Microbiota Effect on Trimethylamine N-Oxide Production: From Cancer to Fitness-A Practical Preventing Recommendation and Therapies

Overview

Journal Nutrients

Date 2023 Feb 11

PMID 36771270

Authors

Edoardo Tacconi

Giuseppe Palma

Davide De Biase

Antonio Luciano

Massimiliano Barbieri

Filomena de Nigris

Francesca Bruzzese

Affiliations

Soon will be listed here.

Abstract

Trimethylamine N-oxide (TMAO) is a microbial metabolite derived from nutrients, such as choline, L-carnitine, ergothioneine and betaine. Recently, it has come under the spotlight for its close interactions with gut microbiota and implications for gastrointestinal cancers, cardiovascular disease, and systemic inflammation. The culprits in the origin of these pathologies may be food sources, in particular, high fat meat, offal, egg yolk, whole dairy products, and fatty fish, but intercalated between these food sources and the production of pro-inflammatory TMAO, the composition of gut microbiota plays an important role in modulating this process. The aim of this review is to explain how the gut microbiota interacts with the conversion of specific compounds into TMA and its oxidation to TMAO. We will first cover the correlation between TMAO and various pathologies such as dysbiosis, then focus on cardiovascular disease, with a particular emphasis on pro-atherogenic factors, and then on systemic inflammation and gastrointestinal cancers. Finally, we will discuss primary prevention and therapies that are or may become possible. Possible treatments include modulation of the gut microbiota species with diets, physical activity and supplements, and administration of drugs, such as metformin and aspirin.

Citing Articles

Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin.

Ma X, Sun C, Ding X, Zhang Y, Deng T, Wang Y Front Oncol. 2025; 15:1482050.

PMID: 39944825 PMC: 11814469. DOI: 10.3389/fonc.2025.1482050.

Effect of Gut Dysbiosis on Onset of GI Cancers.

Kumari S, Srilatha M, Nagaraju G Cancers (Basel). 2025; 17(1.

PMID: 39796717 PMC: 11720164. DOI: 10.3390/cancers17010090.

A Case-Control Study of Dietary Choline Intake and Risk of Colorectal Cancer Modified by Dietary B-Vitamin Intake.

Chen A, Matich E, Laryea J, Hsu P, Su L Nutrients. 2024; 16(23).

PMID: 39683593 PMC: 11644455. DOI: 10.3390/nu16234200.

Intestinal Insights: The Gut Microbiome's Role in Atherosclerotic Disease: A Narrative Review.

Alexandrescu L, Suceveanu A, Stanigut A, Tofolean D, Axelerad A, Iordache I Microorganisms. 2024; 12(11).

PMID: 39597729 PMC: 11596410. DOI: 10.3390/microorganisms12112341.

The Role of Gut Microbiota in the Onset and Progression of Obesity and Associated Comorbidities.

Enache R, Profir M, Rosu O, Cretoiu S, Gaspar B Int J Mol Sci. 2024; 25(22).

PMID: 39596385 PMC: 11595101. DOI: 10.3390/ijms252212321.

References

Robbiano L, Mereto E, Corbu C, Brambilla G . DNA damage induced by seven N-nitroso compounds in primary cultures of human and rat kidney cells. Mutat Res. 1996; 368(1):41-7. DOI: 10.1016/s0165-1218(96)90038-5. View

Park J, von Karsa L, Herrero R . Prevention strategies for gastric cancer: a global perspective. Clin Endosc. 2014; 47(6):478-89. PMC: 4260094. DOI: 10.5946/ce.2014.47.6.478. View

Tripolt N, Leber B, Triebl A, Kofeler H, Stadlbauer V, Sourij H . Effect of Lactobacillus casei Shirota supplementation on trimethylamine-N-oxide levels in patients with metabolic syndrome: An open-label, randomized study. Atherosclerosis. 2015; 242(1):141-4. DOI: 10.1016/j.atherosclerosis.2015.05.005. View

Hold G, Smith M, Grange C, Watt E, El-Omar E, Mukhopadhya I . Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years?. World J Gastroenterol. 2014; 20(5):1192-210. PMC: 3921503. DOI: 10.3748/wjg.v20.i5.1192. View

