Is There any Possible Association Between Trimethylamine N-Oxide (TMAO) and Cancer? A Review Study
Adeleh khodabakhshi1*, Mohammadreza Rooholamini2
1. Assistant Prof, Dept. of Nutrition, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran.
2. Undergraduate Student, Dept. of Nutrition, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran.
* Corresponding author: Adeleh khodabakhsh; E-mail: Khodabakhshiadeleh@yahoo.com
Abstract
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.
Keywords: Trimethylamine N-oxide, Cancer, Colorectal Cancer, Trimethylamine
Introduction
Cancer is a leading cause of death worldwide. There was an estimated rate of 19.3 million new cancer cases, accounting for nearly 10 million deaths in 2020. The overall incidence rate was higher in transitioned countries than in transitioning ones in both sexes [1].
Several factors can be responsible for the incidence of cancer [2-4]. One of the factors that has recently been shown to have a relationship with cancer, along with other diseases, is an organic compound called trimethylamine N-oxide (TMAO) [5, 6]. TMAO is produced by a precursor, i.e. trimethylamine (TMA), being a metabolite of various precursors, mainly choline and carnitine from ingested foods. The increase in TMAO levels can be attributed to two sources. The first source is TMA that is derived from precursor molecules by the action of gut bacteria and subsequent oxidation in the liver. The second one is dietary intake of TMAO-rich foods, such as red meat, eggs, milk, and certain fish products, including salmons [7, 8]. High levels of serum TMAO could be associated with the risk of Cardiovascular Disease (CVD) [9-11]. Research shows that by increasing cholesterol accumulation in macrophages and in foam cells of artery walls, TMAO contributes to atherosclerosis, thereby leading to cardiovascular disease [12]. According to animal studies, elevated levels of TMAO are directly associated with progressive organ fibrosis and dysfunction [13, 14].
The TMAO pathway and its metabolites are possibly involved in the development of two major health problems, including insulin resistance and cancer [15]. There is an association between high TMAO levels with low bacterial diversity and a change in the composition and distribution of bacterial phylotypes. Thus, a change in gut microbiota contributes to oncogenesis and tumor progression, both locally and systemically. Although inflammatory and metabolic cues support this phenomenon, additional mechanisms could attribute to the ability of dysbiosis to promote carcinogenesis [16]. We firstly describe TMAO and
its formation pathways in brief. Next, we investigate the possible association that may exist between TMAO and cancer. Finally, we review recent studies on the potential correlation between TMAO and cancer.
Materials and Methods
A comprehensive review of electronic databases, including ISI web of knowledge, Scopus, and PubMed was made using the main keywords of "cancer" and "Trimethylamine N-oxide". Besides, a manual search was done in the references of the articles gathered to improve the precision of the review. There were no restrictions on the date of publication. Randomized trials, case control studies, and prospective cohort studies were included for the purpose of this study. However, we excluded reviews and studies on animals, available articles with incomplete texts, and articles irrelevant to our topic.