Equol Concentrations Research Articles

Production of equol, dehydroequol, 5-hydroxy-equol and 5-hydroxy-dehydroequol in soy beverages by the action of dihydrodaidzein reductase in Limosilactobacillus fermentum strains

Equol and 5-hydroxy-equol, and their analogous compounds dehydroequol and 5-hydroxy-dehydroequol, are bioactive isoflavones formed by microbial metabolism. The aims of this work were to elucidate the formation of dehydroequol and 5-hydroxy-dehydroequol, to identify the role of dihydrodaidzein reductase (DHDR) in the production of equol, dehydroequol, 5-hydroxy-equol and 5-hydroxy-dehydroequol and to develop soy beverages enriched in these compounds through engineered lactic acid bacteria. DHDR was responsible for the production of equol and dehydroequol from dihydrodaidzein (DHD), and of 5-hydroxy-equol and 5-hydroxy-dehydroequol from dihydrogenistein (DHG), even in the absence of tetrahydrodaidzein reductase (THDR). The combination of DHDR with dihydrodaidzein racemase (DDRC), and/or THDR, allowed the production of soy beverages enriched in equol (241.34 ± 34.56 μM), dehydroequol (31.23 ± 5.78 μM), 5-hydroxy-equol (125.54 ± 7.90 μM) and 5-hydroxy-dehydroequol (292.34 ± 14.67 μM). Beverages fortified with high concentrations of equol, 5-hydroxy-dehydroequol and 5-hydroxy-equol could provide significant health benefits for consumers.

Bacteroides salyersiae Is a Candidate Probiotic Species with Potential Anti-Colitis Properties in the Human Colon: First Evidence from an In Vivo Mouse Model.

Previous studies have indicated a critical role of intestinal bacteria in the pathogenesis of ulcerative colitis (UC). B. salyersiae is a commensal species from the human gut microbiota. However, what effect it has on UC development has not been investigated. In the present study, we explored this issue and demonstrated for the first time that oral administration of B. salyersiae CSP6, a bacterium previously isolated from the fecal sample of a healthy individual, protected against dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. In particular, B. salyersiae CSP6 improved mucosal damage and attenuated gut dysbiosis in the colon of DSS-fed mice. Specifically, B. salyersiae CSP6 decreased the population of pathogenic Escherichia-Shigella spp. and increased the abundance of probiotic Dubosiella spp. and Bifidobacterium pseudolongum. Additionally, by reshaping the colonic microbiota, B. salyersiae CSP6 remarkably increased the fecal concentrations of equol, 8-deoxylactucin, and tiglic acid, three beneficial metabolites that have been well documented to exert strong anti-inflammatory effects. Altogether, our study provides novel evidence that B. salyersiae is a candidate probiotic species with potential anti-colitis properties in the human colon, which has applications for the development of next-generation probiotics.

Urinary Equol and Equol-Predicting Microbial Genera Are Favorably Associated with Body Fat Measures among Chinese Adults

BackgroundMany studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. ObjectivesWe aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. MethodsIn this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. ResultsAmong 305 participants (median age: 50 y, IQR, 37–59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (β = −0.013, P < 0.001) and body fat mass (β= −0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (β = −0.040, P = 0.011). ConclusionsHigh urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.

Urinary Equol and Equol-Predicting Microbial Species Are Favorably Associated With Cardiometabolic Risk Markers in Chinese Adults.

