Login Register Cart 0
Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Signal Pathways and Intestinal Flora through Trimethylamine N-oxide in Alzheimer's Disease

Author(s): Yao Zhang and Wenxuan Jian*

Volume 24, Issue 9, 2023

Published on: 24 July, 2023

Page: [721 - 736] Pages: 16

DOI: 10.2174/1389203724666230717125406

Price: $65

Abstract

The current studies show signs of progress in treating Alzheimer's disease (AD) with the “brain-gut axis.” Restoring intestinal flora balance can alleviate neurodegeneration in the central nervous system. However, due to the complex mechanisms involved in the brain-gut axis, the neuroprotective mechanism brought by intestinal flora has not been fully understood. Trimethylamine N-oxide (TMAO) is a microbiota-dependent metabolism production; TMAO has been proven to be a major risk factor for atherosclerosis, thrombosis, type II diabetes, and other diseases. Meanwhile, all the above diseases are associated with AD; thus, we speculate that TMAO and AD are also correlated. Microbiota, such as Firmicutes, Ruminococcaceae, Escherichia coli, Bifidobacterium, Akkermansia, etc., correlate with the production process of TMAO. High choline intake and insulin resistance have also been identified as contributors to TMAO synthesis. With the increasing TMAO in plasma, TMAO can enter the central nervous system, causing neuroinflammation and immune responses and damaging the blood-brain barrier. TMAO can increase the expression of Aβ and the hyperphosphorylation of tau protein, regulate the signal pathways of NLRP3/ASC/caspase1, SIRT1/p53/p21/Rb, PERK/eIF2α/ER-stress, SIRT3-SOD2-mtROS, TXNIP-NLPR3, and PERK/Akt/mTOR, and stimulate the inflammation, apoptosis, endoplasmic reticulum stress, and the ROS. In this mini-review, we have summarized the diseases induced by TMAO through clinical and signal pathways, and intestinal flora correlated with TMAO. Through the analysis of diseases and mechanisms involved in TMAO, we have concluded TMAO to be a potentially important pathological factor of AD.

Keywords: Blood-brain barrier, immunity, inflammation, insulin resistance, metabolites, neurodegeneration, ROS.

« Previous Next »
Graphical Abstract

[1]
Lane, C.A.; Hardy, J.; Schott, J.M. Alzheimer’s disease. Eur. J. Neurol., 2018, 25(1), 59-70.
[http://dx.doi.org/10.1111/ene.13439] [PMID: 28872215]
[2]
Gulisano, W.; Maugeri, D.; Baltrons, M.A.; Fà, M.; Amato, A.; Palmeri, A.; D’Adamio, L.; Grassi, C.; Devanand, D.P.; Honig, L.S.; Puzzo, D.; Arancio, O. Role of amyloid-β and tau proteins in Alzheimer’s Disease: Confuting the amyloid cascade. J. Alzheimers Dis., 2018, 64(s1), S611-S631.
[http://dx.doi.org/10.3233/JAD-179935] [PMID: 29865055]
[3]
Ozben, T.; Ozben, S. Neuro-inflammation and anti-inflammatory treatment options for Alzheimer’s disease. Clin. Biochem., 2019, (72), 87-89.
[http://dx.doi.org/10.1016/j.clinbiochem.2019.04.001.] [PMID: 30954437]
[4]
Sweeney, M.D.; Sagare, A.P.; Zlokovic, B.V. Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol., 2018, 14(3), 133-150.
[http://dx.doi.org/10.1038/nrneurol.2017.188] [PMID: 29377008]
[5]
Stakos, D.A.; Stamatelopoulos, K.; Bampatsias, D.; Sachse, M.; Zormpas, E.; Vlachogiannis, N.I.; Tual-Chalot, S.; Stellos, K. The Alzheimer’s Disease amyloid-beta hypothesis in cardiovascular aging and disease. J. Am. Coll. Cardiol., 2020, 75(8), 952-967.
[http://dx.doi.org/10.1016/j.jacc.2019.12.033] [PMID: 32130931]
[6]
Tumminia, A.; Vinciguerra, F.; Parisi, M.; Frittitta, L. Type 2 diabetes mellitus and Alzheimer’s Disease: Role of insulin signalling and therapeutic implications. Int. J. Mol. Sci., 2018, 19(11), 3306.
[http://dx.doi.org/10.3390/ijms19113306] [PMID: 30355995]
[7]
Howard, R.; McShane, R.; Lindesay, J.; Ritchie, C.; Baldwin, A.; Barber, R.; Burns, A.; Dening, T.; Findlay, D.; Holmes, C.; Jones, R.; Jones, R.; McKeith, I.; Macharouthu, A.; O’Brien, J.; Sheehan, B.; Juszczak, E.; Katona, C.; Hills, R.; Knapp, M.; Ballard, C.; Brown, R.G.; Banerjee, S.; Adams, J.; Johnson, T.; Bentham, P.; Phillips, P.P.J. Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease (DOMINO-AD) trial: Secondary and post-hoc analyses. Lancet Neurol., 2015, 14(12), 1171-1181.
[http://dx.doi.org/10.1016/S1474-4422(15)00258-6] [PMID: 26515660]
[8]
Salloway, S.; Sperling, R.; Fox, N.C.; Blennow, K.; Klunk, W.; Raskind, M.; Sabbagh, M.; Honig, L.S.; Porsteinsson, A.P.; Ferris, S.; Reichert, M.; Ketter, N.; Nejadnik, B.; Guenzler, V.; Miloslavsky, M.; Wang, D.; Lu, Y.; Lull, J.; Tudor, I.C.; Liu, E.; Grundman, M.; Yuen, E.; Black, R.; Brashear, H.R. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N. Engl. J. Med., 2014, 370(4), 322-333.
[http://dx.doi.org/10.1056/NEJMoa1304839] [PMID: 24450891]
[9]
Doody, R.S.; Thomas, R.G.; Farlow, M.; Iwatsubo, T.; Vellas, B.; Joffe, S.; Kieburtz, K.; Raman, R.; Sun, X.; Aisen, P.S.; Siemers, E.; Liu-Seifert, H.; Mohs, R. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N. Engl. J. Med., 2014, 370(4), 311-321.
