The origin of trimethylamine-
            <i>N</i>-oxide (TMAO) and its role in development of atherosclerosis

He, Zouyan; Chen, Zhenyu

doi:10.31665/jfb.2018.2138

Cited by 8 publications

(11 citation statements)

References 79 publications

(125 reference statements)

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“…TMA is subsequently metabolized by flavin monooxygenases (FMOs), a liver phase I enzyme, to TMAO (Liu et al 2015) ( Figure 1). Marine fish is another notable dietary source of TMAO (He and Chen 2018). TMAO serves as an osmoregulatory compound in marine fish, particularly gadoids, and serves as a source of TMA and dimethylamine (DMA) formation in such fish after harvest (Parkin and Hultin 1982).…”

Section: Biosynthesis Of Trimethylamine-n-oxide (Tmao)mentioning

confidence: 99%

“…However, there are many possible and undesirable side effects of antibiotics and the considerations of antibiotic resistance in bacteria. Diet and nutritional interventions based on the use of natural bioactive compounds may offer one of the possibilities for remodeling gut microbiota composition and improving human health (Banikazemi et al 2018;He and Chen 2018).…”

Section: Natural Compounds In Tmao Researchmentioning

confidence: 99%

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Potential effects of natural dietary compounds on trimethylamine N-oxide (TMAO) formation and TMAO-induced atherosclerosis

Chen¹,

Ho²,

Shahidi³

et al. 2018

Journal of Food Bioactives

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Cardiovascular disease (CVD) is the leading cause of death worldwide. Recently, trimethylamine N-oxide (TMAO) is identified to be highly associated with CVD development and exacerbates atherosclerosis by several mechanisms. TMAO is a gut microbiota-dependent metabolite formed from dietary quaternary amines, mainly choline and carnitine. These trimethylamine (TMA)-containing compounds are first converted to TMA by enzymes in gut microbiota and subsequently metabolized by the host hepatic enzymes to TMAO. As the microbiome is the source of TMAO, administration of broad spectrum antibiotics shows marked decrease in TMAO levels. However, antibiotics may possess many possible undesirable side effects and chronic treatment consideration effects of antibiotic resistance in bacteria. Thus, studies have focused on the alternative strategies, including use of natural dietary compounds to reduce elevated TMAO levels and prevent atherogenesis. Natural dietary compounds have been studied for their beneficial health effects for decades. Diet and nutritional interventions based on the use of natural bioactive compounds is an effective strategy for remodeling gut microbiota composition and improving human health. This review focuses on the mechanisms by which TMAO promote atherosclerosis, the microbes that contribute to TMA formation, the enzymes involved, and the potential of natural dietary compounds that contribute to TMAO reduction and attenuate TMAO-induced atherosclerosis.

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Section: Biosynthesis Of Trimethylamine-n-oxide (Tmao)mentioning

confidence: 99%

Section: Natural Compounds In Tmao Researchmentioning

confidence: 99%

Potential effects of natural dietary compounds on trimethylamine N-oxide (TMAO) formation and TMAO-induced atherosclerosis

Chen¹,

Ho²,

Shahidi³

et al. 2018

Journal of Food Bioactives

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“…Trimethylamine-N-oxide (TMAO), a potential diet-derived and gut microbiota (GMB)-dependent metabolite, has been associated with an increased risk of cardiovascular disease (CVD) independent of traditional risk factors in numerous population studies [1][2][3]. Environmental and host factors, such as GMB, dietary intake, and host genetics, are thought to independently and jointly in uence circulating levels of TMAO [4], but data from human population studies are still limited. Identifying potential drivers for alternations in circulating TMAO may have preventive and therapeutic implications in CVD.…”

Section: Introductionmentioning

confidence: 99%

“…Dietary trimethylamine (TMA)-containing nutrients, including choline, phosphatidylcholine, carnitine, and betaine abundant in animal foods such as red meat (e.g., beef and pork) and eggs [1,5], can be converted to TMAO in humans through a series of physiological processes 2 . Speci cally, TMA is liberated from TMA-containing nutrients by intestinal bacteria [4], passively absorbed into the circulation system and then oxidized to TMAO by avin monooxygenases in the liver [1]. In addition to TMAO produced from dietary precursors, preformed TMAO in humans [6] and animals [7] can be absorbed in a manner not involving gut microbes.…”

