http://dx.doi.org/10.1016/j.cjca.2015.06.016] [PMID: 26239008]
[65]
Tang, W.H.W.; Wang, Z.; Shrestha, K.; Borowski, A.G.; Wu, Y.; Troughton, R.W.; Klein, A.L.; Hazen, S.L. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J. Card. Fail., 2015, 21(2), 91-96.
[http://dx.doi.org/10.1016/j.cardfail.2014.11.006] [PMID: 25459686]
[66]
Trøseid, M.; Ueland, T.; Hov, J.R.; Svardal, A.; Gregersen, I.; Dahl, C.P.; Aakhus, S.; Gude, E.; Bjørndal, B.; Halvorsen, B.; Karlsen, T.H.; Aukrust, P.; Gullestad, L.; Berge, R.K.; Yndestad, A. Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J. Intern. Med., 2015, 277(6), 717-726.
[http://dx.doi.org/10.1111/joim.12328] [PMID: 25382824]
[67]
Fu, Q.; Zhao, M.; Wang, D.; Hu, H.; Guo, C.; Chen, W.; Li, Q.; Zheng, L.; Chen, B. Coronary plaque characterization assessed by optical coherence tomography and plasma trimethylamine-n-oxide levels in patients with coronary artery disease. Am. J. Cardiol., 2016, 118(9), 1311-1315.
[http://dx.doi.org/10.1016/j.amjcard.2016.07.071] [PMID: 27600460]
[68]
Meyer, K.A.; Benton, T.Z.; Bennett, B.; Jacobs, D.R.; Lloyd-Jones, D.M.; Gross, M.D.; Gordon-Larsen, P.; Zeisel, S.H. Abstract P025: Trimethylamine N-oxide not associated with coronary artery calcium in healthy, young adults with normal kidney function: Coronary artery risk development in young adults study, 2000-2011. Circulation, 2016, 133(Suppl. 1), 133.
[http://dx.doi.org/10.1161/circ.133.suppl_1.p025]
[69]
Meyer, K.A.; Benton, T.Z.; Bennett, B.J.; Jacobs, D.R., Jr; Lloyd, J.D.M.; Gross, M.D.; Carr, J.J.; Gordon, L.P.; Zeisel, S.H. Microbiota-dependent metabolite trimethylamine N-oxide and coronary artery calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA). J. Am. Heart Assoc., 2016, 5(10), e003970.
[http://dx.doi.org/10.1161/JAHA.116.003970] [PMID: 27792658]
[70]
Senthong, V.; Li, X.S.; Hudec, T.; Coughlin, J.; Wu, Y.; Levison, B.; Wang, Z.; Hazen, S.L.; Tang, W.H.W. Plasma trimethylamine N -Oxide, a gut microbe–generated phosphatidylcholine metabolite, is associated with atherosclerotic burden. J. Am. Coll. Cardiol., 2016, 67(22), 2620-2628.
[http://dx.doi.org/10.1016/j.jacc.2016.03.546] [PMID: 27256833]
[71]
Senthong, V.; Wang, Z.; Li, X.S.; Fan, Y.; Wu, Y.; Wilson Tang, W.H.; Hazen, S.L. Intestinal microbiota-generated metabolite trimethylamine- N- oxide and 5-year mortality risk in stable coronary artery disease: The contributory role of intestinal microbiota in a COURAGE-like patient cohort. J. Am. Heart Assoc., 2016, 5(6), e002816.
[http://dx.doi.org/10.1161/JAHA.115.002816] [PMID: 27287696]
[72]
Senthong, V.; Wang, Z.; Fan, Y.; Wu, Y.; Hazen, S.L.; Tang, W.H.W. Trimethylamine N -oxide and mortality risk in patients with peripheral artery disease. J. Am. Heart Assoc., 2016, 5(10), e004237.
[http://dx.doi.org/10.1161/JAHA.116.004237] [PMID: 27792653]
[73]
Skagen, K. Trøseid, M.; Ueland, T.; Holm, S.; Abbas, A.; Gregersen, I.; Kummen, M.; Bjerkeli, V.; Reier, N.F.; Russell, D.; Svardal, A.; Karlsen, T.H.; Aukrust, P.; Berge, R.K.; Hov, J.E.R.; Halvorsen, B.; Skjelland, M. The Carnitine-butyrobetaine-trimethylamine-N-oxide pathway and its association with cardiovascular mortality in patients with carotid atherosclerosis. Atherosclerosis, 2016, 247, 64-69.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.01.033] [PMID: 26868510]
[74]
Suzuki, T.; Heaney, LM. Trimethylamine N-oxide and prognosis in acute heart failure. Heart, 2016, 102(11), 841-848.