[http://dx.doi.org/10.1056/NEJMoa1312889] [PMID: 24450890]
[10]
Salloway, S.; Honigberg, L.A.; Cho, W.; Ward, M.; Friesenhahn, M.; Brunstein, F.; Quartino, A.; Clayton, D.; Mortensen, D.; Bittner, T.; Ho, C.; Rabe, C.; Schauer, S.P.; Wildsmith, K.R.; Fuji, R.N.; Suliman, S.; Reiman, E.M.; Chen, K.; Paul, R. Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer’s disease (BLAZE). Alzheimers Res. Ther., 2018, 10(1), 96.
[http://dx.doi.org/10.1186/s13195-018-0424-5] [PMID: 30231896]
[11]
Cryan, J.F.; O’Riordan, K.J.; Cowan, C.S.M.; Sandhu, K.V.; Bastiaanssen, T.F.S.; Boehme, M.; Codagnone, M.G.; Cussotto, S.; Fulling, C.; Golubeva, A.V.; Guzzetta, K.E.; Jaggar, M.; Long-Smith, C.M.; Lyte, J.M.; Martin, J.A.; Molinero-Perez, A.; Moloney, G.; Morelli, E.; Morillas, E.; O’Connor, R.; Cruz-Pereira, J.S.; Peterson, V.L.; Rea, K.; Ritz, N.L.; Sherwin, E.; Spichak, S.; Teichman, E.M.; van de Wouw, M.; Ventura-Silva, A.P.; Wallace-Fitzsimons, S.E.; Hyland, N.; Clarke, G.; Dinan, T.G. The microbiota-gut-brain axis. Physiol. Rev., 2019, 99(4), 1877-2013.
[http://dx.doi.org/10.1152/physrev.00018.2018] [PMID: 31460832]
[12]
La Rosa, F.; Clerici, M.; Ratto, D.; Occhinegro, A.; Licito, A.; Romeo, M.; Iorio, C.; Rossi, P. The gut-brain axis in Alzheimer’s Disease and Omega-3. A critical overview of clinical trials. Nutrients, 2018, 10(9), 1267.
[http://dx.doi.org/10.3390/nu10091267] [PMID: 30205543]
[13]
Perez-Pardo, P.; Dodiya, H.B.; Engen, P.A.; Forsyth, C.B.; Huschens, A.M.; Shaikh, M.; Voigt, R.M.; Naqib, A.; Green, S.J.; Kordower, J.H.; Shannon, K.M.; Garssen, J.; Kraneveld, A.D.; Keshavarzian, A. Role of TLR4 in the gut-brain axis in Parkinson’s disease: A translational study from men to mice. Gut, 2019, 68(5), 829-843.
[http://dx.doi.org/10.1136/gutjnl-2018-316844] [PMID: 30554160]
[14]
Valles-Colomer, M.; Falony, G.; Darzi, Y.; Tigchelaar, E.F.; Wang, J.; Tito, R.Y.; Schiweck, C.; Kurilshikov, A.; Joossens, M.; Wijmenga, C.; Claes, S.; Van Oudenhove, L.; Zhernakova, A.; Vieira-Silva, S.; Raes, J. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat. Microbiol., 2019, 4(4), 623-632.
[http://dx.doi.org/10.1038/s41564-018-0337-x] [PMID: 30718848]
[15]
Kang, D.W.; Adams, J.B.; Coleman, D.M.; Pollard, E.L.; Maldonado, J.; McDonough-Means, S.; Caporaso, J.G.; Krajmalnik-Brown, R. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci. Rep., 2019, 9(1), 5821.
[http://dx.doi.org/10.1038/s41598-019-42183-0] [PMID: 30967657]
[16]
Zhao, L.; Zhang, F.; Ding, X.; Wu, G.; Lam, Y.Y.; Wang, X.; Fu, H.; Xue, X.; Lu, C.; Ma, J.; Yu, L.; Xu, C.; Ren, Z.; Xu, Y.; Xu, S.; Shen, H.; Zhu, X.; Shi, Y.; Shen, Q.; Dong, W.; Liu, R.; Ling, Y.; Zeng, Y.; Wang, X.; Zhang, Q.; Wang, J.; Wang, L.; Wu, Y.; Zeng, B.; Wei, H.; Zhang, M.; Peng, Y.; Zhang, C. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 2018, 359(6380), 1151-1156.
[http://dx.doi.org/10.1126/science.aao5774] [PMID: 29590046]
[17]
Zhu, B.; Wang, X.; Li, L. Human gut microbiome: The second genome of human body. Protein Cell, 2010, 1(8), 718-725.
[http://dx.doi.org/10.1007/s13238-010-0093-z] [PMID: 21203913]
[18]
Quigley, E.M.M. Microbiota-brain-gut axis and neurodegenerative diseases. Curr. Neurol. Neurosci. Rep., 2017, 17(12), 94.
[http://dx.doi.org/10.1007/s11910-017-0802-6] [PMID: 29039142]
[19]
Vogt, N.M.; Kerby, R.L.; Dill-McFarland, K.A.; Harding, S.J.; Merluzzi, A.P.; Johnson, S.C.; Carlsson, C.M.; Asthana, S.; Zetterberg, H.; Blennow, K.; Bendlin, B.B.; Rey, F.E. Gut microbiome alterations in Alzheimer’s disease. Sci. Rep., 2017, 7(1), 13537.
[http://dx.doi.org/10.1038/s41598-017-13601-y] [PMID: 29051531]
[20]
Larsen, N.; Vogensen, F.K.; van den Berg, F.W.J.; Nielsen, D.S.; Andreasen, A.S.; Pedersen, B.K.; Al-Soud, W.A.; Sørensen, S.J.; Hansen, L.H.; Jakobsen, M. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One, 2010, 5(2), e9085.
[http://dx.doi.org/10.1371/journal.pone.0009085] [PMID: 20140211]
[21]
Keshavarzian, A.; Green, S.J.; Engen, P.A.; Voigt, R.M.; Naqib, A.; Forsyth, C.B.; Mutlu, E.; Shannon, K.M. Colonic bacterial composition in Parkinson’s disease. Mov. Disord., 2015, 30(10), 1351-1360.
