Phytoestrogen Metabolism by Adult Human Gut Microbiota

Abstract

Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed.

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

“…Dihydrodaidzein was formed as an intermediate or a final metabolite by all but one of the tested microbiomes. This is in agreement with previous studies demonstrating the conversion of daidzein to dihydrodaidzein or genistein to dihydrogenistein in 70-90% of the human FS tested (Gardana et al 2009;Braune et al 2010;Gaya et al 2016).…”

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

“…2 and 5) [64]. The unique catabolites include 4-hydroxy-mandelic acid from p-sympatol [65], tyrosols from oleuropein and related compounds [66], S-equol, 5-hydroxy-equol and dihydrocinnamic acids with the aryl residue at C2 formed from isoflavones [67,68], urolithins and nasutins from ellagitannins [69][70][71], diarylbutanes from lignans [32;35;36], and dihydroresveratrol from piceid and resveratrol [72]. The avenanthramides of oats, N-cinnamoyl conjugates of anthranilic acids, yield some unique catabolites, e.g.…”

Use of Phytoestrogens for the Treatment of Psychiatric Symptoms Associated with Menopause Transition

“…Rodents fed with soy also showed less body weight [64]. Unfortunately, in this paper, the authors did not indicate the phytoestrogens bounded with the behavioral efect but reported high levels of equol in plasma, the more active metabolite of isolavones found in the soy [14].…”

“…The extract from roots of rhubard mainly consists of rhaponticin and desoxyrhaponticin, which are converted to the resveratrol-like aglycones rhapontigenin and desoxyrhapontigenin by the microbiome. Rhapontigenin is more active than desoxyrhapontigenin, and it is suggested that P 450 -catalyzed O-demethylation giving the resveratrol-catechol piceatannol might be responsible for its estrogenic activity [14,55]. Clinical trials show that the rhubarb extract was efective and successfully decreased the Menopause Rating Scale and increased QoL [56][57][58].…”

“…There are a wide variety of polyphenols but, in general, they have been classiied into two groups according to their chemicals properties: lavonoids and non-lavonoids (Figure 1). The types of phytoestrogens are isolavones, lignans, coumestans, ellagitannins and stilbens [13][14][15]. Figure 3 shows the main sources of phytoestrogens and the phytochemicals with estrogenic properties.…”