Cardiometabolic risk and gut microbial phytoestrogen metabolite phenotypes

Abstract

Recent evidence supports that the gut microbial community, independently and/or interactively with dietary intake, is a target for reducing cardiovascular disease risk through its effects on cardiometabolic risk factors. Dietary phytoestrogens may be a source for interactive effects. Phytoestrogens, such as isoflavones, lignans, and flavonoids, are compounds found in plants that have estrogenic or antiestrogenic activities, as well as antioxidant, antiproliferative, or apoptotic actions. Given these physiological activities, phytoestrogens may have a role in cardiometabolic health. Some phytoestrogens consumed in the diet undergo biotransformation through gut bacterial metabolism to other compounds that may exhibit similar or different physiological activity than the parent compound. There is interindividual variability in the capability to metabolize phytoestrogens to their metabolites, and there is a resulting phenotype that can be evaluated based on urinary metabolite excretion. Evidence suggests that phytoestrogen metabolites and/or phenotypes are associated with cardiometabolic risk factors, such as blood pressure, abdominal obesity, and serum lipids, triglycerides, glucose, and inflammatory markers. The objective of this review was to provide an overview of the observed associations between gut microbial phytoestrogen metabolites and metabolite phenotypes with cardiometabolic risk factors, with focus on the more extensively studied isoflavone metabolites.

The Human Metabolism of Nuts Proanthocyanidins does not Reveal Urinary Metabolites Consistent with Distinctive Gut Microbiota Metabotypes

“…Although the concept of metabotype is quite broad and different criteria have been described in the literature for its definition, the term ‘gut microbiota polyphenol metabotype’ refers to a metabolic phenotype characterized by specific polyphenol‐derived metabolites produced by a specific microbial ecology. Overall, this is not a quantitative but a qualitative criterion, (i.e., producer vs non‐producer), it is less influenced by external factors and mainly characterize individuals that harbor particular microbial ecologies . In this context, the stratification of individuals according to their gut microbiota polyphenol metabotypes has been proposed to understand individuals’ response to dietary polyphenols, which is crucial in the context of personalized nutrition …”

“…Remarkably, the distribution of urolithin metabotypes in the population has been reported to be mainly determined by aging . Regarding isoflavones, two metabotypes have been identified based on the excretion of the microbial metabolite equol, i.e., equol‐producers and non‐producers, although a third potential metabotype is currently being considered regarding those individuals that are not able to produce the metabolite O ‐desmethylangolensin (ODMA) . Therefore, i) polyphenol gut metabotypes are based on a binary response (presence vs absence of metabolites), ii) their possible confirmation requires the analysis of large cohorts, and iii) the inclusion of a number of potential variables such as age is mandatory in the multivariate analyses.…”

“…The stratification of individuals according to their ability to produce specific microbial metabolites has been clearly established for some polyphenols such as ellagitannins and isoflavones . Previous results suggest that the stratification of volunteers according to these metabotypes seems to be mandatory in the interpretation of ellagitannins and isoflavones effects . In this context, the characterization of human gut metabotypes related to the metabolism of other dietary polyphenols such as PAs is of great interest.…”

Evaluation of inter-individual differences in gut bacterial isoflavone bioactivation in humans by PCR-based targeting of genes involved in equol formation

“…; Birru et al . ; Frankenfeld ). The definition of the equol producer phenotype is currently based on urinary or serum equol concentrations.…”

“…By doing so, a number of human randomized controlled trials found beneficial effects of soy intake in equol-producing subjects but not in nonproducers. Those effects include improvement of risk factors for breast cancer, prostate cancer, cardiovascular disease and alleviation of osteoporosis (Shor et al 2012;Birru et al 2016;Frankenfeld 2017). The definition of the equol producer phenotype is currently based on urinary or serum equol concentrations.…”