[http://dx.doi.org/10.1002/mds.26307] [PMID: 26179554]
[22]
Cattaneo, A.; Cattane, N.; Galluzzi, S.; Provasi, S.; Lopizzo, N.; Festari, C.; Ferrari, C.; Guerra, U.P.; Paghera, B.; Muscio, C.; Bianchetti, A.; Volta, G.D.; Turla, M.; Cotelli, M.S.; Gennuso, M.; Prelle, A.; Zanetti, O.; Lussignoli, G.; Mirabile, D.; Bellandi, D.; Gentile, S.; Belotti, G.; Villani, D.; Harach, T.; Bolmont, T.; Padovani, A.; Boccardi, M.; Frisoni, G.B. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol. Aging, 2017, 49, 60-68.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.08.019] [PMID: 27776263]
[23]
Zhang, L.; Wang, Y.; Xiayu, X.; Shi, C.; Chen, W.; Song, N.; Fu, X.; Zhou, R.; Xu, Y.F.; Huang, L.; Zhu, H.; Han, Y.; Qin, C. Altered gut microbiota in a mouse model of Alzheimer’s Disease. J. Alzheimers Dis., 2017, 60(4), 1241-1257.
[http://dx.doi.org/10.3233/JAD-170020] [PMID: 29036812]
[24]
Shin, N.R.; Whon, T.W.; Bae, J.W. Proteobacteria: Microbial signature of dysbiosis in gut microbiota. Trends Biotechnol., 2015, 33(9), 496-503.
[http://dx.doi.org/10.1016/j.tibtech.2015.06.011] [PMID: 26210164]
[25]
Sun, J.; Xu, J.; Ling, Y.; Wang, F.; Gong, T.; Yang, C.; Ye, S.; Ye, K.; Wei, D.; Song, Z.; Chen, D.; Liu, J. Fecal microbiota transplantation alleviated Alzheimer’s disease-like pathogenesis in APP/PS1 transgenic mice. Transl. Psychiatry, 2019, 9(1), 189.
[http://dx.doi.org/10.1038/s41398-019-0525-3] [PMID: 31383855]
[26]
Sun, J.; Xu, J.; Yang, B.; Chen, K.; Kong, Y.; Fang, N.; Gong, T.; Wang, F.; Ling, Z.; Liu, J. Effect of Clostridium butyricum against microglia-mediated neuroinflammation in Alzheimer’s disease viaregulating gut microbiota and metabolites butyr ate. Mol. Nutr. Food Res., 2020, 64(2), 1900636.
[http://dx.doi.org/10.1002/mnfr.201900636] [PMID: 31835282]
[27]
Xiu, W.; Chen, Q.; Wang, Z.; Wang, J.; Zhou, Z. Microbiota-derived short chain fatty acid promotion of Amphiregulin expression by dendritic cells is regulated by GPR43 and Blimp-1. Biochem. Biophys. Res. Commun., 2020, 533(3), 282-288.
[http://dx.doi.org/10.1016/j.bbrc.2020.09.027] [PMID: 32958255]
[28]
Bonaz, B.; Bazin, T.; Pellissier, S. The vagus nerve at the interface of the microbiota-gut-brain axis. Front. Neurosci., 2018, 12, 49.
[http://dx.doi.org/10.3389/fnins.2018.00049] [PMID: 29467611]
[29]
Kigerl, K.A.; Zane, K.; Adams, K.; Sullivan, M.B.; Popovich, P.G. The spinal cord-gut-immune axis as a master regulator of health and neurological function after spinal cord injury. Exp. Neurol., 2020, 323, 113085.
[http://dx.doi.org/10.1016/j.expneurol.2019.113085] [PMID: 31654639]
[30]
Pascale, A.; Marchesi, N.; Marelli, C.; Coppola, A.; Luzi, L.; Govoni, S.; Giustina, A.; Gazzaruso, C. Microbiota and metabolic diseases. Endocrine, 2018, 61(3), 357-371.
[http://dx.doi.org/10.1007/s12020-018-1605-5] [PMID: 29721802]
[31]
Collins, S.M.; Surette, M.; Bercik, P. The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol., 2012, 10(11), 735-742.
[http://dx.doi.org/10.1038/nrmicro2876] [PMID: 23000955]
[32]
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]
[33]
Vourakis, M.; Mayer, G.; Rousseau, G. The role of gut microbiota on cholesterol metabolism in atherosclerosis. Int. J. Mol. Sci., 2021, 22(15), 8074.
[http://dx.doi.org/10.3390/ijms22158074] [PMID: 34360839]
[34]
Dalile, B.; Oudenhove, L.V.; Vervliet, B.; Verbeke, K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(8), 461-478.
[http://dx.doi.org/10.1038/s41575-019-0157-3] [PMID: 31123355]
[35]
Thomas, M.S.; Fernandez, M.L. Trimethylamine N-Oxide (TMAO). Curr. Atheroscler. Rep., 2021, 23(4), 12.
[http://dx.doi.org/10.1007/s11883-021-00910-x] [PMID: 33594574]
[36]
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]
[37]
Macpherson, M.E.; Hov, J.R.; Ueland, T.; Dahl, T.B.; Kummen, M.; Otterdal, K.; Holm, K.; Berge, R.K.; Mollnes, T.E.; Trøseid, M.; Halvorsen, B.; Aukrust, P.; Fevang, B.; Jørgensen, S.F. Gut microbiota-dependent trimethylamine N-oxide associates with inflammation in common variable immunodeficiency. Front. Immunol., 2020, 11, 574500.
[http://dx.doi.org/10.3389/fimmu.2020.574500] [PMID: 33042155]
[38]
Olek, R.A.; Samulak, J.J.; Sawicka, A.K.; Hartmane, D.; Grinberga, S.; Pugovics, O.; Lysiak-Szydlowska, W. Increased trimethylamine N-oxide is not associated with oxidative stress markers in healthy aged women. Oxid. Med. Cell. Longev., 2019, 2019, 1-6.
[http://dx.doi.org/10.1155/2019/6247169] [PMID: 31636806]
[39]
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]
[40]
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]
[41]
Gatarek, P.; Kaluzna-Czaplinska, J. Trimethylamine N-oxide (TMAO) in human health. EXCLI J., 2021, 20, 301-319.
[http://dx.doi.org/10.17179/excli2020-3239.] [PMID: 33746664]
[42]
Hagen, I.V.; Helland, A.; Bratlie, M.; Midttun, Ø.; McCann, A.; Sveier, H.; Rosenlund, G.; Mellgren, G.; Ueland, P.M.; Gudbrandsen, O.A. TMAO, creatine and 1-methylhistidine in serum and urine are potential biomarkers of cod and salmon intake: A randomised clinical trial in adults with overweight or obesity. Eur. J. Nutr., 2020, 59(5), 2249-2259.