[75]
Suzuki, T.; Heaney, L.M.; Jones, D.J.L.; Ng, L.L. Trimethylamine N-oxide and risk stratification after acute myocardial infarction. Clin. Chem., 2017, 63(1), 420-428.
[http://dx.doi.org/10.1373/clinchem.2016.264853] [PMID: 28062632]
[76]
Borisovich, M.A.; Aleksandrovna, I.S.; Mikhailovna, L.Y.; Gennadievna, T.L.; Akylbekovna, T.A.; Moraru, D. Relationship between trimethylamine n-oxide and total cardiovascular risk in the population of central Kazakhstan. Acta Med. Mediter., 2018, 34(1), 59-63.
[77]
Li, X.S.; Wang, Z.; Cajka, T.; Buffa, J.A.; Nemet, I.; Hurd, A.G.; Gu, X.; Skye, S.M.; Roberts, A.B.; Wu, Y.; Li, L.; Shahen, C.J.; Wagner, M.A.; Hartiala, J.A.; Kerby, R.L.; Romano, K.A.; Han, Y.; Obeid, S.; Lüscher, T.F.; Allayee, H.; Rey, F.E.; DiDonato, J.A.; Fiehn, O.; Tang, W.H.W.; Hazen, S.L. Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight, 2018, 3(6), e99096.
[http://dx.doi.org/10.1172/jci.insight.99096] [PMID: 29563342]
[78]
Liu, X.; Xie, Z.; Sun, M.; Wang, X.; Li, J.; Cui, J.; Zhang, F.; Yin, L.; Huang, D.; Hou, J.; Tian, J.; Yu, B. Plasma trimethylamine N-oxide is associated with vulnerable plaque characteristics in CAD patients as assessed by optical coherence tomography. Int. J. Cardiol., 2018, 265, 18-23.
[http://dx.doi.org/10.1016/j.ijcard.2018.04.126] [PMID: 29729869]
[79]
Svingen, G.F.T.; Zuo, H.; Ueland, P.M.; Seifert, R.; Løland, K.H.; Pedersen, E.R.; Schuster, P.M.; Karlsson, T.; Tell, G.S.; Schartum, H.H.; Olset, H.; Svenningsson, M.; Strand, E.; Nilsen, D.W.; Nordrehaug, J.E.; Dhar, I.; Nygård, O. Increased plasma trimethylamine- N -oxide is associated with incident atrial fibrillation. Int. J. Cardiol., 2018, 267, 100-106.
[http://dx.doi.org/10.1016/j.ijcard.2018.04.128] [PMID: 29957250]
[80]
Chou, R.H.; Chen, C.Y.; Chen, I.C.; Huang, H.L.; Lu, Y.W.; Kuo, C.S.; Chang, C.C.; Huang, P.H.; Chen, J.W.; Lin, S.J. Trimethylamine N-oxide, circulating endothelial progenitor cells, and endothelial function in patients with stable angina. Sci. Rep., 2019, 9(1), 4249.
[http://dx.doi.org/10.1038/s41598-019-40638-y] [PMID: 30862856]
[81]
Gong, D.; Zhang, L.; Zhang, Y.; Wang, F.; Zhao, Z.; Zhou, X. Gut microbial metabolite trimethylamine N-oxide is related to thrombus formation in atrial fibrillation patients. Am. J. Med. Sci., 2019, 358(6), 422-428.
[http://dx.doi.org/10.1016/j.amjms.2019.09.002] [PMID: 31666184]
[82]
Kaburova, A.N.; Poyarkov, S.V.; Makarov, V.V.; Drapkina, O.M.; Uydin, S.M.; Pokrovskaya, M.S.; Koretsky, S.N.; Efimova, I.A.; Matskevich, L.A.; Gomiranova, N.V. 219Serum trimethylamine Noxide levels and 16S rRNA gut microbiota profiling in patients with heart failure and preserved ejection fraction and healthy individuals. Eur. Heart J., 2019, 40(Suppl. 1), ehz747.0060.
[http://dx.doi.org/10.1093/eurheartj/ehz747.0060]
[83]
Matsuzawa, Y.; Nakahashi, H.; Konishi, M.; Sato, R.; Kawashima, C.; Kikuchi, S.; Akiyama, E.; Iwahashi, N.; Maejima, N.; Okada, K.; Ebina, T.; Hibi, K.; Kosuge, M.; Ishigami, T.; Tamura, K.; Kimura, K. Microbiota-derived trimethylamine N-oxide predicts cardiovascular risk after STEMI. Sci. Rep., 2019, 9(1), 11647.
