RESUMEN
An untargeted NMR-based metabonomics approach was used to evaluate the effects of pure resveratrol (RSV, 50 and 250 mg/kg per os) on the urinary and faecal metabolome of normal female Wistar rats. Multivariate data analysis on both the endogenous and xenobiotic metabotype of RSV provided an insight into its metabolic fate and influence on endogenous metabolites. The xenobiotic trajectory shows that RSV is highly metabolized within the first 12 h, the period of the most significant variation of endogenous metabolites. The results reveal alterations in gut microbiota co-metabolites, mainly at the high dose of RSV, such as hippurate, phenylacetyl glycine (PAG), p-cresyl glucuronide (p-CG), p-cresyl sulfate (p-CS) and 3-indoxylsulfate (3IS), as well as in osmolytes (creatine, creatinine, taurine and proline betaine). This metabolic variation could mean that RSV modulates the composition and/or function of the gut microbiota as well as its interaction with the host through the gut-microbiome-liver-kidney axis. For instance, RSV may interact with conjugating enzymes present in the intestine and liver. There were also modifications in metabolites of the tricarboxylic acid (TCA) cycle and energy metabolism (2-oxoglutarate, lactate and alanine), and diet-derived metabolites (pantothenate and trans-aconitate). These effects of RSV are perhaps related to its capacity to control energy homeostasis, provide renal protection, and downregulate some biomarkers of oxidative stress (e.g., glycoproteins). Such changes contribute to reduced oxidative stress and inflammation, which are associated with RSV-induced biological activity to improve various conditions, including metabolic disorders, obesity, and chronic and cardiovascular diseases.