Introduction Phenolic acids are important phenolic compounds widespread in foods, contributing to nutritional and organoleptic properties. Factors affceting individual variability The bioavailability of these compounds depends on their free or conjugated presence in food matrices, which is also affected by food processing. Phenolic acids undergo metabolism by the host and residing intestinal microbiota, which causes conjugations and structural modifications of the compounds. Human responses, metabolite profiles and health responses of phenolics, show considerable individual variation, which is affected by absorption, metabolism and genetic variations of subjects. Opinion A better understanding of the gut-host interplay and microbiome biochemistry is becoming highly relevant in understanding the impact of diet and its constituents. It is common to study metabolism and health benefits separately, with some exceptions; however, it should be preferred that health responders and non-responders are studied in combination with explanatory metabolite profiles and gene variants. This approach could turn interindividual variation from a problem in human research to an asset for research on personalized nutrition.

Background: The mechanism behind the lowered postprandial insulin demand observed after rye bread intake compared to wheat bread is unknown. The aim of this study was to use the metabolomics approach to identify potential metabolites related to amino acid metabolism involved in this mechanism. Methods: A sourdough fermented endosperm rye bread (RB) and a standard white wheat bread (WB) as a reference were served in random order to 16 healthy subjects. Test bread portions contained 50 g available carbohydrate. In vitro hydrolysis of starch and protein were performed for both test breads. Blood samples for measuring glucose and insulin concentrations were drawn over 4 h and gastric emptying rate (GER) was measured. Changes in the plasma metabolome were investigated by applying a comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry metabolomics platform (GC×GC-TOF-MS). Results: Plasma insulin response to RB was lower than to WB at 30 min (P = 0.004), 45 min (P = 0.002) and 60 min (P < 0.001) after bread intake, and plasma glucose response was significantly higher at time point 90 min after RB than WB intake (P = 0.045). The starch hydrolysis rate was higher for RB than WB, contrary to the in vitro protein digestibility. There were no differences in GER between breads. From 255 metabolites identified by the metabolomics platform, 26 showed significant postprandial relative changes after 30 minutes of bread intake (p and q values < 0.05). Among them, there were changes in essential amino acids (phenylalanine, methionine, tyrosine and glutamic acid), metabolites involved in the tricarboxylic acid cycle (alpha-ketoglutaric, pyruvic acid and citric acid) and several organic acids. Interestingly, the levels of two compounds involved in the tryptophan metabolism (picolinic acid, ribitol) significantly changed depending on the different bread intake. Conclusions: A single meal of a low fibre sourdough rye bread producing low postprandial insulin response brings in several changes in plasma amino acids and their metabolites and some of these might have properties beneficial for health.