The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones including daidzein, glycitein, genistein, equol (a gut microbial metabolite of daidzein), and equol-predicting microbial species with cardiometabolic risk markers. In a 1-year study of 305 Chinese community-dwelling adults aged ≥18 years, urinary isoflavones, fecal microbiota, blood pressure, blood glucose and lipids, and anthropometric data were measured twice, 1 year apart. Brachial-ankle pulse wave velocity was also measured after 1 year. A linear mixed-effects model was used to analyze repeated measurements. Logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% CI for the associations for arterial stiffness. Each 1 μg/g creatinine increase in urinary equol concentrations was associated with 1.47%, 0.96%, and 3.32% decrease in triglycerides, plasma atherogenic index, and metabolic syndrome score, respectively (all P<0.05), and 0.61% increase in high-density lipoprotein cholesterol (P=0.025). Urinary equol was also associated with lower risk of arterial stiffness (aOR, 0.28 [95% CI, 0.09-0.90]; Ptrend=0.036). We identified 21 bacterial genera whose relative abundance was positively associated with urinary equol (false discovery rate-corrected P<0.05) and constructed a microbial species score to reflect the overall equol-predicting capacity. This score (per 1-point increase) was inversely associated with triglycerides (percentage difference=-1.48%), plasma atherogenic index (percentage difference=-0.85%), and the risk of arterial stiffness (aOR, 0.27 [95% CI, 0.08-0.88]; all P<0.05). Our findings suggest that urinary equol and equol-predicting microbial species may improve cardiometabolic risk parameters in Chinese adults.

The relationship between equol production status and normal tension glaucoma

PurposeEquol is metabolized by intestinal bacteria from soy isoflavones and is chemically similar to estrogen. Dietary habits, such as consumption of soy products, influence equol production. A relationship between glaucoma and estrogen has been identified; here, we investigated the relationship between equol production status and glaucoma in Japan.MethodsWe recruited 68 normal-tension glaucoma (NTG) patients (male to female ratio 26:42, average age 63.0 ± 7.6 years) and 31 controls (male to female ratio 13:18, average age 66.0 ± 6.3 years) from our hospital. All women included were postmenopausal. Urinary equol concentration was quantified with the ELISA method. MD was calculated based on the Humphrey visual field. The association between MD and equol was analyzed with Spearman’s rank correlation coefficient. The Mann–Whitney U test was used to compare the equol-producing (> 1 μM) and non-producing (< 1 μM) subjects. We also investigated the association between equol and glaucoma with a logistic regression analysis.ResultsThere was a significant association between equol and MD (r = 0.36, P < 0.01) in the NTG patients. Glaucoma, represented by MD, was significantly milder in the equol-producing subjects than the non-equol producing subjects (P = 0.03). A multivariate analysis revealed the independent contributions of equol, cpRNFLT, and IOP to MD (P = 0.03, P = 0.04, and P < 0.01, respectively).ConclusionOur results suggest that equol, acting through estrogen receptor-mediated neuroprotective effects, might be involved in suppressing the progression of NTG. This result also adds to evidence that glaucoma may be influenced by lifestyle.

Comparison of blood and urine concentrations of equol by LC‒MS/MS method and factors associated with equol production in 466 Japanese men and women.

Equol is produced from daidzein by the action of gut bacteria on soy isoflavones. However, not all people can produce equol, and metabolism differs even among the producers. We aimed to examine the equol producer status in both men and women, and investigate the relationships among the serum and urinary isoflavones as well as to other biomedical parameters. In this study, we measured the equol and daidzein concentrations from the blood and urine of 292 men and 174 women aged between 22 and 88 years by liquid chromatography-tandem mass spectrometry (LC‒MS/MS). We then analysed the cut-off value for equol producers in both sexes, the relationship of serum and urinary equol concentrations, and other parameters, such as sex, age, endocrine function, glucose metabolism, lipid metabolism, and renal function with regards to equol-producing ability, among the different age groups. Equol producers were defined as those whose log ratio of urinary equol and daidzein concentration or log (equol/daidzein) was -1.42 or higher. Among 466 participants, 195 were equol producers (42%). The proportion of equol producers was larger in women. The cut-off value for equol producers was consistent in both sexes. Positive relationships were noted between serum and urinary equol levels in equol producers of both sexes; however, such a relationship was not detected in nonproducers. Lipid and uric acid abnormalities were more common with non equol producers in both men and women. Prostate specific antigen (PSA) levels in men were significantly lower in equol producers, especially in those in their 40 s. This study suggests a relationship between equol-producing ability and reduced risk of prostate disease as well as positive effects of equol on blood lipids and uric acid levels. However, lack of dietary information and disperse age groups were major drawbacks in generalizing the results of this study.

