Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe–microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk.

Aim: To study the prevalence of hypertriglyceridemic waist (HTGW) in an urban adult Spanish population and its association with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Methods: We undertook a cross-sectional analysis in a random sample of 2270 individuals (18-80 years of age). All participants provided a clinical history and underwent a physical examination. Blood and urine analyses were conducted. HTGW was diagnosed using anthropometric criteria for the European population (waist circumference: for men, X94 cm; for women, X80 cm) and fasting plasma triglycerides (TGs) X1.71 mmol l À1 (X150 mg per 100 ml). Results: The prevalence of HTGW was 14.5% (men: 18.2%, women: 10.8%) and was significantly greater in men o59 years (Po0.001). HTGW was associated with older individuals, a low educational level and, in men, with a sedentary lifestyle (Po0.001). Subjects with HTGW had higher levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-c) and uric acid, lower levels of high-density lipoprotein-cholesterol, a higher blood pressure, a greater degree of obesity and a higher prevalence of T2DM (20.00 vs 6.4%, Po0.001) (odds ratio (OR) 3.61; 95% confidence interval (95% CI), 2.60-5.01) and CVD (8.5 vs 3.4%, Po0.001) (OR 2.63; 95% CI, 1.66-4.16). The association of HTGW with T2DM and CVD disappeared after adjusting for age. The degree of concordance between HTGW and the metabolic syndrome (MS) was moderate, with both the Adult Treatment Panel III Report (ATP-III) and the International Diabetes Federation criteria (k ¼ 0.51 and k ¼ 0.58, respectively). Subjects with isolated HTGW as compared with those with isolated MS (ATP-III) were younger, had greater levels of total cholesterol, LDL-c and TGs and a lower prevalence of obesity, high blood pressure and dysglycemia. Conclusion: HTGW is a phenotype of cardiometabolic risk prevalent in the adult population in our environment. HTGW may be an alternative to MS to detect the population at risk for T2DM and CVD, especially in young individuals who do not fulfill the criteria for MS.

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