Application of MS-Based Metabolomics to Investigate Biomarkers of Apple Consumption Resulting from Microbiota and Host Metabolism Interactions

Two nutritional clinical trials were designed to study apple metabolism in humans, giving access to acute postprandial kinetics (AGER) and to biomarkers of long-term intake. Changes in the composition of plasma and urine were analyzed via untargeted metabolomics. From the combination of these studies, we identified 88 specific blood and urine metabolic biomarkers of apple polyphenol intake and found evidence of phloretin glucuronide and phloretin glucuronide sulfate as promising biomarkers of apple intake, considering the evaluation of several criteria such as specificity, plausibility, time–response and dose–response. Moreover, we suggest that properly designed metabolomic experiments can be used within a multiomic dataset, supporting bottom-up exploration of the correlations between metabolites modulated significantly by dietary intervention and fecal microbiota species at the genus level. This approach supports the discovery of putative associations of polyphenol metabolites with specific genera of fecal bacteria, associations which then need confirmation and validation in specifically designed mechanistic studies.