[http://dx.doi.org/10.1038/s41598-019-48246-6] [PMID: 31406181]
[84]
Reiner, M.F.; Müller, D.; Gobbato, S.; Stalder, O.; Limacher, A.; Bonetti, N.R.; Pasterk, L.; Méan, M.; Rodondi, N.; Aujesky, D.; Angelillo-Scherrer, A.; Matter, C.M.; Lüscher, T.F.; Camici, G.G.; von Eckardstein, A.; Beer, J.H. Gut microbiota-dependent Trimethylamine-N-Oxide (TMAO) shows a U-shaped association with mortality but not with recurrent venous thromboembolism. Thromb. Res., 2019, 174, 40-47.
[http://dx.doi.org/10.1016/j.thromres.2018.12.011] [PMID: 30553164]
[85]
Roncal, C.; Martínez, A.E.; Orbe, J.; Ravassa, S.; Fernandez, M.A.; Saenz, P.G.; Ugarte, A.; De Mendoza, E.H.A.; Rodriguez, J.A.; Fernández, A.S.; Fernández, A.L.; Oyarzabal, J.; Paramo, J.A. Trimethylamine-N-Oxide (TMAO) predicts cardiovascular mortality in peripheral artery disease. Sci. Rep., 2019, 9(1), 15580.
[http://dx.doi.org/10.1038/s41598-019-52082-z] [PMID: 31666590]
[86]
Sheng, Z.; Tan, Y.; Liu, C.; Zhou, P.; Li, J.; Zhou, J.; Chen, R.; Chen, Y.; Song, L.; Zhao, H.; Yan, H. Relation of circulating trimethylamine N-oxide with coronary atherosclerotic burden in patients With ST-segment elevation myocardial infarction. Am. J. Cardiol., 2019, 123(6), 894-898.
[http://dx.doi.org/10.1016/j.amjcard.2018.12.018] [PMID: 30594289]
[87]
Tan, Y.; Sheng, Z.; Zhou, P.; Liu, C.; Zhao, H.; Song, L.; Li, J.; Zhou, J.; Chen, Y.; Wang, L.; Qian, H.; Sun, Z.; Qiao, S.; Xu, B.; Gao, R.; Yan, H. Plasma trimethylamine N-oxide as a novel biomarker for plaque rupture in patients with ST-segment–elevation myocardial infarction. Circ. Cardiovasc. Interv., 2019, 12(1), e007281.
[http://dx.doi.org/10.1161/CIRCINTERVENTIONS.118.007281] [PMID: 30599768]
[88]
Yu, D.; Shu, X.O.; Rivera, E.S.; Zhang, X.; Cai, Q.; Calcutt, M.W.; Xiang, Y.B.; Li, H.; Gao, Y.T.; Wang, T.J.; Zheng, W. Urinary levels of trimethylamine-N-oxide and incident coronary heart disease: A prospective investigation among urban Chinese adults. J. Am. Heart Assoc., 2019, 8(1), e010606.
[http://dx.doi.org/10.1161/JAHA.118.010606] [PMID: 30606084]
[89]
Zheng, L.; Zheng, J.; Xie, Y.; Li, Z.; Guo, X.; Sun, G.; Sun, Z.; Xing, F.; Sun, Y. Serum gut microbe-dependent trimethylamine N-oxide improves the prediction of future cardiovascular disease in a community-based general population. Atherosclerosis, 2019, 280, 126-131.
[http://dx.doi.org/10.1016/j.atherosclerosis.2018.11.010] [PMID: 30508691]
[90]
Bin Waleed, K.; Lu, Y.; Liu, Q.; Zeng, F.; Tu, H.; Wei, Y.; Xu, S.; Zhang, Z.; Rongfeng, Y.; Fan, A.; Altaf, A.; Chang, J.; Wang, L. Association of trimethylamine N-oxide with coronary atherosclerotic burden in patients with non-ST-segment elevation myocardial infarction. Medicine, 2020, 99(27), e20794.
[http://dx.doi.org/10.1097/MD.0000000000020794] [PMID: 32629663]
[91]
Büttner, P.; Okun, J.G.; Hauke, J.; Holzwirth, E.; Obradovic, D.; Hindricks, G.; Thiele, H.; Kornej, J. Trimethylamine N-oxide in atrial fibrillation progression. Int. J. Cardiol. Heart Vasc., 2020, 29, 100554.
[http://dx.doi.org/10.1016/j.ijcha.2020.100554] [PMID: 32885030]
[92]
Dong, Z.X.; Zhang, J.; Luo, Y.C.; Zhao, M.M.; Cai, J.G.; Cheng, S.; Zheng, L.M.; Hai, X. The correlation between trimethylamine N-oxide, lipoprotein ratios, and conventional lipid parameters in patients with unstable angina pectoris. Biosci. Rep., 2020, 40(1), BSR20192657.