Busby M, Fischer L, da Costa K, Thompson D, Mar M, Zeisel S . Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria. J Am Diet Assoc. 2004; 104(12):1836-45. DOI: 10.1016/j.jada.2004.09.027. View

Jalandra R, Dalal N, Yadav A, Verma D, Sharma M, Singh R . Emerging role of trimethylamine-N-oxide (TMAO) in colorectal cancer. Appl Microbiol Biotechnol. 2021; 105(20):7651-7660. DOI: 10.1007/s00253-021-11582-7. View

Tang W, Wang Z, Li X, Fan Y, Li D, Wu Y . Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus. Clin Chem. 2016; 63(1):297-306. PMC: 5659115. DOI: 10.1373/clinchem.2016.263640. View

Wu M, Yang S, Wang S, Cao Y, Zhao R, Li X . Effect of Berberine on Atherosclerosis and Gut Microbiota Modulation and Their Correlation in High-Fat Diet-Fed ApoE-/- Mice. Front Pharmacol. 2020; 11:223. PMC: 7083141. DOI: 10.3389/fphar.2020.00223. View

Sawicka A, Renzi G, Olek R . The bright and the dark sides of L-carnitine supplementation: a systematic review. J Int Soc Sports Nutr. 2020; 17(1):49. PMC: 7507632. DOI: 10.1186/s12970-020-00377-2. View

10.

McEntyre C, Lever M, Chambers S, George P, Slow S, Elmslie J . 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. 2014; 52(Pt 3):352-60. DOI: 10.1177/0004563214545346. View

11.

Hamaker B, Tuncil Y . A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota. J Mol Biol. 2014; 426(23):3838-50. DOI: 10.1016/j.jmb.2014.07.028. View

12.

Rogerson D . Vegan diets: practical advice for athletes and exercisers. J Int Soc Sports Nutr. 2017; 14:36. PMC: 5598028. DOI: 10.1186/s12970-017-0192-9. View

13.

Jung C, Heinze T, Schnackenberg L, Mullis L, Elkins S, Elkins C . Interaction of dietary resveratrol with animal-associated bacteria. FEMS Microbiol Lett. 2009; 297(2):266-73. DOI: 10.1111/j.1574-6968.2009.01691.x. View

14.

Chen H, Li J, Li N, Liu H, Tang J . Increased circulating trimethylamine N-oxide plays a contributory role in the development of endothelial dysfunction and hypertension in the RUPP rat model of preeclampsia. Hypertens Pregnancy. 2019; 38(2):96-104. DOI: 10.1080/10641955.2019.1584630. View

15.

Martin F, Wang Y, Sprenger N, Yap I, Lundstedt T, Lek P . Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. Mol Syst Biol. 2008; 4:157. PMC: 2238715. DOI: 10.1038/msb4100190. View

16.

Wu L, Wu J . Hyperhomocysteinemia is a risk factor for cancer and a new potential tumor marker. Clin Chim Acta. 2002; 322(1-2):21-8. DOI: 10.1016/s0009-8981(02)00174-2. View

17.

Sze M, Baxter N, Ruffin 4th M, Rogers M, Schloss P . Normalization of the microbiota in patients after treatment for colonic lesions. Microbiome. 2017; 5(1):150. PMC: 5689185. DOI: 10.1186/s40168-017-0366-3. View

18.

Zaina S, Lindholm M, Lund G . Nutrition and aberrant DNA methylation patterns in atherosclerosis: more than just hyperhomocysteinemia?. J Nutr. 2004; 135(1):5-8. DOI: 10.1093/jn/135.1.5. View

19.

Vallance H, Koochin A, Branov J, Rosen-Heath A, Bosdet T, Wang Z . Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral l-carnitine. Mol Genet Metab Rep. 2018; 15:130-133. PMC: 6047224. DOI: 10.1016/j.ymgmr.2018.04.005. View

20.

Donato A, Morgan R, Walker A, Lesniewski L . Cellular and molecular biology of aging endothelial cells. J Mol Cell Cardiol. 2015; 89(Pt B):122-35. PMC: 4522407. DOI: 10.1016/j.yjmcc.2015.01.021. View