Comparison of the five different definitions of equol producers: The relationship between blood and urine equol concentrations and blood parameters in 466 healthy men and women

Background and aimsNo studies have compared various definitions of “equol producers” until now. Therefore, we aimed to explore the accuracy of five different definitions of equol producers (EQP) and their associations with health benefits. MethodsThis is a cross-sectional study of 466 healthy Japanese men and women aged between 22 and 88 years. Equol producer proportions were calculated from their serum and urine isoflavone concentrations using five commonly used definitions. We then examined their accuracy, and associations with the blood parameters. ResultsProportions of equol ranged from 29 % in the most stringent definition to 47.6 % in the most sensitive definition. EQP identified under all definitions had significantly low serum PSA11PSA: prostate specific antigen. levels compared to nonequol producers (NEQP). The most stringent definition, which is defined as the urinary equol level of 1.0 μM and above, corresponded to the highest median serum equol level and was associated with better health outcomes. Male EQP identified by this definition seemed to have reduced risk of LDL22LDL: low density lipoprotein-hypercholesterolemia by 50 %, and female EQP identified by this definition seemed to have lower risk of high hs-CRP,33CRP: C-reactive protein compared to NEQP. Both the first and second stringent definition, which is defined as the serum equol level of 1.0 ng/mL and above, was associated with lower thyroid stimulating hormone level. ConclusionsMore stringent definitions were associated with better parameters in general. Combined with the dietary inquires, a reliable definition for equol producer is crucial to evaluate the health benefits of equol.

Exploring functional genes' correlation with (S)-equol concentration and new daidzein racemase identification.

(S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.

Abstract WP263: Associations of Equol-Producing Status With Cardioembolic Stroke in Japanese Patients With Stroke

Introduction: Equol, a metabolite of a soy isoflavone daidzein transformed by the gut microbiota, is associated with the amelioration of cardiovascular diseases and cognitive impairment. Approximately 50% of Asians and 30% of Westerners may be equol producers depending on the presence of equol-producing gut microbiota. It is still unknown whether equol-producing status is associated with development of stroke and its prognosis. Methods: In this single-center, retrospective study, we investigated the serum concentration of equol in 200 patients with stroke hospitalized in the National Cerebral and Cardiovascular Center (NCVC) from September 2019 to October 2021, and 103 healthy subjects registered in the Suita Study, a population-based cohort study at NCVC from November 2016 to September 2018. The concentration of equol was measured using liquid chromatography-mass spectrometry. Results: Eighty-five patients with stroke (43.5%) and 50 healthy subjects (48.5%) were equol producers ( p =0.32). However, patients with cardioembolic stroke (CES) had a significantly lower frequency of the equol producers (28.9%) compared to healthy subjects ( p =0.04), as well as patients with other stroke subtypes (48.0%) ( p =0.04). The prevalence of atrial fibrillation was significantly lower in equol producers than that in non-producers (26.3% vs. 47.3%, p =0.04) among patients with ischemic stroke. Additionally, equol-producing status was an independent predictor for a favorable outcome (modified Rankin scale 0-2) at discharge for ischemic stroke in a multivariable logistic regression analysis (odds ratio 2.75, 95% confidential interval 1.05-7.27, p =0.04). Discussion: CES, atrial fibrillation, and clinical outcome may be influenced by equol-producing status. These findings could provide new insights into the racial difference in the prevalence of CES between Asians and Westerners.

Association between lignan polyphenol bioavailability and enterotypes of isoflavone metabolism: A cross-sectional analysis.

