Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function

Canyelles, Marina; Tondo, Mireia; Cedó, Lídia; Farràs, Marta; Escolà‐Gil, Joan Carles; Blanco‐Vaca, Francisco

doi:10.3390/ijms19103228

Cited by 146 publications

(138 citation statements)

References 94 publications

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“…This may be explained in part by the short time elapsed between the intake of TMAO-rich food (such as fish) or its dietary precursors (choline and carnitine found in meat and eggs), and the appearance of the metabolite in plasma, as reported by Cho et al 52 . As suggested by other authors 53 , high inter-variation in TMAO plasma levels, may be attributed to differences in gut microbiota composition and function. Some families of bacteria from Firmicutes and Proteobacteria phyla are potent choline and carnitine consumers, and are able to synthetize TMA through the expression of specific enzymes.…”

Section: Tmao In Plasma No Significant Differences In Fasting Tmao Csupporting

confidence: 55%

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study

Calderón-Pérez

Gosalbes

Yuste

et al. 2020

Sci Rep

140

115

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Hypertension is an independent and preventable risk factor for the development of cardiovascular diseases, however, little is known about the impact of gut microbiota composition in its development. We carried out comprehensive gut microbiota analysis and targeted metabolomics in a cross-sectional study of 29 non-treated hypertensive (HT) and 32 normotensive (NT) subjects. We determined fecal microbiota composition by 16S rRNA gene sequencing and bacterial functions by metagenomic analysis. The microbial metabolites analysed were short chain fatty acids (SCFA) both in plasma and feces, and trimethylamine N-oxide (TMAO) in plasma. The overall bacterial composition and diversity of bacterial community in the two groups were not significantly different. However, Ruminococcaceae NK4A214, Ruminococcaceae_UCG-010, Christensenellaceae_R-7, Faecalibacterium prausnitzii and Roseburia hominis were found to be significantly enriched in NT group, whereas, Bacteroides coprocola, Bacteroides plebeius and genera of Lachnospiraceae were increased in HT patients. We found a positive correlation between the HT-associated species and systolic and diastolic blood pressure after adjusted for measured confounders. SCFA showed antagonistic results in plasma and feces, detecting in HT subjects significant higher levels in feces and lower levels in plasma, which could indicate a less efficient SCFA absorption. Overall, our results present a disease classifier based on microbiota and bacterial metabolites to discriminate HT individuals from NT controls in a first disease grade prior to drug treatment.Hypertension is one of the leading risk factors for the development of cardiovascular diseases (CVD) globally, and lifestyle measures are effective as a preventive strategies 1 . In 2015, hypertension based on office blood pressure (BP) reported the highest rates with a global prevalence of 1.13 billion cases, and 150 million in central and eastern Europe regardless of the income countries status 2-4 .The identification of the determinants of hypertension is still challenging although it is well recognized its multifactorial etiology 5 . It has been elucidated the interplay of genetic and environmental factors related with risk-conferring behaviors, such as, smoking, lack of physical activity, alcohol consumption and unhealthy diet 6,7 .Recently, it has been evidenced the role of gut microbiota dysbiosis on the modulation of high BP, both in animal and human hypertension 8 . Mell et al. (2015) were the first to demonstrate the differential fecal microbial composition of Dahl salt-sensitive and Dahl salt-resistant rats 9 . In the same period, Yang et al. (2015) also found a clear gut dysbiosis in spontaneously hypertensive rats (SHR) mediated by a decrease in microbial richness and open Scientific RepoRtS | (2020) 10:6436 | https://doi.org/10.1038/s41598-020-63475-w www.nature.com/scientificreports www.nature.com/scientificreports/ Scientific RepoRtS | (2020) 10:6436 | https://doi.org/10.1038/s41598-020-63475-w www.nature.com/scientificreports...

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Section: Tmao In Plasma No Significant Differences In Fasting Tmao Csupporting

confidence: 55%

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study

Calderón-Pérez

Gosalbes

Yuste

et al. 2020

Sci Rep

140

115

View full text Add to dashboard Cite

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“…Changes in gut microbiota composition (to an unfavorable gut microbial environment), or gut dysbiosis, have been linked to CVD, obesity, and T2DM [11,75]. In this sense, metabolites produced by the microbiota in obese individuals can affect cardiovascular health by enhanced inflammatory response [76,77], insulin resistance [78,79], liver fat accumulation [80], and increased plasma lipid levels [81,82].…”

Section: Nut Composition and Its Implication On Body Weight And Cardimentioning

confidence: 99%

Adipokines and Adipose Tissue-Related Metabolites, Nuts and Cardiovascular Disease

Weschenfelder¹,

Quadros²,

Santos³

et al. 2020

Metabolites

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Adipose tissue is a complex structure responsible for fat storage and releasing polypeptides (adipokines) and metabolites, with systemic actions including body weight balance, appetite regulation, glucose homeostasis, and blood pressure control. Signals sent from different tissues are generated and integrated in adipose tissue; thus, there is a close connection between this endocrine organ and different organs and systems such as the gut and the cardiovascular system. It is known that functional foods, especially different nuts, may be related to a net of molecular mechanisms contributing to cardiometabolic health. Despite being energy-dense foods, nut consumption has been associated with no weight gain, weight loss, and lower risk of becoming overweight or obese. Several studies have reported beneficial effects after nut consumption on glucose control, appetite suppression, metabolites related to adipose tissue and gut microbiota, and on adipokines due to their fatty acid profile, vegetable proteins, l-arginine, dietary fibers, vitamins, minerals, and phytosterols. The aim of this review is to briefly describe possible mechanisms implicated in weight homeostasis related to different nuts, as well as studies that have evaluated the effects of nut consumption on adipokines and metabolites related to adipose tissue and gut microbiota in animal models, healthy individuals, and primary and secondary cardiovascular prevention.

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“…A recent study reported that TMAO down-regulated intestinal and liver cholesterol as well as bile acid metabolism and impaired macrophage reverse cholesterol transport. TMAO can also contribute to dyslipidemia by regulating hepatic lipogenesis and gluconeogenesis [181]. Therefore, increased systemic circulation of TMAO is associated with intestinal dysbiosis, insulin resistance, hypertriglyceridemia, hepatic steatosis, NAFLD, and cancer [182][183][184].…”

Section: Systemic Circulation Related To the Microbiota-gut-liver Axismentioning

confidence: 99%

Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis

2020

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Gut microbiota play an important role in maintaining intestinal health and are involved in the metabolism of carbohydrates, lipids, and amino acids. Recent studies have shown that the central nervous system (CNS) and enteric nervous system (ENS) can interact with gut microbiota to regulate nutrient metabolism. The vagal nerve system communicates between the CNS and ENS to control gastrointestinal tract functions and feeding behavior. Vagal afferent neurons also express receptors for gut peptides that are secreted from enteroendocrine cells (EECs), such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and 5-hydroxytryptamine (5-HT; serotonin). Gut microbiota can regulate levels of these gut peptides to influence the vagal afferent pathway and thus regulate intestinal metabolism via the microbiota-gut-brain axis. In addition, bile acids, short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and Immunoglobulin A (IgA) can also exert metabolic control through the microbiota-gut-liver axis. This review is mainly focused on the role of gut microbiota in neuroendocrine regulation of nutrient metabolism via the microbiota-gut-brain-liver axis.2 of 21 formate, acetate, propionate, and butyrate, which are related to maintaining intestinal epithelium and permeability [11]. Further, SCFAs regulate glucose and lipid metabolism as well as immune and inflammatory responses [12,13]. Hence, gut microbiota also plays an important role in immune systems, inflammation, and cancer prevention of the host [14,15]. The enteric nervous system (ENS) is reported to be involved in intestinal metabolic regulation, and enteric neurons and intestinal neurotransmitters play an important role in ENS regulation [16][17][18]. The gut contains full ENS reflex circuits, such as motor neurons, interneurons, and sensory neurons, and these neurons transfer information between the ENS and central nervous system (CNS). The vagal nerve pathway communicates between the CNS and ENS, which has remarkable impact on regulating gastrointestinal tract functions and feeding behavior [19,20]. Thus, the vagal nerve system is also involved in intestinal metabolic regulation through the gut-brain axis. Vagal afferent neurons express receptors for gut peptides, such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), 5-hydroxytryptamine (5-HT) and so on, which are secreted from enteroendocrine cells (EECs) [20][21][22]. When vagal afferent neurons sense these types of gut peptides, the corresponding gut information will transfer to the CNS and exert various reactions. At the same time, gut microbiota can regulate these gut peptides, such as CCK, ghrelin, leptin, PYY, GLP-1, 5-HT levels to influence vagal afferent pathway, and then regulated intestinal metabolic metabolism via the microbiota-gut-brain axis [23][24][25].The importance of the gut-brain axis in human health and disease has been known for a long period. However, it has only been re...

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Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function

Cited by 146 publications

References 94 publications

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study

Adipokines and Adipose Tissue-Related Metabolites, Nuts and Cardiovascular Disease

Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis

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