• bile acid
• immunity
• metabolism
• whole body

• Bile Acids and Salts/metabolism
• Humans
• Homeostasis
• Signal Transduction
• Animals
• Liver/metabolism
• Lipid Metabolism
• Immune System/metabolism

• PAGln
• biomarker
• cardiovascular disease
• gut microbiota
• uremic metabolite

• Humans
• Cardiovascular Diseases
• Gastrointestinal Microbiome
• Thrombosis
• Glutamine/analogs & derivatives

• acute coronary syndrome
• cardiovascular disease
• lipidomics
• metabolomics
• microbiome

• Humans
• Gastrointestinal Microbiome
• Acute Coronary Syndrome
• Angina, Stable
• Lipopolysaccharide Receptors
• Metabolomics
• Bacteria

• NT-proBNP
• PAGln
• biomarker
• heart failure
• β-blocker

• Humans
• Stroke Volume/physiology
• Heart Failure
• Biomarkers
• Prognosis
• Peptide Fragments
• Natriuretic Peptide, Brain

• gut microbiota
• inflammation
• melatonin
• pulmonary hypertension
• signaling pathways

• South African Medical Research Council
• Harry Crossley Foundation

Increasing researches have considered gut microbiota as a new “metabolic organ,” which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.

• National Natural Science Foundation of China
• Natural Science Foundation of Beijing Municipality

A healthy gut provides the perfect habitat for trillions of bacteria, called the intestinal microbiota, which is greatly responsive to the long-term diet; it exists in a symbiotic relationship with the host and provides circulating metabolites, hormones, and cytokines necessary for human metabolism. The gut–heart axis is a novel emerging concept based on the accumulating evidence that a perturbed gut microbiota, called dysbiosis, plays a role as a risk factor in the pathogenesis of cardiovascular disease. Consequently, recovery of the gut microbiota composition and function could represent a potential new avenue for improving patient outcomes. Despite their low absorption, preclinical evidence indicates that polyphenols and their metabolites are transformed by intestinal bacteria and halt detrimental microbes’ colonization in the host. Moreover, their metabolites are potentially effective in human health due to antioxidant, anti-inflammatory, and anti-cancer effects. The aim of this review is to provide an overview of the causal role of gut dysbiosis in the pathogenesis of atherosclerosis, hypertension, and heart failure; to discuss the beneficial effects of polyphenols on the intestinal microbiota, and to hypothesize polyphenols or their derivatives as an opportunity to prevent and treat cardiovascular diseases by shaping gut eubiosis.

Relentless human curiosity to understand the basis of every aspect of medical science has led humanity to unlock the deepest secrets about the physiology of human existence and, in the process, has reached milestones that a century ago could only be imagined. Recent ground-breaking breakthroughs have helped scientists and physicians all over the world to update the scientific basis of diseases and hence further improve treatment outcomes. According to recent studies, scientists have found a link between intestinal flora and the pathogenesis of diseases, including cardiovascular diseases. Any change in the typical habitat of gut microbiota has been shown to result in the culmination of various metabolic and cardiac diseases. Therefore, gut microbiota can be credited for influencing the course of the development of a disease. Any change in the composition and function of bacterial species living in the gut can result in both beneficial and harmful effects on the body. Gut microbiota achieves this role by numerous mechanisms. Generations of various metabolites like TMAO (trimethylamine N-oxide), increased receptibility of various bacterial antigens, and disruption of the enzyme action in various metabolic pathways like the bile acids pathway may result in the development of metabolic as well as cardiovascular diseases. Even if they may not be the only etiological factor in the pathogenesis of a disease, they may very well serve as a contributing factor in worsening the outcome of the condition. Studies have shown that they actively play a role in the progression of cardiovascular diseases like atherosclerotic plaque formation and rising blood pressure. The focus of this review article is to establish a relation between various cardiovascular diseases and gut microbiota. This could prove beneficial for clinicians, health care providers, and scientists to develop novel therapeutic algorithms while treating cardiac patients.

Bile acids are specific and quantitatively important organic components of bile, which are synthesized by hepatocytes from cholesterol and are involved in the osmotic process that ensures the outflow of bile. Bile acids include many varieties of amphipathic acid steroids. These are molecules that play a major role in the digestion of fats and the intestinal absorption of hydrophobic compounds and are also involved in the regulation of many functions of the liver, cholangiocytes, and extrahepatic tissues, acting essentially as hormones. The biological effects are realized through variable membrane or nuclear receptors. Hepatic synthesis, intestinal modifications, intestinal peristalsis and permeability, and receptor activity can affect the quantitative and qualitative bile acids composition significantly leading to extrahepatic pathologies. The complexity of bile acids receptors and the effects of cross-activations makes interpretation of the results of the studies rather difficult. In spite, this is a very perspective direction for pharmacology.

• bile acids
• bile acids receptors
• pathogenesis

• Bile
• Bile Acids and Salts
• Hepatocytes
• Human Body
• Humans
• Liver/physiology

• Acute ischemic stroke
• In-hospital complication
• Mortality
• Stroke severity
• Total bile acids

• Aged
• Bile Acids and Salts/blood
• Female
• Humans
• Ischemic Stroke/blood
• Ischemic Stroke/diagnosis
• Ischemic Stroke/mortality
• Male
• Middle Aged
• Patient Acuity
• Prognosis
• Risk Factors

The lipid deposition and health status of egg-laying hens is crucial to the development of the poultry industry. This study aimed to evaluate the effects of genetic variations in the flavin-containing monooxygenase 3 (FMO3) on the lipid metabolic diseases of laying hens during the late laying period. The results showed that the T329S mutation in FMO3 moderated the lipid parameters and decreased the atherosclerotic lesions and hepatic steatosis in laying hens with homozygous T329S mutation. In conclusion, the T329S mutation in FMO3 is closely associated with the improvement of lipid metabolic diseases in laying hens during the late laying period. The results of this study may contribute to overcoming the challenge of lipid metabolic diseases in laying hens during the late laying period.

The T329S mutation in flavin-containing monooxygenase 3 (FMO3) impairs the trimethylamine (TMA) metabolism in laying hens. The TMA metabolic pathway is closely linked to lipid metabolic diseases, such as atherosclerosis and fatty liver disease. We aimed to evaluate the effects of the T329S mutation in FMO3 on lipid metabolism in chickens during the late laying period. We selected 18 FMO3 genotyped individuals (consisting of six AA, six AT, and six TT hens) with similar body weight and production performance. The lipid metabolism and deposition characteristics of the laying hens with different genotypes were compared. The T329S mutation moderated the serum-lipid parameters in TT hens compared to those in AA and AT hens from 49 to 62 weeks. Furthermore, it reduced the serum trimethylamine N-oxide concentrations and increased the serum total bile acid (p < 0.05) and related lipid transporter levels in TT hens. Moreover, it significantly (p < 0.01) decreased atherosclerotic lesions and hepatic steatosis in TT hens compared to those in the AA and AT hens. Our findings may help improve the health status in laying hens during the late laying period.

• chicken
• flavin-containing monooxygenase 3
• health status
• lipid metabolic disease
• mutation

Synthetized by the liver and metabolized by the gut microbiota, BA are involved in metabolic liver diseases that are associated with cardiovascular disorders. Animal models of atheroma documented a powerful anti-atherosclerotic effect of bile acids (BA). This prospective study examined whether variations in circulating BA are predictive of coronary artery disease (CAD) in human. Consecutive patients undergoing coronary angiography were enrolled. Circulating and fecal BA were measured by high pressure liquid chromatography and tandem mass spectrometry. Of 406 screened patients, 80 were prospectively included and divided in two groups with (n = 45) and without (n = 35) CAD. The mean serum concentration of total BA was twice lower in patients with, versus without CAD (P = 0.005). Adjusted for gender and age, this decrease was an independent predictor of CAD. In a subgroup of 17 patients, statin therapy doubled the serum BA concentration. Decreased serum concentrations of BA were predictors of CAD in humans. A subgroup analysis showed a possible correction by statins. With respect to the anti-atherosclerotic effect of BA in animal models, and their role in human lipid metabolism, this study describe a new metabolic disturbance associated to CAD in human.

• Atherosclerosis
• Cardiomyocytes
• Cardiomyopathy
• Mechanism.
• Metabolites
• Signalling pathway
• Trimethylamine N-oxide

Bile acids (BAs) are classically known to play a vital role in the metabolism of lipids and in absorption. It is now well established that BAs act as signaling molecules, activating different receptors (such as farnesoid X receptor, vitamin D receptor, Takeda G-protein-coupled receptor 5, sphingosine-1-phosphate, muscarinic receptors, and big potassium channels) and participating in the regulation of energy homeostasis and lipid and glucose metabolism. In addition, increased BAs can impair cardiovascular function in liver cirrhosis. Approximately 50% of patients with cirrhosis develop cirrhotic cardiomyopathy. Exposure to high concentrations of hydrophobic BAs has been shown to be related to adverse effects with respect to vascular tension, endothelial function, arrhythmias, coronary atherosclerotic heart disease, and heart failure. The BAs in the serum BA pool have relevant through their hydrophobicity, and the lipophilic BAs are more harmful to the heart. Interestingly, ursodeoxycholic acid is a hydrophilic BA, and it is used as a therapeutic drug to reverse and protect the harmful cardiac effects caused by hydrophobic elevated BAs. In order to elucidate the mechanism of BAs and cardiovascular function, abundant experiments have been conducted in vitro and in vivo. The aim of this review was to explore the mechanism of BAs in the cardiovascular system.

• Bile acids
• Cardiovascular
• Arteries
• Receptors
• Signaling
• Cirrhosis

Since the discovery of the potential role for the gut microbiota in health and disease, many studies have gone on to report its impact in various pathologies. These studies have fuelled interest in the microbiome as a potential new target for treating disease Here, we reviewed the key metabolic diseases, obesity, type 2 diabetes and atherosclerosis and the role of the microbiome in their pathogenesis. In particular, we will discuss disease associated microbial dysbiosis; the shift in the microbiome caused by medical interventions and the altered metabolite levels between diseases and interventions. The microbial dysbiosis seen was compared between diseases including Crohn’s disease and ulcerative colitis, non-alcoholic fatty liver disease, liver cirrhosis and neurodegenerative diseases, Alzheimer’s and Parkinson’s. This review highlights the commonalities and differences in dysbiosis of the gut between diseases, along with metabolite levels in metabolic disease vs. the levels reported after an intervention. We identify the need for further analysis using systems biology approaches and discuss the potential need for treatments to consider their impact on the microbiome.

• dysbiosis
• gut microbiota
• metabolic diseases
• metagenomics
• systems biology

The slow coronary flow (SCF) phenomenon was characterized by delayed perfusion of epicardial arteries, and no obvious coronary artery lesion in coronary angiography. The prognosis of patients with slow coronary flow was poor. However, there is lack of rapid, simple, and accurate method for SCF diagnosis. This study aimed to explore the utility of plasma choline as a diagnostic biomarker for SCF.

Patients with coronary artery stenosis <40% evaluated by the coronary angiogram method were recruited in this study and were grouped into normal coronary flow (NCF) and SCF by thrombolysis in myocardial infarction frame count (TFC). Plasma choline concentrations of patients with NCF and SCF were quantified by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry. Correlation analysis was performed between plasma choline concentration and TFC. Receiver operating characteristic (ROC) curve analysis with or without confounding factor adjustment was applied to predict the diagnostic power of plasma choline in SCF.

Forty-four patients with SCF and 21 patients with NCF were included in this study. TFC in LAD, LCX, and RCA and mean TFC were significantly higher in patients with SCF in comparison with patients with NCF (32.67 ± 8.37 vs. 20.66 ± 3.41, P  <  0.01). Plasma choline level was obviously higher in patients with SCF when compared with patients with NCF (754.65 ± 238.18 vs. 635.79 ± 108.25, P=0.007). Plasma choline level had significantly positive correlation with Mean TFC (r = 0.364, P=0.002). Receiver operating characteristic (ROC) analysis showed that choline with or without confounding factor adjustment had an AUC score of 0.65 and 0.77, respectively.

TFC were closely related with plasma choline level, and plasma choline can be a suitable and stable diagnostic biomarker for SCF.

• Circulating bile acid
• atherosclerosis
• coronary computed tomography angiography (CTA)
• plaque

• coronary artery disease
• heart failure
• hypertension
• intestinal microbiota

Recent evidence, including massive gene-expression analysis and a wide-variety of other multi-omics approaches, demonstrates an interplay between gut microbiota and the regulation of plasma lipids. Gut microbial metabolism of choline and l-carnitine results in the formation of trimethylamine (TMA) and concomitant conversion into trimethylamine-N-oxide (TMAO) by liver flavin monooxygenase 3 (FMO3). The plasma level of TMAO is determined by the genetic variation, diet and composition of gut microbiota. Multiple studies have demonstrated an association between TMAO plasma levels and the risk of atherothrombotic cardiovascular disease (CVD). We aimed to review the molecular pathways by which TMAO production and FMO3 exert their proatherogenic effects. TMAO may promote foam cell formation by upregulating macrophage scavenger receptors, deregulating enterohepatic cholesterol and bile acid metabolism and impairing macrophage reverse cholesterol transport (RCT). Furthermore, FMO3 may promote dyslipidemia by regulating multiple genes involved in hepatic lipogenesis and gluconeogenesis. FMO3 also impairs multiple aspects of cholesterol homeostasis, including transintestinal cholesterol export and macrophage-specific RCT. At least part of these FMO3-mediated effects on lipid metabolism and atherogenesis seem to be independent of the TMA/TMAO formation. Overall, these findings have the potential to open a new era for the therapeutic manipulation of the gut microbiota to improve CVD risk.

