Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes

Abstract The full consensus on the role of dietary polyphenols as human‐health‐promoting compounds remains elusive. The two‐way interaction between polyphenols and gut microbiota (GM) (i.e., modulation of GM by polyphenols and their catabolism by the GM) is determinant in polyphenols’ effects. The identification of human metabotypes associated with a differential gut microbial metabolism of polyphenols has opened new research scenarios to explain the inter‐individual variability upon polyphenols consumption. The metabotypes unequivocally identified so far are those involved in the metabolism of isoflavones (equol and(or) O ‐desmethylangolesin producers versus non‐producers) and ellagic acid (urolithin metabotypes, including producers of only urolithin‐A (UM‐A), producers of urolithin‐A, isourolithin‐A, and urolithin‐B (UM‐B), and non‐producers (UM‐0)). In addition, the microbial metabolites (phenolic‐derived postbiotics) such as equol, urolithins, valerolactones, enterolactone, and enterodiol, and 8‐prenylnaringenin, among others, can exert differential health effects. The knowledge is updated and position is taken here on i) the two‐way interaction between GM and polyphenols, ii) the evidence between phenolic‐derived postbiotics and health, iii) the role of metabotypes as biomarkers of GM and the clustering of individuals depending on their metabotypes (metabotyping) to explain polyphenols’ effects, and iv) the gut microbial metabolism of catecholamines to illustrate the intersection between personalized nutrition and precision medicine.