Lignan polyphenols derived from plants are metabolized by bacteria in the gut to mammalian lignans, such as enterolactone (ENL) and enterodiol (END). Mammalian lignan intake has been reported to be associated with obesity and low blood glucose levels. However, the factors that are responsible for individual differences in the metabolic capacity for ENL and END are not well understood. In the present study, the effects of enterotypes of isoflavone metabolism, equol producers (EQP) and O-desmethylangolensin producers (O-DMAP), on lignan metabolism were examined. EQP was defined by urinary daidzein (DAI) and equol concentrations as log(equol/DAI) ≥ -1.42. O-DMAP was defined by urinary DAI and O-DMA concentrations as O-DMA/DAI > 0.018. Isoflavone and lignan concentrations in urine samples from 440 Japanese women were measured by gas chromatography-mass spectrometry. Metabolic enterotypes were determined from the urinary equol and O-DMA concentrations. Urinary END and ENL concentrations were compared in four groups, combinations of EQP (+/-) and O-DMAP (+/-). The urinary lignan concentration was significantly higher in the O-DMAP/EQP group (ENL: P<0.001, END: P<0.001), and this association remained significant after adjusting for several background variables (END: β = 0.138, P = 0.00607 for EQP and β = 0.147, P = 0.00328 for O-DMAP; ENL: β = 0.312, P<0.001 for EQP and β = 0.210, P<0.001 for O-DMAP). The ENL/END ratio was also highest in the O-DMAP/EQP group, indicating that equol and O-DMA metabolizing gut bacteria may be involved in lignan metabolism. In conclusion, urinary lignan concentrations were significantly higher in groups containing either EQP or O-DMAP than in the non-EQP/non-O-DMAP group. The variables and participants in this study were limited, which the possibility of confounding by other variables cannot be ruled out. However, there are no established determinants of lignan metabolism to date. Further research is needed to determine what factors should be considered, and to examine in different settings to confirm the external validity.

EQUOL, A SOYBEAN METABOLITE WITH ESTROGEN-LIKE FUNCTIONS, DECREASES LIPOPOLYSACCHARIDE-INDUCED HUMAN NEUTROPHIL EXTRACELLULAR TRAPS IN VITRO.

Objective: Neutrophil extracellular traps (NETs) defend against acute infections. However, their overexpression causes organ failure during sepsis. Control of NET formation may improve the outcomes of patients with sepsis. Equol, a soybean isoflavone, is a female hormone analog, which prevents inflammation. We evaluated the effects of equol on NET formation in human neutrophils during inflammatory stimulation in vitro . Methods: Healthy volunteers provided blood samples. An enzyme-linked immunosorbent assay assessed serum equol concentrations. Neutrophil extracellular trap formation in neutrophils was induced by lipopolysaccharide treatment. Enzyme-linked immunosorbent assay quantified DNA-binding elastase, and immunostaining assessed NET formation. Reverse-transcription quantitative polymerase chain reaction and Western blotting detected G-protein-coupled receptor 30 (GPR30) or peptidyl arginine deiminase 4 (PAD4) expression. Flow cytometry assessed neutrophil phagocytic ability with inactivated Escherichia coli . Results: In neutrophils derived from males with low-serum equol levels (low-serum equol group), equol significantly decreased DNA-binding elastase levels and NET formation. Equol did not decrease NETs in neutrophils from males with high-serum equol levels. GPR30 expression of neutrophils was higher in the low-serum than in the high-serum equol group. PAD4 mRNA levels and nuclear PAD4 protein expression also decreased more than the vehicle control in the low-serum equol group. Equol did not alter the phagocytic ability of neutrophils. In neutrophils from young females, equol had no inhibitory effect on NET formation. Conclusions: Equol decreases lipopolysaccharide-induced NET formation in neutrophils from males via inhibition of PAD4 expression. Our findings provide a rationale for investigating a new therapeutic approach using equol to control neutrophil activity during sepsis.

Association between equol and non-alcoholic fatty liver disease in Japanese women in their 50s and 60s.

Equol is a metabolite of soy isoflavone and has estrogenic activity. The incidence of non-alcoholic fatty liver disease (NAFLD) increases after menopause in women, which is thought to result in a decrease in estrogen. This study aimed to evaluate the association between equol and NAFLD. We evaluated 1185 women aged 50-69years who underwent health check-ups at four health centers in Fukushima, Japan. Equol producers were defined by a urinary equol concentration of 1.0μM or more. In addition to comparison between equol producers and non-producers, the association between equol and NAFLD was estimated using logistic regression analysis adjusting for fast walking and eating habits. Of the 1185 participants, 345 (29.1%) women were equol producers. The proportions of women who had NAFLD (34.8% vs 45.2%) were significantly lower in the equol-producing group than in the non-producing group. Multivariable logistic regression analysis showed that equol production was significantly associated with NAFLD (odds ratio=0.66, 95% confidence interval: 0.51-0.86). Equol production was significantly associated with NAFLD in women in their 50s and 60s.

