Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far?

Coutinho-Wolino, Karen Salve; Cardozo, Ludmila F M F; Leal, Viviane de Oliveira; Mafra, Denise; Stockler‐Pinto, Milena Barcza

doi:10.1007/s00394-021-02491-6

Cited by 68 publications

(45 citation statements)

References 134 publications

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“…TMAO is a gut-derived metabolite depending on the function of the intestinal barrier, which is associated with an increased risk of metabolic syndrome, cardiovascular disease, and mortality [ 55 ]. Besides the gut microbiota, circulating TMAO concentrations are determined by many factors, such as age, gender, and dietary nutrients [ 15 ]. We previously reported that the circulating TMAO concentrations were negatively associated with a healthy dietary pattern, such as MD and 25-OH vitamin D levels [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Trimethylamine (TMA) is the product of the metabolism of dietary nutrients commonly present in the Western diet, such as choline and carnitine, which are found in red meat, eggs, milk, and cheese [ 15 ]. TMA is further metabolized in the liver to trimethylamine N-oxide (TMAO) [ 15 ]. Despite the fact that there is a large consensus that circulating TMAO concentrations are mainly dependent on dietary patterns, a relevant contribution to the liver production of TMAO is provided by the fermentation of dietary TMA produced by gut bacteria, including Proteobacteria and Firmicutes [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the fact that there is a large consensus that circulating TMAO concentrations are mainly dependent on dietary patterns, a relevant contribution to the liver production of TMAO is provided by the fermentation of dietary TMA produced by gut bacteria, including Proteobacteria and Firmicutes [ 16 ]. Through mediating inflammatory processes, TMAO would have a potential association with most chronic non-communicable diseases, including cancer, type 2 diabetes, obesity, metabolic syndrome, nonalcoholic fatty liver disease, and Alzheimer’s disease [ 15 ]. In the case of gut dysbiosis, an increase in the microorganisms that produce TMAO has been observed, thus suggesting TMAO as one of the biomarkers for metabolite profiling and diagnostic suitability for dysbiosis [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations

Barrea

Muscogiuri²,

Pugliese³

et al. 2021

Nutrients

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Individual differences in the chronotype, an attitude that best expresses the individual circadian preference in behavioral and biological rhythms, have been associated with cardiometabolic risk and gut dysbiosis. Up to now, there are no studies evaluating the association between chronotypes and circulating TMAO concentrations, a predictor of cardiometabolic risk and a useful marker of gut dysbiosis. In this study population (147 females and 100 males), subjects with the morning chronotype had the lowest BMI and waist circumference (p < 0.001), and a better metabolic profile compared to the other chronotypes. In addition, the morning chronotype had the highest adherence to the Mediterranean diet (p < 0.001) and the lowest circulating TMAO concentrations (p < 0.001). After adjusting for BMI and adherence to the Mediterranean diet, the correlation between circulating TMAO concentrations and chronotype score was still kept (r = −0.627, p < 0.001). Using a linear regression analysis, higher chronotype scores were mostly associated with lower circulating TMAO concentrations (β = −0.479, t = −12.08, and p < 0.001). Using a restricted cubic spline analysis, we found that a chronotype score ≥59 (p < 0.001, R2 = −0.824) demonstrated a more significant inverse linear relationship with circulating TMAO concentrations compared with knots <59 (neither chronotype) and <41 (evening chronotype). The current study reported the first evidence that higher circulating TMAO concentrations were associated with the evening chronotype that, in turn, is usually linked to an unhealthy lifestyle mostly characterized by low adherence to the MD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations

Barrea

Muscogiuri²,

Pugliese³

et al. 2021

Nutrients

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“…Studies have shown that nutrients and bioactive compounds from food can modulate the gut microbiota to reduce TMAO production. 27 HFD-induced obese NLRP3-deficient mice had an altered composition of gut microbiota associated with reduced levels of TMAO and LPS, attenuated systemic inflammation, and improved lipid metabolism. 28 Given that higher levels of circulating TMAO could be associated with a higher risk of DM, 29 it is then important to develop the novel interventional strategy that manipulates the production of TMAO.…”

mentioning

confidence: 94%

Direct CCL4 Inhibition Modulates Gut Microbiota, Reduces Circulating Trimethylamine N-Oxide, and Improves Glucose and Lipid Metabolism in High-Fat-Diet-Induced Diabetes Mellitus

Chang¹,

Chen²

2021

JIR

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Purpose: Modulation of the gut microbiota may lead to changes in pathological conditions. C-C chemokine motif ligand (CCL) 4 was upregulated in diabetes mellitus (DM) and was shown to play a significant role in pancreatic inflammation and glucose metabolism. The detailed in vivo mechanisms have not been well explored. This study aimed to investigate the hypothesis that direct CCL4 inhibition could modify gut microbiota and systemic metabolism in diet-induced DM mice. Methods: C57BL/6 mice fed a high-fat diet (HFD) were used as a diet-induced DM model. CCL4 inhibition was conducted by anti-CCL4 neutralizing monoclonal antibodies. The gut microbiota was analyzed by high-throughput sequencing of the 16S rRNA. Fecal microbiota transplantation (FMT) was used to verify the effect of CCL4 deficiency on gut microbiota and the linkage between CCL4-modulated gut microbiota and HFD-induced DM. Results: CCL4 inhibition stabilized glucose homeostasis, modulated lipid parameter, and decreased inflammatory markers in HFD-induced DM mice. Moreover, CCL4 inhibition reversed HFD-induced gut dysbiosis, evidenced by the decreased abundance of family Muribaculaceae and increased abundance of family Atopobiaceae when CCL4 antibodies were administrated. CCL4 inhibition led to a decrease in circulating trimethylamine N-oxide levels, a proinflammatory metabolite from gut microbiota. Taken together, CCL4 inhibition could modify gut microbiota profiles, suppress proinflammatory metabolites, reduce systemic inflammation, improve insulin resistance, and retard the progression of hyperglycemia in HFD-induced DM. Furthermore, FMT from CCL4 knockout mice rescued the glucose homeostasis in HFD-induced DM mice. Conclusion: Our findings may not only provide a novel rationale to in vivo CCL4-based therapeutic approach in diet-induced DM but also indicate the significance of gut microbiota profile including the family Muribaculaceae and the family Atopobiaceae as a potential modifiable target for systemic metabolism.

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Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives

Hou,

Chen,

Hazeena

et al. 2024

FEBS Open Bio

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Overall diet, lifestyle choices, genetic predisposition, and other underlying health conditions may contribute to higher trimethylamine N‐oxide (TMAO) levels and increased cardiovascular risk. This review explores the potential therapeutic ability of RSV to protect against cardiovascular diseases (CVD) and affect TMAO levels. This review considers recent studies on the association of TMAO with CVD. It also examines the sources, mechanisms, and metabolism of TMAO along with TMAO‐induced cardiovascular events. Plant polyphenolic compounds, including resveratrol (RSV), and their cardioprotective mechanism of regulating TMAO levels and modifying gut microbiota are also discussed here. RSV's salient features and bioactive properties in reducing CVD have been evaluated. The close relationship between TMAO and CVD is clearly understood from currently available data, making it a potent biomarker for CVD. Precise investigation, including clinical trials, must be performed to understand RSV's mechanism, dose, effects, and derivatives as a cardioprotectant agent.

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Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far?

Cited by 68 publications

References 134 publications

Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations

Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations

Direct CCL4 Inhibition Modulates Gut Microbiota, Reduces Circulating Trimethylamine N-Oxide, and Improves Glucose and Lipid Metabolism in High-Fat-Diet-Induced Diabetes Mellitus

Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives

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