[http://dx.doi.org/10.1042/BSR20192657] [PMID: 31894847]
[93]
Guo, F.; Zhou, J.; Li, Z.; Yu, Z.; Ouyang, D. The association between trimethylamine n-oxide and its predecessors choline, l-carnitine, and betaine with coronary artery disease and artery stenosis. Cardiol. Res. Pract., 2020, 2020, 1-10.
[http://dx.doi.org/10.1155/2020/5854919] [PMID: 32855821]
[94]
Heianza, Y.; Ma, W.; DiDonato, J.A.; Sun, Q.; Rimm, E.B.; Hu, F.B.; Rexrode, K.M.; Manson, J.E.; Qi, L. Long-term changes in gut microbial metabolite trimethylamine N-oxide and coronary heart disease risk. J. Am. Coll. Cardiol., 2020, 75(7), 763-772.
[http://dx.doi.org/10.1016/j.jacc.2019.11.060] [PMID: 32081286]
[95]
Hochstrasser, S.R.; Metzger, K.; Vincent, A.M.; Becker, C.; Keller, A.K.J.; Beck, K.; Perrig, S.; Tisljar, K.; Sutter, R.; Schuetz, P.; Bernasconi, L.; Neyer, P.; Marsch, S.; Hunziker, S. Trimethylamine-N-Oxide (TMAO) predicts short- and long-term mortality and poor neurological outcome in out-of-hospital cardiac arrest patients. Clin. Chem. Lab. Med., 2021, 59(2), 393-402.
[http://dx.doi.org/10.1515/cclm-2020-0159] [PMID: 32866111]
[96]
Tan, Y.; Zhou, J.; Liu, C.; Zhou, P.; Sheng, Z.; Li, J.; Chen, R.; Song, L.; Zhao, H.; Xu, B.; Gao, R.; Yan, H. Association between plasma trimethylamine N-oxide and neoatherosclerosis in patients with very late stent thrombosis. Can. J. Cardiol., 2020, 36(8), 1252-1260.
[http://dx.doi.org/10.1016/j.cjca.2019.10.041] [PMID: 32595007]
[97]
Yazaki, Y.; Aizawa, K.; Israr, M.Z.; Negishi, K.; Salzano, A.; Saitoh, Y.; Kimura, N.; Kono, K.; Heaney, L.; Cassambai, S.; Bernieh, D.; Lai, F.; Imai, Y.; Kario, K.; Nagai, R.; Ng, L.L.; Suzuki, T. Ethnic differences in association of outcomes with trimethylamine N-oxide in acute heart failure patients. ESC Heart Fail., 2020, 7(5), 2373-2378.
[http://dx.doi.org/10.1002/ehf2.12777] [PMID: 32598563]
[98]
Zhou, X.; Jin, M.; Liu, L.; Yu, Z.; Lu, X.; Zhang, H. Trimethylamine N-oxide and cardiovascular outcomes in patients with chronic heart failure after myocardial infarction. ESC Heart Fail., 2020, 7(1), 189-194.
[http://dx.doi.org/10.1002/ehf2.12552] [PMID: 31960610]
[99]
Zuo, K.; Liu, X.; Wang, P.; Jiao, J.; Han, C.; Liu, Z.; Yin, X.; Li, J.; Yang, X. Metagenomic data-mining reveals enrichment of trimethylamine-N-oxide synthesis in gut microbiome in atrial fibrillation patients. BMC Genomics, 2020, 21(1), 526.
[http://dx.doi.org/10.1186/s12864-020-06944-w] [PMID: 32731896]
[100]
Li, J.; Sheng, Z.; Tan, Y.; Zhou, P.; Liu, C.; Zhao, H.; Song, L.; Zhou, J.; Chen, R.; Chen, Y.; Yan, H. Association of plasma trimethylamine N-Oxide level with healed culprit plaques examined by optical coherence tomography in patients with ST-Segment elevation myocardial infarction. Nutr. Metab. Cardiovasc. Dis., 2021, 31(1), 145-152.
[http://dx.doi.org/10.1016/j.numecd.2020.06.016] [PMID: 33500103]
[101]
Wilson, A.; Teft, W.A.; Morse, B.L.; Choi, Y.H.; Woolsey, S.; DeGorter, M.K.; Hegele, R.A.; Tirona, R.G.; Kim, R.B. Trimethylamine-N-oxide: A novel biomarker for the identification of inflammatory bowel disease. Dig. Dis. Sci., 2015, 60(12), 3620-3630.
