Abstract Body: Introduction: Xylitol, a sugar alcohol with a global market estimated at 161,500 metric tons, has been linked to increased thrombosis and risk of stroke and heart attack. Older adults with obesity and metabolic syndrome may have decreased elimination of the xylitol metabolite xylose, which may explain the higher observed risk of thrombosis and stroke in older adults who consume foods with sugar alcohols. MicroRNAs (miRs) have been associated with thrombosis and the blood clotting cascade and can provide additional insight about pathogenesis or biomarkers to help establish safe dietary intake guidelines. However, multiomics studies of both xylitol metabolites and these miRs in humans have not been done. This study aims to measure these associations in a sample of adults with obesity and metabolic syndrome.
Methods: We analyzed data from a subset of N=70 obese adults with metabolic syndrome who had both baseline metabolome and miR data from the PRYSMS randomized controlled trial. Pearson's correlations were used to test associations between xylitol, xylose, and 20 miRs associated with thrombosis and the clotting cascade, using the false discovery rate method to adjust for multiple comparisons.
Results: Participants were 55 ± 6 years (range 32-65) and 24% male. The mean BMI was 35.2 ± 7.4 kg/m2, HbA1c was 5.9% ± 0.4, fasting blood glucose was 103 ± 13 mg/dL, HDL cholesterol was 49 ± 10 mg/dL, and triglycerides were 173 ± 63 mg/dL. Xylose concentrations were inversely correlated with six miRs (miR-15b, miR-151a-3p, miR-151a-5p, miR-151b, miR-24-3p, and miR-27a-3p). Relevant target proteins of these miRs may include Factor XI (F11), Fibrinogen Alpha (F1 or FGG_A), Coagulation Factor VIII (F8), Von Wilebrand Factor (VWF), and Toxoplasma gondii (TFP1).
Conclusion: Our findings demonstrate an inverse association between xylose levels and six miRs associated with thrombosis and the clotting cascade in adults with obesity and metabolic syndrome. Xylitol metabolite concentration was not associated with any miRs in our sample, suggesting that circulating xylose may be a better indicator of clotting risk. Dietary intake of xylitol-containing foods may provide additional detail about these associations. Future research should explore multiomics relationships to refine and validate these results, to provide a more complex understanding of the biological processes involved for people at risk of T2D and stroke, and to help establish safe guidelines for dietary xylitol intake.