[http://dx.doi.org/10.1007/s00394-019-02076-4] [PMID: 31401679]
[43]
Lidbury, I.; Murrell, J.C.; Chen, Y. Trimethylamine N -oxide metabolism by abundant marine heterotrophic bacteria. Proc. Natl. Acad. Sci. USA, 2014, 111(7), 2710-2715.
[http://dx.doi.org/10.1073/pnas.1317834111] [PMID: 24550299]
[44]
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]
[45]
Schugar, R.C.; Shih, D.M.; Warrier, M.; Helsley, R.N.; Burrows, A.; Ferguson, D.; Brown, A.L.; Gromovsky, A.D.; Heine, M.; Chatterjee, A.; Li, L.; Li, X.S.; Wang, Z.; Willard, B.; Meng, Y.; Kim, H.; Che, N.; Pan, C.; Lee, R.G.; Crooke, R.M.; Graham, M.J.; Morton, R.E.; Langefeld, C.D.; Das, S.K.; Rudel, L.L.; Zein, N.; McCullough, A.J.; Dasarathy, S.; Tang, W.H.W.; Erokwu, B.O.; Flask, C.A.; Laakso, M.; Civelek, M.; Naga Prasad, S.V.; Heeren, J.; Lusis, A.J.; Hazen, S.L.; Brown, J.M. The TMAO-producing enzyme flavin-containing monooxygenase 3 regulates obesity and the beiging of white adipose tissue. Cell Rep., 2017, 19(12), 2451-2461.
[http://dx.doi.org/10.1016/j.celrep.2017.05.077] [PMID: 28636934]
[46]
Tomlinson, J.A.P.; Wheeler, D.C. The role of trimethylamine N-oxide as a mediator of cardiovascular complications in chronic kidney disease. Kidney Int., 2017, 92(4), 809-815.
[http://dx.doi.org/10.1016/j.kint.2017.03.053] [PMID: 28807612]
[47]
Ferreira-Vieira, T.H.; Guimaraes, I.M.; Silva, F.R.; Ribeiro, F.M. Alzheimer’s disease: Targeting the cholinergic system. Curr. Neuropharmacol., 2016, 14(1), 101-115.
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[48]
Blusztajn, J.; Slack, B.; Mellott, T. Neuroprotective actions of dietary choline. Nutrients, 2017, 9(8), 815.
[http://dx.doi.org/10.3390/nu9080815] [PMID: 28788094]
[49]
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]
[50]
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.; Wu, Y.; Schauer, P.; Smith, J.D.; Allayee, H.; Tang, W.H.W.; DiDonato, J.A.; Lusis, A.J.; Hazen, S.L. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 2011, 472(7341), 57-63.
[http://dx.doi.org/10.1038/nature09922] [PMID: 21475195]
[51]
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]
[52]
Velazquez, R.; Ferreira, E.; Knowles, S.; Fux, C.; Rodin, A.; Winslow, W.; Oddo, S. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell, 2019, 18(6), e13037.
[http://dx.doi.org/10.1111/acel.13037] [PMID: 31560162]
[53]
Wang, Y.; Guan, X.; Chen, X.; Cai, Y.; Ma, Y.; Ma, J.; Zhang, Q.; Dai, L.; Fan, X.; Bai, Y. Choline supplementation ameliorates behavioral deficits and Alzheimer’s Disease-like pathology in transgenic APP/PS1 mice. Mol. Nutr. Food Res., 2019, 63(18), 1801407.
[http://dx.doi.org/10.1002/mnfr.201801407] [PMID: 31298459]
[54]
Titchenell, P.M.; Lazar, M.A.; Birnbaum, M.J. Unraveling the regulation of hepatic metabolism by insulin. Trends Endocrinol. Metab., 2017, 28(7), 497-505.
[http://dx.doi.org/10.1016/j.tem.2017.03.003] [PMID: 28416361]
[55]
Kimball, S.R.; Vary, T.C.; Jefferson, L.S. Regulation of protein synthesis by insulin. Annu. Rev. Physiol., 1994, 56(1), 321-348.
[http://dx.doi.org/10.1146/annurev.ph.56.030194.001541] [PMID: 8010743]
[56]
Cahn, A.; Miccoli, R.; Dardano, A.; Del Prato, S. New forms of insulin and insulin therapies for the treatment of type 2 diabetes. Lancet Diabetes Endocrinol., 2015, 3(8), 638-652.
[http://dx.doi.org/10.1016/S2213-8587(15)00097-2] [PMID: 26051044]
[57]
Talbot, K.; Wang, H.Y.; Kazi, H.; Han, L.Y.; Bakshi, K.P.; Stucky, A.; Fuino, R.L.; Kawaguchi, K.R.; Samoyedny, A.J.; Wilson, R.S.; Arvanitakis, Z.; Schneider, J.A.; Wolf, B.A.; Bennett, D.A.; Trojanowski, J.Q.; Arnold, S.E. Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J. Clin. Invest., 2012, 122(4), 1316-1338.
[http://dx.doi.org/10.1172/JCI59903] [PMID: 22476197]
[58]
Forner, S.; Baglietto-Vargas, D.; Martini, A.C.; Trujillo-Estrada, L.; LaFerla, F.M. Synaptic impairment in Alzheimer’s Disease: A dysregulated symphony. Trends Neurosci., 2017, 40(6), 347-357.
[http://dx.doi.org/10.1016/j.tins.2017.04.002] [PMID: 28494972]
[59]
Kellar, D.; Craft, S. Brain insulin resistance in Alzheimer’s disease and related disorders: Mechanisms and therapeutic approaches. Lancet Neurol., 2020, 19(9), 758-766.
[http://dx.doi.org/10.1016/S1474-4422(20)30231-3] [PMID: 32730766]
[60]
Govindarajulu, M.; Pinky, P.D.; Steinke, I.; Bloemer, J.; Ramesh, S.; Kariharan, T.; Rella, R.T.; Bhattacharya, S.; Dhanasekaran, M.; Suppiramaniam, V.; Amin, R.H. Gut metabolite TMAO induces synaptic plasticity deficits by promoting endoplasmic reticulum stress. Front. Mol. Neurosci., 2020, 13, 138.
[http://dx.doi.org/10.3389/fnmol.2020.00138] [PMID: 32903435]
[61]
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.; Torrecilla, E.; Vázquez, G.F.; Rubio, M.A.; Cabrerizo, L.; Barabash, A.; Pernaute, A.S.; Torres, A.J.; 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]
[62]
Tönnies, E.; Trushina, E. Oxidative stress, synaptic dysfunction, and Alzheimer's Disease. J. Alzheimers Dis., 2017, 57(4), 1105-1121.
