Volume 10, Issue 1 (Winter 2021)                   JOHE 2021, 10(1): 17-23 | Back to browse issues page


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Khodabakhshi A, Rooholamini M R. Is There any Possible Association Between Trimethylamine N-Oxide (TMAO) and Cancer? A Review Study. JOHE. 2021; 10 (1) :17-23
URL: http://johe.rums.ac.ir/article-1-424-en.html
1- Assistant Prof, Dept. of Nutrition, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran. , khodabakhshiadeleh@yahoo.com
2- Undergraduate Student, Dept. of Nutrition, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran.
Abstract:   (446 Views)

Background: During the transit of digested animal source foods, gut microbiota synthesize metabolites that can affect the body cells. One of these metabolites, i.e. Trimethylamine (TMA) that is an intermediary metabolite, ultimately leads to the production of Trimethylamine N-oxide (TMAO). Several studies have been conducted to show the association between TMAO and different diseases. This article aimed to search literature in order to review published findings about the possible association between TMAO and cancer.
Materials and Methods: In this literature review, a comprehensive electronic search of different databases was done using "Trimethylamine N-oxide" and "cancer" as the main keywords.
Result: Research suggests that TMAO can be related to the increased risk of cancer. The results showed a higher level of serum TMAO in cancer patients, most importantly colorectal cancer (CRC), than in healthy controls.  Nevertheless, inflammation, oxidative stress, and DNA damage could be the reasons for the link between TMAO and cancer. Limiting dietary intake of animal products can reduce levels of TMAO.
Conclusion: It is concluded that a higher rate of TMAO production could potentially be associated with the development of different types of cancers, particularly CRC.

Full-Text [PDF 421 kb]   (142 Downloads) |   |   Full-Text (HTML)  (144 Views)  
Type of Study: Review Article | Subject: Epidemiology
Received: 2021/03/24 | Accepted: 2021/06/2 | ePublished: 2021/06/21