Association between equol producers and type 2 diabetes mellitus among Japanese older adults.

Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non-producers and type 2 diabetes. The participants included 147 patients with typediabetes mellitus aged 70-89 years, and 147 age- and sex-matched controls. To ascertain the equol producers or non-producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut-off value -1.75). The urinary equol concentration was significantly lower in the diabetes group compared with the non-diabetes group (P=0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non-diabetes group; P=0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non-diabetes group (52.8%; P < 0.01). Additionally, the frequency of dyslipidemia in female equol producers was significantly lower than that in female non-equol producers (P < 0.01). Among men, no such differences were observed. We found a significant positive correlation between the urinary equol and daidzein concentrations among equol producers (r=0.55, P < 0.01). Our study findings showed that postmenopausal women had a low proportion of equol producers with diabetes and dyslipidemia.

Feeding Soy Protein Concentrates with Low and High Isoflavones Alters 9 and 18 Weeks Serum Isoflavones and Inflammatory Protein Levels in Lean and Obese Zucker Rats

Soy's anti-inflammatory properties contribute to the health benefits of soy foods. This study was designed to investigate the bioavailability of soy isoflavones and whether the isoflavone content of soy protein concentrate diet would affect serum inflammatory proteins in an obese (fa/fa) Zucker rat model. Six-week-old male lean (L) and obese (O) Zucker rats were fed a casein control diet (C), soy protein concentrate with low isoflavones (SPC-LIF), or soy protein concentrate with high isoflavones (SPC-HIF) (7 rats/dietary group) before being killed at 9 and 18 weeks. Serum samples were analyzed for isoflavones and inflammatory proteins. At both time points, serum total (aglycone + conjugates) genistein, daidzein, and equol concentrations were significantly higher in L-SPC-HIF and O-SPC-HIF groups compared with L-SPC-LIF and O-SPC-LIF groups, respectively, and were not detectable in either L-C or O-C groups. At week 9, serum C-reactive protein (CRP) concentration was significantly lower in O-SPC-HIF group compared with O-C and O-SPC-LIF group, whereas proteins tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels did not differ between any groups. At week 18, serum CRP levels in both O-SPC-HIF and O-SPC-LIF groups were significantly lower compared with the O-C group. TNF-α level was higher in the O-SPC-LIF group compared with both O-C and O-SPC-HIF groups, whereas IL-6 levels were not different between any groups. Taken together, feeding Zucker rats SPC-LIF and SPC-HIF diets led to different serum isoflavone concentrations in both L and O Zucker rats and altered CRP and TNF-α levels in obese Zucker rats compared with controls.

Association between urinary zinc excretion and isoflavone-metabolizing enterotypes among Japanese females: a cross-sectional study.

Zinc absorption and competition among gut bacteria have been reported in animal studies. Thus, gut bacteria may modify zinc availability in humans. Metabolism of intestinal bacteria is known to be necessary for the activation of several phytoconstituents in the body. For example, equol, a typical substance of soybean isoflavone, is produced by intestinal bacteria metabolizing daidzein and the enterotype is one of distinct ones among Japanese population. The difference in the intestinal microflora can modify the bioavailability of zinc. In this study, we examined urinary zinc concentrations in adult female equol producers (EQPs). Urine samples from women participating in health examinations in Miyagi, Okinawa, Kyoto, Kochi, and Hokkaido prefectures were used; from total 17,484 samples, approximately 25 samples were randomly selected for each age group from 30 to 60 years per region (subsample: n = 520), and 520 samples with available urinary zinc concentration (determined by flame atomic absorption analysis) and enterobacterial type were analyzed. EQP was defined as log(equol/daidzein) ≥ -1.42, and urinary concentrations were corrected for creatinine concentration. Urinary zinc concentrations were compared by Student's t-test and multiple regression analyses. The geometric mean urinary zinc concentration (µg/g-Cr) was lower in EQP than in non-EQP (p = 0.0136 by t-test after logarithm transformation). On the other hand, there was no correlation between urinary zinc concentration with daidzein (r = -0.0495, P = 0.436) and equol concentrations (r = -0.0721, P = 0.256). There was a significant negative association between urinary zinc concentration and EQP (β = -0.392, P = 0.0311) after adjusting with other potential confounding variables, such as daidzein intake. The results suggest that gut bacteria that produce equol are involved in the metabolism of zinc. Based on previous studies, the bacteria that affect the metabolism of both substances are thought to be Enterococcus. Future studies are expected to identify specific intestinal bacteria for zinc availability and understand individual differences in the effects of micronutrients.