[http://dx.doi.org/10.3233/JAD-161088] [PMID: 28059794]
[63]
Chen, M.; Zhu, X.; Ran, L.; Lang, H.; Yi, L.; Mi, M. Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway. J. Am. Heart Assoc., 2017, 6(9), e006347.
[http://dx.doi.org/10.1161/JAHA.117.006347] [PMID: 28871042]
[64]
Rohrmann, S.; Linseisen, J.; Allenspach, M.; Von Eckardstein, A.; Müller, D. Plasma concentrations of Trimethylamine-N-oxide are directly associated with dairy food consumption and low-grade inflammation in a german adult population. J. Nutr., 2016, 146(2), 283-289.
[http://dx.doi.org/10.3945/jn.115.220103] [PMID: 26674761]
[65]
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]
[66]
Meng, F.; Li, N.; Li, D.; Song, B.; Li, L. The presence of elevated circulating trimethylamine N-oxide exaggerates postoperative cognitive dysfunction in aged rats. Behav. Brain Res., 2019, 368(368), 111902.
[http://dx.doi.org/10.1016/j.bbr.2019.111902] [PMID: 30980850]
[67]
Brunt, V.E.; LaRocca, T.J.; Bazzoni, A.E.; Sapinsley, Z.J.; Miyamoto-Ditmon, J.; Gioscia-Ryan, R.A.; Neilson, A.P.; Link, C.D.; Seals, D.R. The gut microbiome–derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging. Geroscience, 2021, 43(1), 377-394.
[http://dx.doi.org/10.1007/s11357-020-00257-2] [PMID: 32862276]
[68]
Yue, C.; Yang, X.; Li, J.; Chen, X.; Zhao, X.; Chen, Y.; Wen, Y. Trimethylamine N-oxide prime NLRP3 inflammasome via inhibiting ATG16L1-induced autophagy in colonic epithelial cells. Biochem. Biophys. Res. Commun., 2017, 490(2), 541-551.
[http://dx.doi.org/10.1016/j.bbrc.2017.06.075] [PMID: 28629999]
[69]
Del Rio, D.; Zimetti, F.; Caffarra, P.; Tassotti, M.; Bernini, F.; Brighenti, F.; Zini, A.; Zanotti, I. The gut microbial metabolite trimethylamine-N-Oxide is present in human cerebrospinal fluid. Nutrients, 2017, 9(10), 1053.
[http://dx.doi.org/10.3390/nu9101053] [PMID: 28937600]
[70]
Du, D.; Tang, W.; Zhou, C.; Sun, X.; Wei, Z.; Zhong, J.; Huang, Z. Fecal microbiota transplantation is a promising method to restore gut microbiota dysbiosis and relieve neurological deficits after traumatic brain injury. Oxid. Med. Cell. Longev., 2021, 2021, 1-21.
[http://dx.doi.org/10.1155/2021/5816837] [PMID: 33628361]
[71]
Li, D.; Ke, Y.; Zhan, R.; Liu, C.; Zhao, M.; Zeng, A.; Shi, X.; Ji, L.; Cheng, S.; Pan, B.; Zheng, L.; Hong, H. Trimethylamine- N -oxide promotes brain aging and cognitive impairment in mice. Aging Cell, 2018, 17(4), e12768.
[http://dx.doi.org/10.1111/acel.12768] [PMID: 29749694]
[72]
Jian, W.; Zhang, Z.; Chu, S.; Peng, Y.; Chen, N. Potential roles of brain barrier dysfunctions in the early stage of Alzheimer’s disease. Brain Res. Bull., 2018, 142, 360-367.
[http://dx.doi.org/10.1016/j.brainresbull.2018.08.012] [PMID: 30153473]
[73]
Cai, Z.; Qiao, P.F.; Wan, C.Q.; Cai, M.; Zhou, N.K.; Li, Q. Role of blood-brain barrier in Alzheimer’s Disease. J. Alzheimers Dis., 2018, 63(4), 1223-1234.
[http://dx.doi.org/10.3233/JAD-180098] [PMID: 29782323]
[74]
Tahara, A.; Tahara, N.; Yamagishi, S.; Honda, A.; Igata, S.; Nitta, Y.; Bekki, M.; Nakamura, T.; Sugiyama, Y.; Sun, J.; Takeuchi, M.; Shimizu, M.; Yamazaki, H.; Fukami, K.; Fukumoto, Y. Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects. Int. J. Food Sci. Nutr., 2017, 68(8), 1013-1020.
[http://dx.doi.org/10.1080/09637486.2017.1318117] [PMID: 28434257]
[75]
Liu, M.; Han, Q.; Yang, J. Trimethylamine-N-oxide (TMAO) increased aquaporin-2 expression in spontaneously hypertensive rats. Clin. Exp. Hypertens., 2019, 41(4), 312-322.
[http://dx.doi.org/10.1080/10641963.2018.1481420] [PMID: 29985655]
[76]
Boini, K.M.; Hussain, T.; Li, P.L.; Koka, S.S. Trimethylamine-N-Oxide Instigates NLRP3 Inflammasome Activation and Endothelial Dysfunction. Cell. Physiol. Biochem., 2017, 44(1), 152-162.
[http://dx.doi.org/10.1159/000484623] [PMID: 29130962]
[77]
Obrenovich, M.; Siddiqui, B.; McCloskey, B.; Reddy, V.P. The microbiota–gut–brain axis heart Shunt Part I: The French paradox, heart disease and the microbiota. Microorganisms, 2020, 8(4), 490.
[http://dx.doi.org/10.3390/microorganisms8040490] [PMID: 32235574]
[78]
Vernetti, L.; Gough, A.; Baetz, N.; Blutt, S.; Broughman, J.R.; Brown, J.A.; Foulke-Abel, J.; Hasan, N.; In, J.; Kelly, E.; Kovbasnjuk, O.; Repper, J.; Senutovitch, N.; Stabb, J.; Yeung, C.; Zachos, N.C.; Donowitz, M.; Estes, M.; Himmelfarb, J.; Truskey, G.; Wikswo, J.P.; Taylor, D.L. Functional coupling of human microphysiology systems: Intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Sci. Rep., 2017, 7(1), 42296.