References
1. Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2020; 70(4):313. [DOI] [PMID]
2. Institute of Medicine (US) Committee on Cancer Control in Low- and Middle-Income Countries. Cancer Control Opportunities in Low- and Middle-Income Countries. Sloan FA, Gelband H, editors. Washington (DC): National Academies Press (US); 2007. Chapter 2, Cancer causes and risk factors and the elements of cancer control. [DOI] [PMID] [Bookshelf ID]
3. Gold EB, Gordis L, Diener MD, Seltser R, Boitnott JK, Bynum TE, et al. Diet and other risk factors for cancer of the pancreas. Cancer 1985; 55(2):460-7. [DOI] [PMID]
4. Wu S, Powers S, Zhu W, Hannun YA. Substantial contribution of extrinsic risk factors to cancer development. Nature 2016; 529(7584):43-7. [DOI] [PMID] [PMCID]
5. Chhibber-Goel J, Singhal V, Parakh N, Bhargava B, Sharma A. The Metabolite Trimethylamine-N-Oxide is an Emergent Biomarker of Human Health. Curr Med Chem 2017; 24(36):3942-53. [DOI] [PMID]
6. Raymond JL, Morrow K. Krause and Mahan’s Food & the Nutrition Care Process. 15th ed. Philadelphia, United States: Saunders; 2020.
7. Demarquoy J, Georges B, Rigault C, Royer MC, Clairet A, Soty M, et al. Radioisotopic determination of L-carnitine content in foods commonly eaten in Western countries. Food Chem 2004; 86(1):137-42. [DOI]
8. Zeisel SH, da Costa KA. Choline: an essential nutrient for public health. Nutr Rev 2009; 67(11):615-23. [DOI] [PMID] [PMCID]
9. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472(7341):57-63. [DOI] [PMID] [PMCID]
10. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368(17):1575-84. [DOI] [PMID] [PMCID]
11. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013; 19(5):576-85. [DOI] [PMID] [PMCID]
12. Chamcheu JC, Navsaria H, Pihl-Lundin I, Liovic M, Vahlquist A, Törmä H. Chemical chaperones protect epidermolysis bullosa simplex keratinocytes from heat stress–induced keratin aggregation: involvement of heat shock proteins and MAP kinases. J Invest Dermatol 2011; 131(8):1684-91. [DOI] [PMID]
13. Trøseid M, Ueland T, Hov JR, Svardal A, Gregersen I, Dahl CP, et al. 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):717-26. [DOI] [PMID]
14. Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, et al. 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):448-55. [DOI] [PMID] [PMCID]
15. Oellgaard J, Winther SA, Hansen TS, Rossing P, von Scholten BJ. Trimethylamine N-oxide (TMAO) as a New Potential Therapeutic Target for Insulin Resistance and Cancer. Curr Pharm Des 2017; 23(25):3699-712. [DOI] [PMID]
16. Zitvogel L, Galluzzi L, Viaud S, Vétizou M, Daillère R, Merad M, et al. Cancer and the gut microbiota: an unexpected link. Sci Transl Med 2015; 7(271):271ps1. [DOI] [PMID] [PMCID]
17. Ufnal M, Zadlo A, Ostaszewski R. TMAO: A small molecule of great expectations. Nutrition 2015; 31(11-12):1317-23. [DOI] [PMID]
18. Zeisel SH, da Costa KA. Choline: an essential nutrient for public health. Nutr Rev 2009; 67(11):615-23. [DOI] [PMID] [PMCID]
19. Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, et al. Trimethylamine-N-Oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab 2013; 17(1):49-60. [DOI] [PMID] [PMCID]
20. Coutinho-Wolino KS, de F Cardozo LFM, de Oliveira Leal V, Mafra D, Stockler-Pinto MB. Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far? Eur J Nutr 2021; doi:10.1007/s00394-021-02491-6 [DOI] [PMID]
21. Oellgaard J, Winther SA, Hansen TS, Rossing P, von Scholten BJ. Trimethylamine N-oxide (TMAO) as a New Potential Therapeutic Target for Insulin Resistance and Cancer. Curr Pharm Des 2017; 23(25):3699-712. [DOI] [PMID]
22. Bartsch H, Montesano R. Relevance of nitrosamines to human cancer. Carcinogenesis 1984; 5(11):1381-93. [DOI] [PMID]
23. Guertin KA, Li XS, Graubard BI, Albanes D, Weinstein SJ, Goedert JJ, et al. 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):945-52. [DOI] [PMID] [PMCID]
24. Liu X, Liu H, Yuan C, Zhang Y, Wang W, Hu S, et al. Preoperative serum TMAO level is a new prognostic marker for colorectal cancer. Biomark Med 2017; 11(5):443-7. [DOI] [PMID]
25. Bae S, Ulrich CM, Neuhouser ML, Malysheva O, Bailey LB, Xiao L, et al. Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study. Cancer Res 2014; 74(24):7442-52. [DOI] [PMID] [PMCID]
26. Georgescauld F, Mocan I, Lacombe ML, Lascu I. Rescue of the neuroblastoma mutant of the human nucleoside diphosphate kinase A/nm23-H1 by the natural osmolyte trimethylamine-N-oxide. FEBS Lett 2009; 583(4):820-4. [DOI] [PMID]
27. Kirby TW, Derose EF, Beard WA, Shock DD, Wilson SH, London RE. Substrate rescue of DNA polymerase β containing a catastrophic L22P mutation. Biochemistry 2014; 53(14):2413-22. [DOI] [PMID] [PMCID]
28. Bhat MY, Singh LR, Dar TA. Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein. Sci Rep 2017; 7(1):6572. [DOI] [PMID] [PMCID]
