scholarly journals Potential effects of natural dietary compounds on trimethylamine Noxide (TMAO) formation and TMAO-induced atherosclerosis

2018 ◽  
Vol 3 ◽  
pp. 87-94
Author(s):  
Pei-Yu F. Chen ◽  
Chi-Tang Ho ◽  
Fereidoon Shahidi ◽  
Min-Hsiung Pan

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.

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 79 ◽  
Author(s):  
Marco Busnelli ◽  
Stefano Manzini ◽  
Giulia Chiesa

It is widely recognized that the microorganisms inhabiting our gastrointestinal tract—the gut microbiota—deeply affect the pathophysiology of the host. Gut microbiota composition is mostly modulated by diet, and gut microorganisms communicate with the different organs and tissues of the human host by synthesizing hormones and regulating their release. Herein, we will provide an updated review on the most important classes of gut microbiota-derived hormones and their sensing by host receptors, critically discussing their impact on host physiology. Additionally, the debated interplay between microbial hormones and the development of cardiovascular disease will be thoroughly analysed and discussed.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xin Wang ◽  
Xueqi Li ◽  
Yumei Dong

As a metabolite generated by gut microbiota, trimethylamine-N-oxide (TMAO) has been proven to promote atherosclerosis and is a novel potential risk factor for cardiovascular disease (CVD). The objective of this study was to examine whether regulating gut microbiota by vitamin D supplementation could reduce the plasma TMAO level in mice. For 16 weeks, C57BL/6J mice were fed a chow (C) or high-choline diet (HC) without or with supplementation of vitamin D3 (CD3 and HCD3) or a high-choline diet with vitamin D3 supplementation and antibiotics (HCD3A). The results indicate that the HC group exhibited higher plasma trimethylamine (TMA) and TMAO levels, lower richness of gut microbiota, and significantly increased Firmicutes and decreased Bacteroidetes as compared with group C. Vitamin D supplementation significantly reduced plasma TMA and TMAO levels in mice fed a high-choline diet. Furthermore, gut microbiota composition was regulated, and the Firmicutes/Bacteroidetes ratio was reduced by vitamin D. Spearman correlation analysis indicated that Bacteroides and Akkermansia were negatively correlated with plasma TMAO in the HC and HCD3 groups. Our study provides a novel avenue for the prevention and treatment of CVD with vitamin D.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1572-1572
Author(s):  
Ying Cheng Lin ◽  
Wei-Kai Wu ◽  
Suraphan Panyod ◽  
Ming-Shiang Wu ◽  
Lee-Yan Sheen

Abstract Objectives High consumption of red meat can lead to cardiovascular disease. L-carnitine is rich in red meat can be metabolized by gut microbiota and hepatic enzyme to produce trimethylamine N-oxide (TMAO), which is the risk factor for cardiovascular disease. Garlic is a traditional food, exhibiting a medicinal effect against many diseases as well as garlic essential oil (GEO) possess anti-oxidation, anti-inflammation, and anti-hyperlipidemic effects to prevent cardiovascular disease. The purpose of this study is to investigate the protective effects of GEO on cardiovascular disease as well as explore the mechanism via modulation of gut microbiota composition and ameliorating lipid profiles. Methods GEO was extracted by steam distillation and its chemical constituents were analyzed by gas chromatography. The eight-week-old female apoE−/− mice were randomly divided into 5 groups: (1) chow diet, (2) 1.3% carnitine in water-fed group (negative control), (3) 1.3% carnitine + GEO (25 mg/kg bw), (4) 1.3% carnitine + GEO (50 mg/kg bw), and (5) 1.3% carnitine + 1% 3,3-dimethyl-1-butanol in water-fed (positive control). The mice were gavaged with GEO or soybean oil daily after 15 weeks the mice were sacrificed. The whole aorta was collected for observing the aortic plaque formation via oil red staining. The serum cholesterol, triglyceride, HDL, AST, and ALT were measured by an automatic blood analyzer. The bacterial metabolite trimethylamine (TMA) and TMAO were examined by using LC-MS. Illumina Miseq platform was used for 16S rDNA sequencing to analyze the feces microbiota composition. Results GEO significantly reduced the atherosclerotic lesion area in aorta compared to the carnitine-fed group (P < 0.01) and the effect is better than positive control. The serum HDL was improved by GEO (P < 0.01), but no change in serum total cholesterol level. The principal coordinate analysis of feces microbial composition revealed the differences in the gut microbiota composition. The carnitine and GEO shaped the feces microbiota alpha diversity. However, there are no significant findings in bacterial metabolites. Thus, the mechanistic effect of GEO against cardiovascular disease is mainly through the modulation of serum lipidomic. Conclusions GEO can serve as a functional food to prevent cardiovascular disease risk from high intake of red meat. Funding Sources MOST 108-2321-B-002 -035.