[http://dx.doi.org/10.1038/srep42296] [PMID: 28176881]
[79]
Xu, R.; Wang, Q. Towards understanding brain-gut-microbiome connections in Alzheimer’s disease. BMC Syst. Biol., 2016, 10(S3), 63.
[http://dx.doi.org/10.1186/s12918-016-0307-y] [PMID: 27585440]
[80]
Kumari, A.; Rajput, R.; Shrivastava, N.; Somvanshi, P.; Grover, A. Synergistic approaches unraveling regulation and aggregation of intrinsically disordered β-amyloids implicated in Alzheimer’s disease. Int. J. Biochem. Cell Biol., 2018, 99, 19-27.
[http://dx.doi.org/10.1016/j.biocel.2018.03.014] [PMID: 29571707]
[81]
Gao, Q.; Wang, Y.; Wang, X.; Fu, S.; Zhang, X.; Wang, R.T.; Zhang, X. Decreased levels of circulating trimethylamine N-oxide alleviate cognitive and pathological deterioration in transgenic mice: A potential therapeutic approach for Alzheimer’s disease. Aging, 2019, 11(19), 8642-8663.
[http://dx.doi.org/10.18632/aging.102352] [PMID: 31612864]
[82]
Wang, Q.J.; Shen, Y.E.; Wang, X.; Fu, S.; Zhang, X.; Zhang, Y.N.; Wang, R.T. Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice. aging, 2020, 12(1), 628-649.
[http://dx.doi.org/10.18632/aging.102645] [PMID: 31907339]
[83]
Roncal, C.; Martínez-Aguilar, E.; Orbe, J.; Ravassa, S.; Fernandez-Montero, A.; Saenz-Pipaon, G.; Ugarte, A.; Estella-Hermoso de Mendoza, A.; Rodriguez, J.A.; Fernández-Alonso, S.; Fernández-Alonso, 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]
[84]
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-Hansen, 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]
[85]
Skagen, K.; Trøseid, M.; Ueland, T.; Holm, S.; Abbas, A.; Gregersen, I.; Kummen, M.; Bjerkeli, V.; Reier-Nilsen, 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]
[86]
Kapetanaki, S.; Kumawat, A.K.; Persson, K.; Demirel, I. The fibrotic effects of TMAO on human renal fibroblasts is mediated by NLRP3, Caspase-1 and the PERK/Akt/mTOR pathway. Int. J. Mol. Sci., 2021, 22(21), 11864.
[http://dx.doi.org/10.3390/ijms222111864] [PMID: 34769294]
[87]
Li, Z.; Wu, Z.; Yan, J.; Liu, H.; Liu, Q.; Deng, Y.; Ou, C.; Chen, M. Gut microbe-derived metabolite trimethylamine N-oxide induces cardiac hypertrophy and fibrosis. Lab. Invest., 2019, 99(3), 346-357.
[http://dx.doi.org/10.1038/s41374-018-0091-y] [PMID: 30068915]
[88]
Sun, X.; Jiao, X.; Ma, Y.; Liu, Y.; Zhang, L.; He, Y.; Chen, Y. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochem. Biophys. Res. Commun., 2016, 481(1-2), 63-70.
[http://dx.doi.org/10.1016/j.bbrc.2016.11.017] [PMID: 27833015]
[89]
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), 888-894.
[http://dx.doi.org/10.3945/ajcn.117.157107] [PMID: 28724646]
[90]
León-Mimila, P.; Villamil-Ramírez, H.; Li, X.S.; Shih, D.M.; Hui, S.T.; Ocampo-Medina, E.; López-Contreras, B.; Morán-Ramos, S.; Olivares-Arevalo, M.; Grandini-Rosales, P.; Macías-Kauffer, L.; González-González, I.; Hernández-Pando, R.; Gómez-Pérez, F.; Campos-Pérez, F.; Aguilar-Salinas, C.; Larrieta-Carrasco, E.; Villarreal-Molina, T.; Wang, Z.; Lusis, A.J.; Hazen, S.L.; Huertas-Vazquez, A.; Canizales-Quinteros, 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]
[91]
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]
[92]
Ke, Y.; Li, D.; Zhao, M.; Liu, C.; Liu, J.; Zeng, A.; Shi, X.; Cheng, S.; Pan, B.; Zheng, L.; Hong, H. Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Free Radic. Biol. Med., 2018, 116, 88-100.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.01.007] [PMID: 29325896]
[93]
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]
[94]
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]
[95]
Lin, H.; Liu, T.; Li, X.; Gao, X.; Wu, T.; Li, P. The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease. Ann. Transl. Med., 2020, 8(16), 1009-1009.
[http://dx.doi.org/10.21037/atm-20-5307] [PMID: 32953809]
[96]
Cho, C.E.; Taesuwan, S.; Malysheva, O.V.; Bender, E.; Tulchinsky, N.F.; Yan, J.; Sutter, J.L.; Caudill, M.A. Trimethylamine- N -oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol. Nutr. Food Res., 2017, 61(1), 1600324.
[http://dx.doi.org/10.1002/mnfr.201600324] [PMID: 27377678]
[97]
Manor, O.; Zubair, N.; Conomos, M.P.; Xu, X.; Rohwer, J.E.; Krafft, C.E.; Lovejoy, J.C.; Magis, A.T. A multi-omic association study of trimethylamine N-Oxide. Cell Rep., 2018, 24(4), 935-946.
[http://dx.doi.org/10.1016/j.celrep.2018.06.096] [PMID: 30044989]
[98]
Chen, M.; Yi, L.; Zhang, Y.; Zhou, X.; Ran, L.; Yang, J.; Zhu, J.; Zhang, Q.; Mi, M. Resveratrol attenuates trimethylamine- N -Oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota. MBio, 2016, 7(2), e02210-15.
[http://dx.doi.org/10.1128/mBio.02210-15] [PMID: 27048804]
[99]
Shi, Y.; Hu, J.; Geng, J.; Hu, T.; Wang, B.; Yan, W.; Jiang, Y.; Li, J.; Liu, S. Berberine treatment reduces atherosclerosis by mediating gut microbiota in apoE-/- mice. Biomed. Pharmacother., 2018, 107, 1556-1563.
[http://dx.doi.org/10.1016/j.biopha.2018.08.148] [PMID: 30257374]
[100]
Romano, K.A.; Vivas, E.I.; Amador-Noguez, D.; Rey, F.E. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. MBio, 2015, 6(2), e02481-14.
