Plasma metabolomic biomarkers of mixed nuts exposure inversely correlate with severity of metabolic syndrome

Scope: To identify the most discriminant dietary biomarkers of nuts exposure in subjects with metabolic syndrome (MetS), and investigate the potential association between exposure and the severity of the MetS diagnostic traits. Methods and results: We applied the untargeted LC-ESI-qToF-MS-driven metabolomic workflow to explore the changes occurring in the plasma metabolome of MetS subjects following 12-wk intake of mixed nuts (30 g/d; nuts versus control groups). Urolithin A glucuronide was the most discriminative biomarker of nuts exposure, showing the highest predictive capacity (area under the ROC curve = 89.6% [80.8-98.4]) despite the interindividual variation expected for a host-microbial cometabolite. Furthermore, the detection of urolithin A glucuronide in plasma showed significant inverse correlation with basal abdominal adiposity (waist circumference: r = -0.550, p < 0.01; waist-hip ratio: r = -0.409, p < 0.05) and impaired glycemic control (fasting insulin: r = -0.414, p < 0.05; HOMA-IR: r = -0.417, p < 0.05). Significant changes in medium-chain dicarboxylic acids, recognized as alternative energy substrates that are particularly relevant in the case of glycemic control impairment, were also associated with nut consumption. Conclusion: Higher levels of utolithin A glucuronide are reported in subjects with less severe MetS traits, especially in females. We believe that this inverse correlation may be related with profile of gut microbial dysbiosis, recently associated to subjects with MetS.