Association of urinary phytoestrogens with hormone-related cancers and cancer biomarkers: NHANES 1999-2010.

Phytoestrogens may have potential effects on hormone-related cancers (HRC) and cancer biomarkers, but the findings have been inconsistent so far. Participants from the National Health and Nutrition Examination Survey 1999-2010 with information on the levels of urinary phytoestrogens, serum cancer biomarkers and cancer history were included. Sampling-weighted logistic regression models examined the association between urinary phytoestrogens concentrations (creatinine-standardised and log-transformed) and HRC, followed by stratified analyses by race/ethnicity, age and menopausal status for different gender. Correlation analyses between phytoestrogens and cancer biomarkers were performed. Of the total 8844 participants, there were 373 with HRC. We observed total isoflavone and enterodiol excretion were positively associated with HRC, especially in non-Hispanic white female subpopulations (Ptrend < 0·05). Similar association also existed in the total isoflavones and enterodiol levels with breast cancer. Whereas the highest concentration of total isoflavones was significantly linked to a reduced prevalence of HRC (OR = 0·40, 95 % CI: 0·19, 0·84) in white males and of prostate cancer (OR = 0·40, 95 % CI: 0·18, 0·86). Among twenty-four participants with HRC, urinary equol concentration was positively correlated with CA15.3. Also, an inverse correlation of total prostate-specific antigens (PSA) and positive correlation of the PSA ratio with urinary enterolactone were detected in thirteen prostate cancer patients. Our findings indicated that higher concentrations of total isoflavones and enterodiol were positively associated with HRC. Urinary certain phytoestrogen excretion may affect serum cancer biomarker levels in cancer patients. But further prospective studies are needed to provide stronger evidence.

Age-Related Changes, Influencing Factors, and Crosstalk Between Vaginal and Gut Microbiota: A Cross-Sectional Comparative Study of Pre- and Postmenopausal Women.

Objective: The ideal vaginal environment is maintained by Lactobacillus species, which keep the vagina clean and free of infections, boost fertility and immunity. Age-related decline in estrogen affects Lactobacillus population, leading to dominance of nonoptimal species and increased diversity in vaginal microbiota. In this study, we compared the differences between the vaginal microbiota of pre- and postmenopausal women. We also examined the relationships between vaginal and gut microbiota, their relationships with sex hormones and equol-producing ability. Materials and Methods: This was a cross-sectional study of 35 premenopausal and 35 postmenopausal women (age range: 27-76 years). We compared parameters such as the composition of the gut and vaginal microbiota, vaginal pH, estradiol, follicular stimulating hormone, and urinary equol concentration. Results: In the vaginal microbiota of premenopausal women, Lactobacillus species constituted ∼71.98%, and nonoptimal species constituted ∼16.87%. They were 10.08% and 26.78%, respectively, in the vaginal microbiota of postmenopausal women. The proportion of Lactobacillus was significantly low, whereas microbial diversity and vaginal pH were significantly high (p < 0.0001) in postmenopausal women. The compositions of the vaginal microbiota were significantly different in pre- and postmenopausal women. However, such differences were not noticeable in the gut microbiota. Urinary equol production had no significant correlation with vaginal microbiota, although it had significant relationships with gut microbiota in postmenopausal women. In both groups, the proportions of vaginal Lactobacillus were inversely correlated with vaginal microbial diversity and vaginal pH. Conclusion: Postmenopausal women had significantly low Lactobacillus and high nonoptimal species in their vaginal flora, whereas such age-related differences were not identified in gut microbiota. Urinary equol concentration had significant correlation with gut microbiota in postmenopausal women only. This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (Trial registration No.: UMIN000043944).