[http://dx.doi.org/10.1128/mBio.02481-14] [PMID: 25784704]
[101]
Ji, C.; Li, Y.; Mo, Y.; Lu, Z.; Lu, F.; Lin, Q.; Liu, X.; Zou, C.; Wu, Y. Rhubarb enema decreases circulating trimethylamine N-oxide level and improves renal fibrosis accompanied with gut microbiota change in chronic kidney disease rats. Front. Pharmacol., 2021, 12, 780924.
[http://dx.doi.org/10.3389/fphar.2021.780924] [PMID: 34966280]
[102]
Hsu, C.N.; Yang, H.W.; Hou, C.Y.; Chang-Chien, G.P.; Lin, S.; Tain, Y.L. Melatonin prevents chronic kidney disease-induced hypertension in young rat treated with adenine: Implications of gut microbiota-derived metabolites. Antioxidants, 2021, 10(8), 1211.
[http://dx.doi.org/10.3390/antiox10081211] [PMID: 34439458]
[103]
Yoo, W.; Zieba, J.K.; Foegeding, N.J.; Torres, T.P.; Shelton, C.D.; Shealy, N.G.; Byndloss, A.J.; Cevallos, S.A.; Gertz, E.; Tiffany, C.R.; Thomas, J.D.; Litvak, Y.; Nguyen, H.; Olsan, E.E.; Bennett, B.J.; Rathmell, J.C.; Major, A.S.; Bäumler, A.J.; Byndloss, M.X. High-fat diet–induced colonocyte dysfunction escalates microbiota-derived trimethylamine N -oxide. Science, 2021, 373(6556), 813-818.
[http://dx.doi.org/10.1126/science.aba3683] [PMID: 34385401]
[104]
Kuka, J.; Videja, M.; Makrecka-Kuka, M.; Liepins, J.; Grinberga, S.; Sevostjanovs, E.; Vilks, K.; Liepinsh, E.; Dambrova, M. Metformin decreases bacterial trimethylamine production and trimethylamine N-oxide levels in db/db mice. Sci. Rep., 2020, 10(1), 14555.
[http://dx.doi.org/10.1038/s41598-020-71470-4] [PMID: 32884086]
[105]
Ramireddy, L.; Tsen, H.Y.; Chiang, Y.C.; Hung, C.Y.; Chen, F.C.; Yen, H.T. The gene expression and bioinformatic analysis of choline trimethylamine-lyase (CutC) and its activating enzyme (CutD) for gut microbes and comparison with their TMA production levels. Curr. Res. Microb. Sci., 2021, 2, 100043.
[http://dx.doi.org/10.1016/j.crmicr.2021.100043] [PMID: 34841334]
[106]
Panyod, S.; Wu, W.K.; Chen, P.C.; Chong, K.V.; Yang, Y.T.; Chuang, H.L.; Chen, C.C.; Chen, R.A.; Liu, P.Y.; Chung, C.H.; Huang, H.S.; Lin, A.Y.C.; Shen, T.C.D.; Yang, K.C.; Huang, T.F.; Hsu, C.C.; Ho, C.T.; Kao, H.L.; Orekhov, A.N.; Wu, M.S.; Sheen, L.Y. Atherosclerosis amelioration by allicin in raw garlic through gut microbiota and trimethylamine-N-oxide modulation. NPJ Biofilms. Microbiomes, 2022, 8(1), 4.
[http://dx.doi.org/10.1038/s41522-022-00266-3] [PMID: 35087050]
[107]
Liu, S.; He, F.; Zheng, T.; Wan, S.; Chen, J.; Yang, F.; Xu, X.; Pei, X. Ligustrum robustum alleviates atherosclerosis by decreasing Serum TMAO, modulating gut microbiota, and decreasing bile acid and cholesterol absorption in mice. Mol. Nutr. Food Res., 2021, 65(14), 2100014.
[http://dx.doi.org/10.1002/mnfr.202100014] [PMID: 34005835]
[108]
Wang, Q.; Guo, M.; Liu, Y.; Xu, M.; Shi, L.; Li, X.; Zhao, J.; Zhang, H.; Wang, G.; Chen, W. Bifidobacterium breve and Bifidobacterium longum attenuate choline-induced plasma trimethylamine N-oxide production by modulating gut microbiota in mice. Nutrients, 2022, 14(6), 1222.
[http://dx.doi.org/10.3390/nu14061222] [PMID: 35334879]
[109]
Wang, X.; Li, X.; Dong, Y. Vitamin D decreases plasma trimethylamine-N-oxide level in mice by regulating gut microbiota. BioMed Res. Int., 2020, 2020, 1-11.
[http://dx.doi.org/10.1155/2020/9896743] [PMID: 33083493]
[110]
Sardu, C.; Consiglia Trotta, M.; Santella, B.; D’Onofrio, N.; Barbieri, M.; Rizzo, M.R.; Sasso, F.C.; Scisciola, L.; Turriziani, F.; Torella, M.; Portoghese, M.; Loreni, F.; Mureddu, S.; Lepore, M.A.; Galdiero, M.; Franci, G.; Folliero, V.; Petrillo, A.; Boatti, L.; Minicucci, F.; Mauro, C.; Calabrò, P.; Feo, M.D.; Balestrieri, M.L.; Ercolini, D.; D’Amico, M.; Paolisso, G.; Galdiero, M.; Marfella, R. Microbiota thrombus colonization may influence athero-thrombosis in hyperglycemic patients with ST segment elevation myocardialinfarction (STEMI). Marianella study. Diabetes Res. Clin. Pract., 2021, 173, 108670.
[http://dx.doi.org/10.1016/j.diabres.2021.108670] [PMID: 33453294]
[111]
Li, Q.; Larouche-Lebel, É.; Loughran, K.A.; Huh, T.P.; Suchodolski, J.S.; Oyama, M.A. Gut dysbiosis and its associations with gut microbiota-derived metabolites in dogs with myxomatous mitral valve disease. mSystems, 2021, 6(2), e00111-21.
[http://dx.doi.org/10.1128/mSystems.00111-21] [PMID: 33879495]
[112]
Shirouchi, B.; Fukuda, A.; Akasaka, T. Unlike glycerophosphocholine or choline chloride, dietary phosphatidylcholine does not increase plasma trimethylamine-N-oxide levels in sprague-dawley rats. Metabolites, 2022, 12(1), 64.