Section: Introductionmentioning

confidence: 99%

Dietary factors, gut microbiota, and serum trimethylamine-N-oxide associated with cardiovascular disease

Mei¹,

Chen²,

Wang³

et al. 2020

Preprint

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Background Trimethylamine-N-oxide (TMAO), a diet-derived and gut microbiota-related metabolite, is associated with cardiovascular disease (CVD). However, the major dietary determinants and the specific gut bacterial taxa related to TMAO remain to be identified in humans. We aimed to identify dietary and gut microbial factors independently and jointly associated with circulating TMAO. Results We examined usual dietary intake, fecal gut microbiome profiled by shotgun metagenomics, and their interactions in relation to serum TMAO and its precursors among up to 3972 adult participants from the Hispanic Community Health Study/Study of Latinos. We confirmed the positive association between TMAO and prevalent CVD (OR = 1.28, P = 4.36⋅10− 4). Fish (P = 1.26⋅10− 17), red meat (P = 3.33⋅10− 16), and egg (P = 3.89⋅10− 5) intakes were top dietary factors positively associated with serum TMAO independently of each other. Red meat and egg intakes, but not fish intake, were positively associated with serum TMAO precursors (e.g., carnitine, choline). We identified 9 gut bacterial species significantly associated with serum TMAO after multiple testing correction (FDR < 0.05). All 4 TMAO-positively-associated bacteria belong to the Clostridiales order, 3 of which may have homologous genes encoding carnitine monooxygenase, an enzyme converting carnitine to trimethylamine (TMA)/TMAO. The red meat-TMAO association was more pronounced for participants with higher abundance of these 4 bacterial species than those with lower abundance (Pinteraction=0.013), but such microbial modification was not observed for fish-TMAO or egg-TMAO associations. Conclusion In US Hispanics/Latinos, fish, red meat, and egg intakes are major dietary factors associated with serum TMAO. The identified potential TMA-producing gut microbiota and microbial modification on the red meat-TMAO association support microbial TMA/TMAO production from dietary carnitine, while the fish-TMAO association is independent of gut microbiota.

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“…L-Carnitine is metabolized by intestinal microbiota to release trimethylamine (TMA), which is then absorbed by the gut into portal circulation and rapidly oxidized by hepatic flavin monooxygenases (FMO) in the liver to form trimethylamine oxide (TMAO) and subsequently released to the blood system. TMAO in blood induces oxidative stress and vascular inflammation, attacks vascular cells and causes vascular diseases such as atherosclerosis (He and Chen, 2018;Koeth et al, 2013;Micha et al, 2010). A citrus peel phytochemical, nobiletin (5,6,7,8,3′,Nob), was identi-fied as an inhibitor of both nitic oxide (NO) and superoxide (O 2 − ) generation in inflammation-associated tumorigenesis (Murakami et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Nobiletin prevents TMAO-induced vascular oxidative stress in rats

Yang¹,

Lin²,

Li³

et al. 2019

Journal of Food Bioactives

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Choline-rich foods in the diet are metabolized by intestinal microflora to trimethylamine (TMA). TMA is subsequently oxidized in the liver by hepatic flavin monooxygenases (FMO), yielding trimethylamine oxide (TMAO) in vivo. TMAO has been reported to cause blood vessel inflammation and induce vascular diseases and atherosclerosis. To investigate the preventive effect of nobiletin on choline chloride-induced vascular oxidative stress and inflammation, the choline chloride-treated rats were intragastric administrated of nobiletin. The serum content of IL-1β, MCP-1, IL-6 and TNF-α were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA), and the contents of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) were measured. The results revealed that nobiletin decreased the oxidative stress of the aorta and serum inflammatory cytokines level of the experimental rats to reduce the level of vascular inflammation.

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The origin of trimethylamine- N-oxide (TMAO) and its role in development of atherosclerosis

Cited by 8 publications

References 79 publications

Potential effects of natural dietary compounds on trimethylamine N-oxide (TMAO) formation and TMAO-induced atherosclerosis

Potential effects of natural dietary compounds on trimethylamine N-oxide (TMAO) formation and TMAO-induced atherosclerosis

Dietary factors, gut microbiota, and serum trimethylamine-N-oxide associated with cardiovascular disease

Nobiletin prevents TMAO-induced vascular oxidative stress in rats

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