Development of the first fermented soy beverages enriched in equol and 5-hydroxy-equol

Daidzin and genistin, present in soy, can be transformed by the intestinal microbiota into equol and 5-hydroxy-equol; compounds beneficial to human health, although these compounds are only produced by a fraction of the population and in low concentrations. Hence, there is an interest in the ingestion of these compounds. Engineered lactic acid bacteria strains harbouring daidzein reductase, dihydrodaidzein reductase, tetrahydrodaidzein reductase and the dihydrodaidzein racemase genes from Slackia isoflavoniconvertens DSM22006 were incubated in five commercial soy beverages with strains with a high capacity to transform glycosylated isoflavones into their aglycones. High equol and 5-hydroxy-equol concentrations were produced in the five commercial soy beverages; the soy beverages from VegeDia and Carrefour being the ones that showed the highest concentrations of equol (456.02 ± 14.62 and 366.07 ± 25.81 μmol/L) and 5-hydroxy-equol (126.07 ± 6.23 and 121.00 ± 9.57 μmol/L). Moreover, dihydrodaidzein racemase and Bifidobacterium pseudocatenulatum INIA P815, with a high capacity to transform isoflavone glycosides into their aglycones, were necessary to achieve high equol and 5-hydroxy-equol concentrations. Bacteria generally recognized as safe produced the first fermented soy beverages enriched in equol and 5-hydroxy-equol. The high concentrations of these compounds attained in these beverages would have great potential for consumer health.

Estrogenic in vitro evaluation of zearalenone and its phase I and II metabolites in combination with soy isoflavones

Humans and animals are exposed to multiple substances in their food and feed that might have a negative health impact. Among these substances, the Fusarium mycoestrogen zearalenone (ZEN) and its metabolites α-zearalenol (α-ZEL) and α-zearalanol (α-ZAL) are known to possess endocrine disruptive properties. In a mixed diet or especially animal feed, these potential contaminants might be ingested together with naturally occurring phytoestrogens such as soy isoflavones. So far, risk assessment of potential endocrine disruptors is usually based on adverse effects of single compounds whereas studies investigating combinatorial effects are scarce. In the present study, we investigated the estrogenic potential of mycoestrogens and the isoflavones genistein (GEN), daidzein (DAI) and glycitein (GLY) as well as equol (EQ), the gut microbial metabolite of DAI, in vitro alone or in combination, using the alkaline phosphatase (ALP) assay in Ishikawa cells. In the case of mycoestrogens, the tested concentration range included 0.001 to 10 nM with multiplication steps of 10 in between, while for the isoflavones 1000 times higher concentrations were investigated. For the individual substances the following order of estrogenicity was obtained: α-ZEL > α-ZAL > ZEN > GEN > EQ > DAI > GLY. Most combinations of isoflavones with mycoestrogens enhanced the estrogenic response in the investigated concentrations. Especially lower concentrations of ZEN, α-ZEL and α-ZAL (0.001—0.01 nM) in combination with low concentrations of GEN, DAI and EQ (0.001—0.1 µM) strongly increased the estrogenic response compared to the single substances.

Association between equol production and metabolic syndrome in Japanese women in their 50s-60s.

Equol is an active metabolite of soy isoflavone. As a phytoestrogen, equol has the potential to prevent metabolic disorders such as hyperglycemia, hyperlipidemia, and obesity. This study aimed to determine the association between equol production and metabolic syndrome (METS) in postmenopausal women. This cross-sectional study included 1,345 women aged 50 to 69 years who underwent health checkups from February 2018 to November 2021 at four health centers in Fukushima, Japan. Equol producers were defined as those with a urinary equol concentration of 1.0 μM or more. METS was defined based on Japanese diagnostic criteria including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and glucose intolerance. The association between equol production and METS was estimated by logistic regression analysis, with adjustments for age, exercise, physical activity, and fast walking. Of the 1,345 women, 378 (28.1%) were equol producers. The proportion of women who had METS (6.6% vs 10.9%) was significantly lower in the equol-producing group than in the nonproducing group. Multivariable logistic regression analysis revealed that equol production was significantly associated with METS (odds ratio, 0.60; 95% CI, 0.38-0.95). Equol production was associated with a lower prevalence of METS among women aged 50 to 69 years.