2021 ◽  
Vol 9 (7) ◽  
pp. 1469
Author(s):  
Emanuele Rinninella ◽  
Pauline Raoul ◽  
Marco Cintoni ◽  
Marta Palombaro ◽  
Gabriele Pulcini ◽  
...  

The gut microbiome is increasingly being recognized for its influence on intestinal and extra-intestinal disorders such as cancer. Today, diet is the most studied environmental modulator of gut microbiota, capable of altering or improving it in terms of richness and diversity. Recent evidence from several preclinical and clinical trials suggested that gut microbiota composition could modulate cancer therapies (toxicities, treatment responses) and vice versa. This review highlights the latest research on the bidirectional associations between gut microbiota and cancer. We also dissect the role of gut microbiota during cancer therapies in terms of toxicity and treatment response and, in turn, how cancer therapies could impact gut microbiota composition and functions. In this context, we summarize the state-of-the-art research regarding the role of various nutritional interventions—prebiotics, dietary strategies, and dietary restrictions—as cutting-edge possibilities to modulate gut microbiota during cancer therapies.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 379-379
Author(s):  
Clara Cho ◽  
Niklas D J Aardema ◽  
Madison L Bunnell ◽  
Deanna P Larson ◽  
Sheryl S Aguilar ◽  
...  

Abstract Objectives Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. However, the contributions of different forms of choline and gut microbiota composition on TMAO production are largely unknown. The objectives of this study were to: 1) compare acute TMAO response to meals containing free choline (choline bitartrate) versus fat-soluble choline (phosphatidylcholine) and 2) to determine the effects of gut microbiota composition on TMAO response. Methods In a controlled, double-blinded, cross-over study, healthy men (n = 37) were provided meals containing (i) 600 mg choline as choline bitartrate (free choline); (ii) 600 mg choline as phosphatidylcholine; or (iii) no choline control in a random order. Blood and urine samples were collected at baseline and throughout the 6-h study period; a one-time stool sample was collected at baseline. Results Compared to no choline and phosphatidylcholine, free choline yielded 295% higher plasma TMAO (P = 0.002) and 250% higher urinary TMAO (P = 0.01), with no difference in TMAO response between phosphatidylcholine and no choline. High-TMAO producers (those with ≥40% increase in urinary TMAO response to free choline) had significantly different beta-diversity measures (unweighted UniFrac; PERMANOVA P = 0.01) compared to low-TMAO producers (those with <40% increase in TMAO response) but showed no difference in alpha-diversity. Analysis of Composition of Microbiomes (ANCOM) revealed that high-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae (in phylum Firmicutes) compared to low-TMAO producers (P < 0.05 with the strength of the ANCOM test W = 11 and W = 8, respectively). Conclusions Given that the majority of choline in food is in the form of phosphatidylcholine, the absence of TMAO elevation with phosphatidylcholine counters arguments that dietary choline should be avoided for TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiota composition may be a more appropriate strategy to reduce risk of cardiovascular disease. Funding Sources This research was supported by the Utah Agricultural Experiment Station Seed Grants Program.


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