29. Bonuccelli G, Castello-Cros R, Capozza F, Martinez-Outschoorn UE, Lin Z, Tsirigos A, et al. The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis. Cell Cycle 2012; 11(21):3972-82. [DOI] [PMID] [PMCID]
30. Seldin MM, Meng Y, Qi H, Zhu W, Wang Z, Hazen SL, et al. Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB. J Am Heart Assoc 2016; 5(2):e002767. [DOI] [PMID] [PMCID]
31. 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):283-9. [DOI] [PMID]
32. Xuan C, Shamonki JM, Chung A, DiNome ML, Chung M, Sieling PA, et al. Microbial dysbiosis is associated with human breast cancer. PloS One 2014; 9(1):e83744. [DOI] [PMID] [PMCID]
33. Brawner KM, Morrow CD, Smith PD. Gastric microbiome and gastric cancer. Cancer J 2014; 20(3):211-6. [DOI] [PMID] [PMCID]
34. Li T, Chen Y, Gua C, Li X. Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress. Front Physiol 2017; 8:350. [DOI] [PMID] [PMCID]
35. Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 2007; 121(11):2381-6. [DOI] [PMID]
36. Xu R, Wang Q, Li L. A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. BMC Genomics 2015; 16 Suppl 7(Suppl 7):S4. [DOI] [PMID] [PMCID]
37. Norat T, Bingham S, Ferrari P, Slimani N, Jenab M, Mazuir M, et al. Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition. J Natl Cancer Inst 2005; 97(12):906-16. [DOI] [PMID] [PMCID]
38. Chan CWH, Law BMH, Waye MMY, Chan JYW, So WKW, Chow KM. Trimethylamine-N-oxide as One Hypothetical Link for the Relationship between Intestinal Microbiota and Cancer - Where We Are and Where Shall We Go? J Cancer 2019; 10(23):5874-82. [DOI] [PMID] [PMCID]
39. Kaźmierczak-Siedlecka K, Daca A, Fic M, van de Wetering T, Folwarski M, Makarewicz W. Therapeutic methods of gut microbiota modification in colorectal cancer management – fecal microbiota transplantation, prebiotics, probiotics, and synbiotics. Gut Microbes 2020; 11(6):1518-30. [DOI] [PMID] [PMCID]
40. Parker KD, Maurya AK, Ibrahim H, Rao S, Hove PR, Kumar D, et al. Dietary Rice Bran-Modified Human Gut Microbial Consortia Confers Protection against Colon Carcinogenesis Following Fecal Transfaunation. Biomedicines 2021; 9(2):144. [DOI] [PMID] [PMCID]
41. Griffin LE, Djuric Z, Angiletta CJ, Mitchell CM, Baugh ME, Davy KP, et al. A Mediterranean diet does not alter plasma trimethylamine N-oxide concentrations in healthy adults at risk for colon cancer. Food Funct 2019; 10(4):2138-47. [DOI] [PMID] [PMCID]
42. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013; 19(5):576-85. [DOI] [PMID] [PMCID]
43. Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, et al. 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). doi: 10.1002/mnfr.201600324 [DOI] [PMID]
44. Krüger R, Merz B, Rist MJ, Ferrario PG, Bub A, Kulling SE, et al. Associations of current diet with plasma and urine TMAO in the KarMeN study: direct and indirect contributions. Mol Nutr Food Res 2017; 61(11). doi: 10.1002/mnfr.201700363 [DOI] [PMID]
45. Yu XF, Zou J, Dong J. Fish consumption and risk of gastrointestinal cancers: a meta-analysis of cohort studies. World J Gastroenterol 2014; 20(41):15398-412. [DOI] [PMID] [PMCID]
46. Xu R, Wang Q, Li L. A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. BMC Genomics 2015; 16 Suppl 7(Suppl 7):S4. [DOI] [PMID] [PMCID]
47. Liu ZY, Tan XY, Li QJ, Liao GC, Fang AP, Zhang DM, et al. 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 (Lond) 2018; 15:81. [DOI] [PMID] [PMCID]
48. Mondul AM, Moore SC, Weinstein SJ, Karoly ED, Sampson JN, Albanes D. Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha‐tocopherol, beta‐carotene cancer prevention (ATBC) study. Int J Cancer 2015; 137(9):2124-32. [DOI] [PMID] [PMCID]
49. Bag S, Banerjee DR, Basak A, Das AK, Pal M, Banerjee R, et al. NMR ((1)H and (13)C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect. Biochem Biophys Res Commun 2015; 459(4):574-8. [DOI] [PMID]
50. Khodabakhshi A, Akbari ME, Mirzaei HR, Mehrad-Majd H, Kalamian M, Davoodi SH. Feasibility, Safety, and Beneficial Effects of MCT-Based Ketogenic Diet for Breast Cancer Treatment: A Randomized Controlled Trial Study. Nutr Cancer 2020; 72(4):627-34. [DOI] [PMID]
51. Khodabakhshi A, Seyfried TN, Kalamian M, Beheshti M, Davoodi SH. Does a ketogenic diet have beneficial effects on quality of life, physical activity or biomarkers in patients with breast cancer: a randomized controlled clinical trial. Nutr J 2020; 19(1):87. [DOI] [PMID] [PMCID]
52. Khodabakhshi A, Akbari ME, Mirzaei HR, Seyfried TN, Kalamian M, Davoodi SH. Effects of Ketogenic metabolic therapy on patients with breast cancer: A randomized controlled clinical trial. Clin Nutr 2021; 40(3):751-8. [DOI] [PMID]
53. Khodabakhshi A, Mahmoudi M, Mehrad Majd H, Davoodi SH. Possible Nutrition-Related Mechanisms of Metabolic Management in Cancer Treatment. Int J Cancer Manag 2021; 14(1):e107678. [DOI]

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