Microbial Phenolic Metabolites in Urine Are Inversely Linked to Certain Features of Metabolic Syndrome in Spanish Adolescents

Abstract

(1) Background: To explore the association between microbial phenolic metabolites (MPM) and metabolic syndrome (MetS) and its clinical features in adolescents aged 12.02 ± 0.41 years. (2) Methods: a cross-sectional study was conducted in 560 participants at baseline in the SI! Program for Secondary Schools trial. The following MPM, coumaric acids (m-, o-, p-coumaric acids), dihydroxyphenylpropionic acid, dihydroresveratrol, enterolignans, gallic acid, hydroxybenzoic acids, hydroxyphenylacetic acid, hydroxytyrosol, protocatechuic acid, syringic acid, urolithins (A, B), and vanillic acid, were analyzed by HPLC-LTQ-Orbitrap-HRMS. MetS and its clinical features were defined in accordance with the International Diabetes Federation. (3) Results: Out of all MPM, urolithin A was inversely associated with the diastolic blood pressure z-score. Urolithin B was inversely associated with the MetS score and waist circumference z-score. Additionally, higher levels of gallic acid were associated with lower odds of presenting MetS (OR = 0.85, 95% CI: 0.77; 0.93) and abdominal obesity (OR = 0.93, 95% CI: 0.89; 0.98). Higher urolithin B levels were inversely associated with abdominal obesity (OR = 0.94, 95% CI: 0.89; 0.98) and high blood glucose (OR = 0.92, 95% CI:0.88; 0.96); (4) Conclusions: gallic acid, urolithin A and B were associated with lower odds of presenting MetS or some of its clinical features in adolescents. This is the first study that evaluates several MPM with MetS in adolescents, highlighting the importance of MPM on cardiometabolic health at early life stages.

Keywords: antioxidant compound; cardiovascular; microbiota; phytochemical.

Figure 1

Association between log-transformed groups of MPM and MetS score in adolescents. β coefficient, CI confidence interval, MetS metabolic syndrome, MPM microbial phenolic metabolites. Mixed-effects linear regression between log-transformed MPM and MetS score. Fixed effect: sex (female/male), age (continuous, years), Tanner maturation stage (score from I to V), physical activity (≥60 min/<60 min moderate-to-vigorous physical activity), household income (low/medium/high), and energy intake (continuous, kcal/day). Municipality and schools were considered as random effects). * p-adjusted for multiple-testing using the Benjamin–Hochberg procedure considering a false discovery rate < 0.05 as significant.

Figure 2

Association between log-transformed groups of MPM and cardiometabolic health parameters in adolescents. (A): WC z-score, (B): SBP- z-score, (C): DBP z-score, (D): TG, mg/dL, (E): HDL-c, mg/dL, (F): BG, mg/dL. β coefficient, BG blood glucose, CI confidence interval, DBP diastolic blood pressure, HDL-c high-density lipoprotein-cholesterol, MPM microbial phenolic metabolites, SBP systolic blood pressure, TG triglycerides, WC waist circumference. Mixed-effects linear regression between log-transformed MPM and cardiometabolic health parameters. Fixed effect: sex (female/male), age (continuous, year), Tanner maturation stage (score from I to V), physical activity (≥60 min/<60 min moderate-to-vigorous physical activity), household income (low/medium/high), and energy intake (continuous, kcal/day). Municipality and schools were considered random effects. * p-adjusted for multiple-testing using the Benjamin–Hochberg procedure, considering a false discovery rate < 0.05 as significant.

Figure 3

Log-transformed groups of MPM with MetS in adolescents. CI confidence interval, MetS metabolic syndrome; MPM microbial phenolic metabolites, OR odds ratio. Mixed effect logistic regression between groups of MPM (log-transformed, continuous) and MetS (dichotomous). Fixed effect: sex (female/male), age (continuous, years), Tanner maturation stage (score from I to V), physical activity (≥60 min/<60 min moderate-to-vigorous physical activity), household income (low/medium/high), and energy intake (continuous, kcal/day). Municipality and schools were considered as random effects. * p-adjusted for multiple-testing using the Benjamin–Hochberg procedure, considering a false discovery rate < 0.05 as significant.

Figure 4

Log-transformed groups of MPM with MetS clinical features in adolescents. (A): WC ≥ 90th, (B): TG ≥ 150 mg/dL, (C): HDL-c ≤ 40 mg/dL, (D): BG ≥ 110 mg/dL. BG blood glucose, CI confidence interval, HDL-c high-density lipoprotein-cholesterol, MPM microbial phenolic metabolites, TG triglycerides, WC waist circumference. Mixed-effects logistic regression between groups of MPM (log-transformed, continuous) and MetS clinical features (dichotomous). Fixed effect: sex (female/male), age (continuous, years), Tanner maturation stage (score from I to V), physical activity (≥60 min/<60 min moderate-to-vigorous physical activity), household income (low/medium/high), and energy intake (continuous, kcal/day). Municipality and schools were considered random effects. High blood pressure was not considered in the statistical analysis as only 2 participants had this condition (systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 85 mm Hg), and therefore analysis did not converge. * p-adjusted for multiple-testing using the Benjamin–Hochberg procedure, considering a false discovery rate < 0.05 as significant.