[http://dx.doi.org/10.1007/s10620-015-3797-3] [PMID: 26160437]
[102]
Kummen, M.; Vesterhus, M. Trøseid, M.; Moum, B.; Svardal, A.; Boberg, K.M.; Aukrust, P.; Karlsen, T.H.; Berge, R.K.; Hov, J.R. Elevated Trimethylamine- N -Oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients with normal liver function. United Eur. Gastroenterol. J.,, 2017, 5(4), 532-541.
[http://dx.doi.org/10.1177/2050640616663453] [PMID: 28588885]
[103]
Liu, X.; Liu, H.; Yuan, C.; Zhang, Y.; Wang, W.; Hu, S.; Liu, L.; Wang, Y. Preoperative serum TMAO level is a new prognostic marker for colorectal cancer. Biomarkers Med., 2017, 11(5), 443-447.
[http://dx.doi.org/10.2217/bmm-2016-0262] [PMID: 28621609]
[104]
Barrea, L.; Annunziata, G.; Muscogiuri, G.; Di Somma, C.; Laudisio, D.; Maisto, M.; De Alteriis, G.; Tenore, G.; Colao, A.; Savastano, S. Trimethylamine-N-Oxide (TMAO) as novel potential biomarker of early predictors of metabolic syndrome. Nutrients, 2018, 10(12), 1971.
[http://dx.doi.org/10.3390/nu10121971] [PMID: 30551613]
[105]
Liu, Z.Y.; Tan, X.Y.; Li, Q.J.; Liao, G.C.; Fang, A.P.; Zhang, D.M.; Chen, P.Y.; Wang, X.Y.; Luo, Y.; Long, J.A.; Zhong, R.H.; Zhu, H.L. Trimethylamine N-oxide, a gut microbiota-dependent metabolite of choline, is positively associated with the risk of primary liver cancer: A case-control study. Nutr. Metab., 2018, 15(1), 81.
[http://dx.doi.org/10.1186/s12986-018-0319-2] [PMID: 30479648]
[106]
Ottiger, M.; Nickler, M.; Steuer, C.; Bernasconi, L.; Huber, A.; Christ, C.M.; Henzen, C.; Hoess, C.; Thomann, R.; Zimmerli, W.; Mueller, B.; Schuetz, P. Gut, microbiota-dependent trimethylamine- N -oxide is associated with long-term all-cause mortality in patients with exacerbated chronic obstructive pulmonary disease. Nutrition, 2018, 45, 135-141.e1.
[http://dx.doi.org/10.1016/j.nut.2017.07.001] [PMID: 28870405]
[107]
Vogt, N.M.; Romano, K.A.; Darst, B.F.; Engelman, C.D.; Johnson, S.C.; Carlsson, C.M.; Asthana, S.; Blennow, K.; Zetterberg, H.; Bendlin, B.B.; Rey, F.E. The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alzheimers Res. Ther., 2018, 10(1), 124.
[http://dx.doi.org/10.1186/s13195-018-0451-2] [PMID: 30579367]
[108]
Coras, R.; Kavanaugh, A.; Boyd, T.; Huynh, D.; Lagerborg, K.A.; Xu, Y.J.; Rosenthal, S.B.; Jain, M.; Guma, M. Choline metabolite, Trimethylamine N-Oxide (TMAO), is associated with inflammation in psoriatic arthritis. Clin. Exp. Rheumatol., 2019, 37(3), 481-484.
[PMID: 30620278]
[109]
Gao, X.; Tian, Y.; Randell, E.; Zhou, H.; Sun, G. Unfavorable associations between serum trimethylamine N-oxide and L-carnitine levels with components of metabolic syndrome in the newfoundland population. Front. Endocrinol. (Lausanne), 2019, 10, 168.
[http://dx.doi.org/10.3389/fendo.2019.00168] [PMID: 30972022]
[110]
Tan, X.; Liu, Y.; Long, J.; Chen, S.; Liao, G.; Wu, S.; Li, C.; Wang, L.; Ling, W.; Zhu, H. Trimethylamine N -oxide aggravates liver steatosis through modulation of bile acid metabolism and inhibition of farnesoid X receptor signaling in nonalcoholic fatty liver disease. Mol. Nutr. Food Res., 2019, 63(17), 1900257.
[http://dx.doi.org/10.1002/mnfr.201900257] [PMID: 31095863]
[111]
Wen, Y.; Peng, L.; Xu, R.; Zang, N.; Huang, Q.; Zhong, M. Maternal serum trimethylamine-N-oxide is significantly increased in cases with established preeclampsia. Pregnancy Hypertens., 2019, 15, 114-117.