[http://dx.doi.org/10.3390/metabo12010064] [PMID: 35050186]
[113]
James, K.L.; Gertz, E.R.; Cervantes, E.; Bonnel, E.L.; Stephensen, C.B.; Kable, M.E.; Bennett, B.J. Diet, fecal microbiome, and trimethylamine N-oxide in a cohort of metabolically healthy united states adults. Nutrients, 2022, 14(7), 1376.
[http://dx.doi.org/10.3390/nu14071376] [PMID: 35405993]
[114]
Zhu, L.; Wang, J.; Ding, X.; Bai, S.; Zeng, Q.; Xuan, Y.; Fraley, G.S.; Zhang, K. Serum trimethylamine-N-oxide and gut microbiome alterations are associated with cholesterol deposition in the liver of laying hens fed with rapeseed meal. Anim. Nutr., 2021, 7(4), 1258-1270.
[http://dx.doi.org/10.1016/j.aninu.2021.02.008] [PMID: 34786499]
[115]
Wu, D.; Cao, M.; Li, N.; Zhang, A.; Yu, Z.; Cheng, J.; Xie, X.; Wang, Z.; Lu, S.; Yan, S.; Zhou, J.; Peng, J.; Zhao, J. Effect of trimethylamine N-oxide on inflammation and the gut microbiota in Helicobacter pylori-infected mice. Int. Immunopharmacol., 2020, 81, 106026.
[http://dx.doi.org/10.1016/j.intimp.2019.106026] [PMID: 31759863]
[116]
Calderón-Pérez, L.; José Gosalbes, M.; Yuste, S.; Valls, R.M.; Pedret, A.; Llauradó, E.; Jimenez-Hernandez, N.; Artacho, A.; Pla-Pagà, L.; Companys, J.; Ludwig, I.; Romero, M-P.; Rubió, L.; Solà, R. Gut metagenomic and short chain fatty acids signature in hypertension: A cross-sectional study. Sci Rep., 2020, 10(1), 6436.
[http://dx.doi.org/10.1038/s41598-020-63475-w.] [PMID: 32296109]
[117]
Nahok, K.; Phetcharaburanin, J.; Li, J.V.; Silsirivanit, A.; Thanan, R.; Boonnate, P.; Joonhuathon, J.; Sharma, A.; Anutrakulchai, S.; Selmi, C.; Cha’on, U. Monosodium glutamate induces changes in hepatic and renal metabolic profiles and gut microbiome of wistar rats. Nutrients, 2021, 13(6), 1865.
[http://dx.doi.org/10.3390/nu13061865] [PMID: 34070818]
[118]
Genoni, A.; Christophersen, C.T.; Lo, J.; Coghlan, M.; Boyce, M.C.; Bird, A.R.; Lyons-Wall, P.; Devine, A. Long-term Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentrations. Eur. J. Nutr., 2020, 59(5), 1845-1858.
[http://dx.doi.org/10.1007/s00394-019-02036-y] [PMID: 31273523]
[119]
Sánchez-Alcoholado, L.; Ordóñez, R.; Otero, A.; Plaza-Andrade, I.; Laborda-Illanes, A.; Medina, J.A.; Ramos-Molina, B.; Gómez-Millán, J.; Queipo-Ortuño, M.I. Gut microbiota-mediated inflammation and gut permeability in patients with obesity and colorectal cancer. Int. J. Mol. Sci., 2020, 21(18), 6782.
[http://dx.doi.org/10.3390/ijms21186782] [PMID: 32947866]
[120]
Gao, J.; Yan, K.T.; Wang, J.X.; Dou, J.; Wang, J.; Ren, M.; Ma, J.; Zhang, X.; Liu, Y. Gut microbial taxa as potential predictive biomarkers for acute coronary syndrome and post-STEMI cardiovascular events. Sci. Rep., 2020, 10(1), 2639.
[http://dx.doi.org/10.1038/s41598-020-59235-5] [PMID: 32060329]
[121]
Shi, Q.; Wang, Q.; Zhong, H.; Li, D.; Yu, S.; Yang, H.; Wang, C.; Yin, Z. Roux-en-Y gastric bypass improved insulin resistance via alteration of the human gut microbiome and alleviation of endotoxemia. BioMed Res. Int., 2021, 2021, 1-14.
[http://dx.doi.org/10.1155/2021/5554991] [PMID: 34337024]
[122]
Adak, A.; Khan, M.R. An insight into gut microbiota and its functionalities. Cell. Mol. Life Sci., 2019, 76(3), 473-493.
[http://dx.doi.org/10.1007/s00018-018-2943-4] [PMID: 30317530]
[123]
Maqsood, R.; Stone, T.W. The gut-brain axis, BDNF, NMDA and CNS disorders. Neurochem. Res., 2016, 41(11), 2819-2835.
[http://dx.doi.org/10.1007/s11064-016-2039-1] [PMID: 27553784]
[124]
Pröbstel, A.K.; Zhou, X.; Baumann, R.; Wischnewski, S.; Kutza, M.; Rojas, O.L.; Sellrie, K.; Bischof, A.; Kim, K.; Ramesh, A.; Dandekar, R.; Greenfield, A.L.; Schubert, R.D.; Bisanz, J.E.; Vistnes, S.; Khaleghi, K.; Landefeld, J.; Kirkish, G.; Liesche-Starnecker, F.; Ramaglia, V.; Singh, S.; Tran, E.B.; Barba, P.; Zorn, K.; Oechtering, J.; Forsberg, K.; Shiow, L.R.; Henry, R.G.; Graves, J.; Cree, B.A.C.; Hauser, S.L.; Kuhle, J.; Gelfand, J.M.; Andersen, P.M.; Schlegel, J.; Turnbaugh, P.J.; Seeberger, P.H.; Gommerman, J.L.; Wilson, M.R.; Schirmer, L.; Baranzini, S.E. Gut microbiota–specific IgA + B cells traffic to the CNS in active multiple sclerosis. Sci. Immunol., 2020, 5(53), eabc7191.
[http://dx.doi.org/10.1126/sciimmunol.abc7191] [PMID: 33219152]
[125]
Rutsch, A.; Kantsjö, J.B.; Ronchi, F. The gut-brain axis: How microbiota and host inflammasome influence brain physiology and pathology. Front. Immunol., 2020, 11, 604179.
[http://dx.doi.org/10.3389/fimmu.2020.604179] [PMID: 33362788]

Rights & Permissions Print Cite
Article Metrics
45
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy