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Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies.

ABSTRACT: Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier's Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), tryptophan and indole derivatives, with risk of cardiovascular disease (CVD). A total of twenty-one studies were included in the systematic review after evaluating 1210 non-duplicate records. There were nineteen of the twenty-one studies that were cohort studies and two studies had a nested case-control design. All of the included studies were of high quality according to the "Newcastle-Ottawa Scale". TMAO was positively associated with adverse cardiovascular events and CVD/all-cause mortality in some, but not all of the included studies. Bile acids were associated with atrial fibrillation and CVD/all-cause mortality, but not with CVD. Positive associations were found between BCAAs and CVD, and between indole derivatives and major adverse cardiovascular events, while a negative association was reported between tryptophan and all-cause mortality. No studies examining the relationship between SCFAs and CVD risk were identified. Evidence from prospective studies included in the systematic review supports a role of microbial metabolites in CVD.

SUBMITTER: Sanchez-Gimenez R

PROVIDER: S-EPMC9268449 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAccumulating evidence has suggested that human gut microbiota metabolize certain dietary compounds and subsequently produce bioactive metabolites that may exert beneficial or harmful effects on coronary artery disease (CAD) risk.ObjectivesThis study examined the joint association of 2 gut microbiota metabolites, enterolactone and trimethylamine N-oxide (TMAO), that originate from intake of plant-based foods and animal products, respectively, in relation to CAD risk.MethodsA prospective nested case-control study of CAD was conducted among participants who were free of diabetes, cardiovascular disease, and cancer in the Nurses' Health Study II and the Health Professionals Follow-up Study. Plasma concentrations of enterolactone and TMAO, as well as choline and L-carnitine, were assayed among 608 CAD case-control pairs.ResultsA high enterolactone and low TMAO profile was associated with better diet quality, especially higher intake of whole grains and fiber and lower intake of red meats, as well as lower concentrations of plasma triglycerides and C-reactive protein. Participants with a high enterolactone/low TMAO profile had a significantly lower risk of CAD: the multivariate-adjusted OR was 0.58 (95% CI: 0.38, 0.90), compared with participants with a low enterolactone/high TMAO profile. No significant interaction between enterolactone and TMAO on CAD risk was observed. Neither TMAO nor enterolactone alone were associated with CAD risk in pooled analyses. In women, a higher enterolactone concentration was significantly associated with a 54% lower CAD risk (P trend = 0.03), although the interaction by sex was not significant.ConclusionsOur results show that a profile characterized by high enterolactone and low TMAO concentrations in plasma is linked to a healthful dietary pattern and significantly associated with a lower risk of CAD. Overall, these data suggest that, compared with individual markers, multiple microbiota-derived metabolites may facilitate better differentiation of CAD risk and characterization of the relations between diet, microbiota, and CAD risk.

Project description:ObjectiveTo evaluate the association between egg intake and cardiovascular disease risk among women and men in the United States, and to conduct a meta-analysis of prospective cohort studies.DesignProspective cohort study, and a systematic review and meta-analysis of prospective cohort studies.SettingNurses' Health Study (NHS, 1980-2012), NHS II (1991-2013), Health Professionals' Follow-Up Study (HPFS, 1986-2012).ParticipantsCohort analyses included 83?349 women from NHS, 90?214 women from NHS II, and 42?055 men from HPFS who were free of cardiovascular disease, type 2 diabetes, and cancer at baseline.Main outcome measuresIncident cardiovascular disease, which included non-fatal myocardial infarction, fatal coronary heart disease, and stroke.ResultsOver up to 32 years of follow-up (>5.54 million person years), 14?806 participants with incident cardiovascular disease were identified in the three cohorts. Participants with a higher egg intake had a higher body mass index, were less likely to be treated with statins, and consumed more red meats. Most people consumed between one and less than five eggs per week. In the pooled multivariable analysis, consumption of at least one egg per day was not associated with incident cardiovascular disease risk after adjustment for updated lifestyle and dietary factors associated with egg intake (hazard ratio for at least one egg per day v less than one egg per month 0.93, 95% confidence interval 0.82 to 1.05). In the updated meta-analysis of prospective cohort studies (33 risk estimates, 1?720?108 participants, 139?195 cardiovascular disease events), an increase of one egg per day was not associated with cardiovascular disease risk (pooled relative risk 0.98, 95% confidence interval 0.93 to 1.03, I2=62.3%). Results were similar for coronary heart disease (21 risk estimates, 1?411?261 participants, 59?713 coronary heart disease events; 0.96, 0.91 to 1.03, I2=38.2%), and stroke (22 risk estimates, 1?059?315 participants, 53?617 stroke events; 0.99, 0.91 to 1.07, I2=71.5%). In analyses stratified by geographical location (P for interaction=0.07), no association was found between egg consumption and cardiovascular disease risk among US cohorts (1.01, 0.96 to 1.06, I2=30.8%) or European cohorts (1.05, 0.92 to 1.19, I2=64.7%), but an inverse association was seen in Asian cohorts (0.92, 0.85 to 0.99, I2=44.8%).ConclusionsResults from the three cohorts and from the updated meta-analysis show that moderate egg consumption (up to one egg per day) is not associated with cardiovascular disease risk overall, and is associated with potentially lower cardiovascular disease risk in Asian populations.Systematic review registrationPROSPERO CRD42019129650.

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Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies.

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