[http://dx.doi.org/10.1016/j.preghy.2018.12.001] [PMID: 30825906]
[112]
Huang, J.; Liu, L.; Chen, C.; Gao, Y. PCOS without hyperandrogenism is associated with higher plasma trimethylamine N-oxide levels. BMC Endocr. Disord., 2020, 20(1), 3.
[http://dx.doi.org/10.1186/s12902-019-0486-9] [PMID: 31906930]
[113]
Huang, X.; Li, Z.; Gao, Z.; Wang, D.; Li, X.; Li, Y.; Mi, C.; Lei, J. Association between risk of preeclampsia and maternal plasma trimethylamine-N-oxide in second trimester and at the time of delivery. BMC Pregnancy Childbirth, 2020, 20(1), 302.
[http://dx.doi.org/10.1186/s12884-020-02997-7] [PMID: 32429856]
[114]
León, M.P.; Villamil, R.H.; Li, X.S.; Shih, D.M.; Hui, S.T.; Ocampo, M.E.; López, C.B.; Morán, R.S.; Olivares, A.M.; Grandini, R.P.; Macías, K.L.; González, G.I.;Hernández, P.R.; Gómez, P.F.; Campos, P.F.; Aguilar, S.C.; Larrieta, C.E.; Villarreal, M.T.; Wang, Z.; Lusis, A.J.; Hazen, S.L.; Huertas, V.A.; Canizales, Q.S. Trimethylamine N-oxide levels are associated with NASH in obese subjects with type 2 diabetes. Diabetes Metab., 2021, 47(2), 101183.
[http://dx.doi.org/10.1016/j.diabet.2020.07.010] [PMID: 32791310]
[115]
Liu, Y.; Guo, Y.L.; Meng, S.; Gao, H.; Sui, L.J.; Jin, S.; Li, Y.; Fan, S.G. Gut microbiota–dependent Trimethylamine N-oxide are related with hip fracture in postmenopausal women: A matched case-control study. Aging (Albany NY), 2020, 12(11), 10633-10641.
[http://dx.doi.org/10.18632/aging.103283] [PMID: 32482913]
[116]
Quan, L.; Yi, J.; Zhao, Y.; Zhang, F.; Shi, X.T.; Feng, Z.; Miller, H.L. Plasma trimethylamine N-oxide, a gut microbe–generated phosphatidylcholine metabolite, is associated with autism spectrum disorders. Neurotoxicology, 2020, 76, 93-98.
[http://dx.doi.org/10.1016/j.neuro.2019.10.012] [PMID: 31704102]
[117]
Zhai, Q.; Sun, T.; Sun, C.; Yan, L.; Wang, X.; Wang, Y. High plasma levels of trimethylamine N-oxide are associated with poor outcome in intracerebral hemorrhage patients. Neurol. Sci., 2020, 42(3), 1009-1016.
[118]
Zhu, C.; Li, G.; Lv, Z.; Li, J.; Wang, X. Kang, J Association of plasma trimethylamine-N-oxide levels with post-stroke cognitive impairment: A 1-year longitudinal study. Neurological sciences, 2020, 41(1), 57-63.
[119]
Oellgaard, J.; Winther, S.A.; Hansen, T.S.; Rossing, P.; von Scholten, B.J. Trimethylamine N-oxide (TMAO) as a new potential therapeutic target for insulin resistance and cancer. Curr. Pharm. Des., 2017, 23(25), 3699-3712.
[PMID: 28641532]
[120]
Motika, M.S.; Zhang, J.; Cashman, J.R. Flavin-containing monooxygenase 3 and human disease. Expert Opin. Drug Metab. Toxicol., 2007, 3(6), 831-845.
[http://dx.doi.org/10.1517/17425255.3.6.831] [PMID: 18028028]
[121]
Koeth, R.A.; Wang, Z.; Levison, B.S.; Buffa, J.A.; Org, E.; Sheehy, B.T.; Britt, E.B.; Fu, X.; Wu, Y.; Li, L.; Smith, J.D.; DiDonato, J.A.; Chen, J.; Li, H.; Wu, G.D.; Lewis, J.D.; Warrier, M.; Brown, J.M.; Krauss, R.M.; Tang, W.H.W.; Bushman, F.D.; Lusis, A.J.; Hazen, S.L. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med., 2013, 19(5), 576-585.
[http://dx.doi.org/10.1038/nm.3145] [PMID: 23563705]
[122]
Mingrone, G.; Greco, A.V.; Capristo, E.; Benedetti, G.; Giancaterini, A.; Gaetano, A.D.; Gasbarrini, G. L-carnitine improves glucose disposal in type 2 diabetic patients. J. Am. Coll. Nutr., 1999, 18(1), 77-82.
[http://dx.doi.org/10.1080/07315724.1999.10718830] [PMID: 10067662]
[123]
Wang, Z.Y.; Liu, Y.Y.; Liu, G.H.; Lu, H.B.; Mao, C.Y. l -Carnitine and heart disease. Life Sci., 2018, 194, 88-97.
[http://dx.doi.org/10.1016/j.lfs.2017.12.015] [PMID: 29241711]
[124]
Marjani, A.; Rafeeinia, A.; Tabandeh, A.; Khajeniazi, S. Metabolic syndrome in preeclampsia women in gorgan. Open Biochem. J., 2014, 8(1), 94-99.
[http://dx.doi.org/10.2174/1874091X01408010094] [PMID: 25553139]
[125]
Geng, J.; Yang, C.; Wang, B.; Zhang, X.; Hu, T.; Gu, Y.; Li, J. Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway. Biomed. Pharmacother., 2018, 97, 941-947.
[http://dx.doi.org/10.1016/j.biopha.2017.11.016] [PMID: 29136772]
[126]
Wang, Z.; Zhao, Y. Gut microbiota derived metabolites in cardiovascular health and disease. Protein Cell, 2018, 9(5), 416-431.
[http://dx.doi.org/10.1007/s13238-018-0549-0] [PMID: 29725935]
[127]
Zhu, W.; Gregory, J.C.; Org, E.; Buffa, J.A.; Gupta, N.; Wang, Z.; Li, L.; Fu, X.; Wu, Y.; Mehrabian, M.; Sartor, R.B.; McIntyre, T.M.; Silverstein, R.L.; Tang, W.H.W.; DiDonato, J.A.; Brown, J.M.; Lusis, A.J.; Hazen, S.L. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell, 2016, 165(1), 111-124.
[http://dx.doi.org/10.1016/j.cell.2016.02.011] [PMID: 26972052]
[128]
Warrier, M.; Shih, D.M.; Burrows, A.C.; Ferguson, D.; Gromovsky, A.D.; Brown, A.L.; Marshall, S.; McDaniel, A.; Schugar, R.C.; Wang, Z.; Sacks, J.; Rong, X.; Vallim, T.A.; Chou, J.; Ivanova, P.T.; Myers, D.S.; Brown, H.A.; Lee, R.G.; Crooke, R.M.; Graham, M.J.; Liu, X.; Parini, P.; Tontonoz, P.; Lusis, A.J.; Hazen, S.L.; Temel, R.E.; Brown, J.M. The TMAO-generating enzyme flavin monooxygenase 3 is a central regulator of cholesterol balance. Cell Rep., 2015, 10(3), 326-338.
[http://dx.doi.org/10.1016/j.celrep.2014.12.036] [PMID: 25600868]
[129]
Heianza, Y.; Sun, D.; Li, X.; DiDonato, J.A.; Bray, G.A.; Sacks, F.M.; Qi, L. Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: The POUNDS Lost trial. Gut, 2019, 68(2), 263-270.
[http://dx.doi.org/10.1136/gutjnl-2018-316155] [PMID: 29860242]
[130]
Miao, J.; Ling, A.V.; Manthena, P.V.; Gearing, M.E.; Graham, M.J.; Crooke, R.M.; Croce, K.J.; Esquejo, R.M.; Clish, C.B.; Vicent, D.; Biddinger, S.B. Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis. Nat. Commun., 2015, 6(1), 6498.
[http://dx.doi.org/10.1038/ncomms7498] [PMID: 25849138]
[131]
Shih, D.M.; Wang, Z.; Lee, R.; Meng, Y.; Che, N.; Charugundla, S.; Qi, H.; Wu, J.; Pan, C.; Brown, J.M.; Vallim, T.; Bennett, B.J.; Graham, M.; Hazen, S.L.; Lusis, A.J. Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis. J. Lipid Res., 2015, 56(1), 22-37.
[http://dx.doi.org/10.1194/jlr.M051680] [PMID: 25378658]
[132]
Zeng, Y.; Guo, M.; Fang, X.; Teng, F.; Tan, X.; Li, X.; Wang, M.; Long, Y.; Xu, Y. Gut microbiota-derived trimethylamine N-oxide and kidney function: A systematic review and meta-analysis. Adv. Nutr., 2021, 12(4), 1286-1304.
[http://dx.doi.org/10.1093/advances/nmab010] [PMID: 33751019]
[133]
Ufnal, M.; Zadlo, A.; Ostaszewski, R. TMAO: A small molecule of great expectations. Nutrition, 2015, 31(11-12), 1317-1323.
