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-healthpromoting 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.A. Cortés-Martín, Dr.

Postbiotics—A Step Beyond Pre- and Probiotics

“…Polyphenols modulate the structure and are concurrently metabolized by gut microbiota. Hosts' responses to the dietary interventions may differ and this observation formed the basis for developing term called "metabotype" [71]. Metabotyping investigates the relationship between a metabolic phenotype and gut microbiome-derived metabolites that characterize the metabolism of the parent compound, thus providing a rationale for developing "personalized nutrition" [72].…”

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives

“…The low number of volunteers, as well as the specific selection criteria of the volunteers selected in the different studies, are key factors to understand the high variability reported. Genetic polymorphisms or differences in the composition or functionality of the gut microbiota will also contribute to the different response of individuals to interventions with polyphenol-rich foods [48,[144][145][146]. In this regard, a highly variable metabolism between individuals has been described for some phenolic compounds.…”

“…This allows for grouping the population according to the excretion of the metabolized compound into "high or low producers", as it occurs in the metabolism of the phenolic precursor-derived metabolite pairs hesperidin-hesperetin [147], lignans-enterolignans [148], ellagic acid-urolithins [149] and procyanidins-valerolactones [150,151]. Besides, specific metabotypes, attributed to the different composition and functionality of the gut microbiota, have been described in the case of urolithins [146,152] or isoflavones [153], allowing the stratification of individuals based on the production of specific metabolites associated with a particular gut microbiota ecology. Thus, the inter-individual variability related to bioavailability and metabolism of dietary phenolics is essential to comprehend the results in clinical studies and to identify whether the possible beneficial effects can be extrapolated to the whole population or only to certain specific individuals [146].…”

“…Besides, specific metabotypes, attributed to the different composition and functionality of the gut microbiota, have been described in the case of urolithins [146,152] or isoflavones [153], allowing the stratification of individuals based on the production of specific metabolites associated with a particular gut microbiota ecology. Thus, the inter-individual variability related to bioavailability and metabolism of dietary phenolics is essential to comprehend the results in clinical studies and to identify whether the possible beneficial effects can be extrapolated to the whole population or only to certain specific individuals [146]. Future research should be conducted to evaluate associations between specific phenolic-related gut microbiota metabotypes and protective effects against BC.…”

Modifications of Gut Microbiota after Grape Pomace Supplementation in Subjects at Cardiometabolic Risk: A Randomized Cross-Over Controlled Clinical Trial

“…Not all subjects exhibit the same response to supplementation (e.g., with polyphenols) [22]. The action of microbiota is probably a major determinant of inter-individual variability as polyphenols are extensively transformed by several bacterial species, which generate a great variety of bioactive absorbable metabolites [23]. Indeed, the concept of metabotypes, i.e., groups of subjects with a tendency to originate certain combinations of circulating polyphenol metabolites as compared to other groups not able to generate them, has become a key concept in the field of dietary polyphenols [24].…”