• FMO3
• atherosclerosis and cardiovascular disease
• cholesterol homeostasis
• intestinal microbiota
• reverse cholesterol transport
• trimethylamine
• trimethylamine-N-oxide

• Animals
• Cholesterol/metabolism
• Gastrointestinal Microbiome
• Gluconeogenesis/genetics
• Humans
• Lipogenesis/genetics
• Liver/metabolism
• Metabolic Syndrome/genetics
• Metabolic Syndrome/metabolism
• Methylamines/metabolism

• antibiotics
• cardiovascular disease
• gut dysbiosis
• inflammation
• microbiota
• neurological disorder

• cooking oils
• human feeding study
• metabolomics study

• Adult
• Cooking
• Dietary Fats/metabolism
• Fatty Acids/metabolism
• Humans
• Male
• Metabolomics
• Middle Aged
• Plant Oils/metabolism
• Postprandial Period
• Triglycerides/metabolism
• Young Adult

• Cardiovascular disease
• cardiovascular risk
• dyslipidemia
• fat
• lipid profile
• red meat

• AMP-Activated Protein Kinases/metabolism
• Acetyl-CoA Carboxylase/metabolism
• Animals
• Blood Glucose/analysis
• Dexamethasone/pharmacology
• Diet, High-Fat
• Fatty Acids, Nonesterified/pharmacology
• Fatty Liver/metabolism
• Fatty Liver/pathology
• Fatty Liver/veterinary
• Hep G2 Cells
• Humans
• Leptin/genetics
• Leptin/metabolism
• Lipid Metabolism/drug effects
• Liver/metabolism
• Liver/pathology
• Male
• Medicine, Korean Traditional
• Mice
• Mice, Inbred C57BL
• Phosphorylation/drug effects
• Plant Extracts/chemistry
• Plant Extracts/pharmacology
• Signal Transduction/drug effects

Background. 7-Alpha cholesterol hydroxylase (CYP7A1), the first enzyme of classic conversion pathway leading from cholesterol to bile acids synthesis, is encoded by CYP7A1 gene. Its single nucleotide polymorphisms (SNPs) influence serum lipid levels and may be related to impaired lipid profile leading to coronary artery disease (CAD). The aim of the present study was to analyze the possible association between the rs7833904 CYP7A1 polymorphism and premature CAD. Material and Methods. Serum lipid levels and rs7833904 SNP were determined in 419 subjects: 200 patients with premature CAD and 219 age and sex matched controls. Results. The A allele carrier state was associated with CAD (OR = 1.76, 95% CI; 1.14–2.71, P = 0.014). The effect was even stronger in the male subgroups (OR = 2.16, 95% CI; 1.28–3.65, P = 0.003). There was no effect in the females. Risk factors of CAD and clinical phenotype of atherosclerosis were not associated with genotype variants of the rs7833904 SNP. Lipid profiles also did not differ significantly between individual genotypes. Conclusion. The CYP7A1 rs7833904 polymorphism may modify the risk of CAD. This effect is especially strong in male subjects. The studied polymorphism does not significantly influence serum lipid levels, in the present study.

• Animals
• Atherosclerosis/etiology
• Atherosclerosis/microbiology
• Atherosclerosis/physiopathology
• Carnitine/chemistry
• Carnitine/metabolism
• Cholesterol/metabolism
• Choline/chemistry
• Desmosterol/metabolism
• Female
• Humans
• Intestines/microbiology
• Macrophages/metabolism
• Mass Spectrometry
• Meat
• Metagenome
• Methylamines/blood
• Methylamines/metabolism
• Mice
• Mice, Knockout
• RNA/metabolism
• Time Factors

• UL1 RR024989 NCRR NIH HHS
• P30-DK034987-25-28 NIDDK NIH HHS
• RC1 DK086472 NIDDK NIH HHS
• P20 HL113452 NHLBI NIH HHS
• 1RC1DK086472 NIDDK NIH HHS
• P40 RR018603 NCRR NIH HHS
• P01 HL098055 NHLBI NIH HHS
• P40-RR018603-06-08 NCRR NIH HHS
• P01 HL30568 NHLBI NIH HHS
• P01 H28481 PHS HHS
• R00 HL096166 NHLBI NIH HHS
• T32 GM007250 NIGMS NIH HHS
• R01 CA127334 NCI NIH HHS
• UH3 DK083981 NIDDK NIH HHS
• R01 HL103931 NHLBI NIH HHS
• R01 HL103866 NHLBI NIH HHS
• P30 DK034987 NIDDK NIH HHS
• 1UL1RR024989 NCRR NIH HHS
• UH3-DK083981 NIDDK NIH HHS
• P01 HL028481 NHLBI NIH HHS
• P01 HL076491 NHLBI NIH HHS
• R01 HL098193 NHLBI NIH HHS
• P01 HL030568 NHLBI NIH HHS