[http://dx.doi.org/10.1016/j.nut.2015.05.006] [PMID: 26283574]
[134]
Lombardo, M.; Aulisa, G.; Marcon, D.; Rizzo, G.; Tarsisano, M.G.; Di Renzo, L.; Federici, M.; Caprio, M.; De Lorenzo, A. Association of urinary and plasma levels of Trimethylamine N-Oxide (TMAO) with foods. Nutrients, 2021, 13(5), 1426.
[http://dx.doi.org/10.3390/nu13051426] [PMID: 33922680]
[135]
Nowiński, A.; Ufnal, M. Trimethylamine N -oxide: A harmful, protective or diagnostic marker in lifestyle diseases? Nutrition, 2018, 46, 7-12.
[http://dx.doi.org/10.1016/j.nut.2017.08.001] [PMID: 29290360]
[136]
Meyers, L.D.; Hellwig, J.P.; Otten, J.J. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements; National Academies Press: Washington, DC, 2006.
[137]
Flint, H.J.; Duncan, S.H.; Scott, K.P.; Louis, P. Links between diet, gut microbiota composition and gut metabolism. Proc. Nutr. Soc., 2015, 74(1), 13-22.
[http://dx.doi.org/10.1017/S0029665114001463] [PMID: 25268552]
[138]
Graf, D.; Di Cagno, R. Fåk, F.; Flint, H.J.; Nyman, M.; Saarela, M.; Watzl, B. Contribution of diet to the composition of the human gut microbiota. Microb. Ecol. Health Dis., 2015, 26(1), 26164.
[PMID: 25656825]
[139]
Shi, Z. Gut microbiota: An important link between western diet and chronic diseases. Nutrients, 2019, 11(10), 2287.
[http://dx.doi.org/10.3390/nu11102287] [PMID: 31554269]
[140]
Chen, K.; Zheng, X.; Feng, M.; Li, D.; Zhang, H. Gut microbiota-dependent metabolite trimethylamine N-oxide contributes to cardiac dysfunction in western diet-induced obese mice. Front. Physiol., 2017, 8, 139.
[http://dx.doi.org/10.3389/fphys.2017.00139] [PMID: 28377725]
[141]
De Filippis, F.; Pellegrini, N.; Vannini, L.; Jeffery, I.B.; La Storia, A.; Laghi, L.; Serrazanetti, D.I.; Di Cagno, R.; Ferrocino, I.; Lazzi, C.; Turroni, S.; Cocolin, L.; Brigidi, P.; Neviani, E.; Gobbetti, M.; O’Toole, P.W.; Ercolini, D. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut, 2016, 65(11), 1812-1821.
[http://dx.doi.org/10.1136/gutjnl-2015-309957] [PMID: 26416813]
[142]
Del Chierico, F.; Vernocchi, P.; Dallapiccola, B.; Putignani, L. Mediterranean diet and health: Food effects on gut microbiota and disease control. Int. J. Mol. Sci., 2014, 15(7), 11678-11699.
[http://dx.doi.org/10.3390/ijms150711678] [PMID: 24987952]
[143]
Kashyap, P.C.; Chia, N.; Nelson, H.; Segal, E.; Elinav, E. Eds.: Microbiome at the Frontier of Personalized Medicine. Mayo Clinic Proceedings; Elsevier: Amsterdam, Netherlands, 2017.
[144]
Ejtahed, H.S.; Hasani, R.S.; Larijani, B. Human microbiome as an approach to personalized medicine. Altern. Ther. Health Med., 2017, 23(6), 8-9.
[PMID: 28987073]
[145]
Dehghan, P.; Farhangi, M.A.; Nikniaz, L.; Nikniaz, Z.; Asghari, J.M. Gut microbiota-derived metabolite Trimethylamine N-Oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose-response meta- analysis. Obes. Rev., 2020, 21(5), e12993.
[http://dx.doi.org/10.1111/obr.12993] [PMID: 32017391]
[146]
Ejtahed, H.S.; Angoorani, P.; Soroush, A.R.; Hasani-Ranjbar, S.; Siadat, S.D.; Larijani, B. Gut microbiota-derived metabolites in obesity: A systematic review. Biosci. Microbiota Food Health, 2020, 39(3), 65-76.
[http://dx.doi.org/10.12938/bmfh.2019-026] [PMID: 32775123]
[147]
Farhangi, M.A.; Vajdi, M. Novel findings of the association between gut microbiota–derived metabolite trimethylamine N- oxide and inflammation: Results from a systematic review and dose-response meta-analysis. Crit. Rev. Food Sci. Nutr., 2020, 60(16), 2801-2823.
[http://dx.doi.org/10.1080/10408398.2020.1770199] [PMID: 32462890]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy