Soy isoflavone-specific biotransformation product S-equol in the colon: physiological functions, transformation mechanisms, and metabolic regulatory pathways

Wang, Xiaoying; Chen, Baiyan; Fang, Xiang; Qin, Zhong; Liao, Zhenlin; Wang, Jie; Wu, Xuejiao; Ma, Yuhao; Li, Pengzhen; Feng, Xiaoxuan; Wang, Li

doi:10.1080/10408398.2022.2154744

Cited by 10 publications

(9 citation statements)

References 206 publications

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“…Isoflavones are commonly utilized as antioxidative dietary supplements. However, ( S )-equol, a secondary metabolite of isoflavone by the gut microbiota, exhibits significantly higher antioxidative capacity than its precursor [ 2 , 4 ]. Consequently, developing EcN strains with the ability to efficiently convert dietary isoflavones into ( S )-equol may represent an effective strategy to confer the ( S )-equol-producing phenotype of the host.…”

Section: Resultsmentioning

confidence: 99%

“…Its potential in alleviating oxidative stress, menopausal syndrome, cardiovascular disease, and osteoporosis, as well as reducing the risk of prostate, colon, and breast cancer, has garnered substantial clinical interest [ 2 , 3 ]. However, only a fraction (25 to 50%) of people harbor gut bacteria with an ( S )-equol-producing pathway capable of metabolizing dietary daidzein into ( S )-equol [ 4 , 5 ]. Fecal transplant therapy has demonstrated success in conferring an ( S )-equol-producing phenotype in hosts by providing them with exogenous gut bacteria expressing the necessary enzymes for daidzein conversion into ( S )-equol [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…The ( S )-equol-producing pathway involves four enzymatic steps: daidzein reductase (DZNR) catalyzes the conversion of daidzein to ( R )-dihydrodaidzein, which can further undergo conversion to ( S )-dihydrodaidzein facilitated by dihydrodaidzein racemase (DDRC) [ 3 , 4 ]. The subsequent reduction of ( S )-dihydrodaidzein to t -tetrahydrodaidzein occurs through dihydrodaidzein reductase (DHDR), followed by the transformation of t -tetrahydrodaidzein into ( S )-equol via tetrahydrodaidzein reductase (THDR) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Deciphering the Crucial Roles of the Quorum-Sensing Transcription Factor SdiA in NADPH Metabolism and (S)-Equol Production in Escherichia coli Nissle 1917

Wang,

Dai,

Azi

et al. 2024

Antioxidants

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The active metabolite (S)-equol, derived from daidzein by gut microbiota, exhibits superior antioxidative activity compared with its precursor and plays a vital role in human health. As only 25% to 50% of individuals can naturally produce equol when supplied with isoflavone, we engineered probiotic E. coli Nissle 1917 (EcN) to convert dietary isoflavones into (S)-equol, thus offering a strategy to mimic the gut phenotype of natural (S)-equol producers. However, co-fermentation of EcN-eq with fecal bacteria revealed that gut microbial metabolites decreased NADPH levels, hindering (S)-equol production. Transcriptome analysis showed that the quorum-sensing (QS) transcription factor SdiA negatively regulates NADPH levels and (S)-equol biosynthesis in EcN-eq. Screening AHLs showed that SdiA binding to C10-HSL negatively regulates the pentose phosphate pathway, reducing intracellular NADPH levels in EcN-eq. Molecular docking and dynamics simulations investigated the structural disparities in complexes formed by C10-HSL with SdiA from EcN or E. coli K12. Substituting sdiA_EcN in EcN-eq with sdiA_K12 increased the intracellular NADPH/NADP+ ratio, enhancing (S)-equol production by 47%. These findings elucidate the impact of AHL-QS in the gut microbiota on EcN NADPH metabolism, offering insights for developing (S)-equol-producing EcN probiotics tailored to the gut environment.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Deciphering the Crucial Roles of the Quorum-Sensing Transcription Factor SdiA in NADPH Metabolism and (S)-Equol Production in Escherichia coli Nissle 1917

Wang,

Dai,

Azi

et al. 2024

Antioxidants

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“…This type of metabolism that leaves the liver and re-enters the gut is call phase II metabolism. [17,18].…”

Section: Metabolism and Regulatory Mechanism Of Equolmentioning

confidence: 99%

Advances in the Metabolic Mechanism and Functional Characteristics of Equol

Gong

Pang

et al. 2023

Foods

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Equol is the most potent soy isoflavone metabolite and is produced by specific intestinal microorganisms of mammals. It has promising application possibilities for preventing chronic diseases such as cardiovascular disease, breast cancer, and prostate cancer due to its high antioxidant activity and hormone-like activity. Thus, it is of great significance to systematically study the efficient preparation method of equol and its functional activity. This paper elaborates on the metabolic mechanism of equol in humans; focuses on the biological characteristics, synthesis methods, and the currently isolated equol-producing bacteria; and looks forward to its future development and application direction, aiming to provide guidance for the application and promotion of equol in the field of food and health products.

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“…The main soy isoflavone, daidzein, is metabolized and absorbed by intestinal bacteria, and those who have intestinal bacteria capable of metabolizing to equol are defined as equol producers (EQP) [ 10 ]. EQPs have been reported to be associated with a lower risk of developing hormone-derived cancers, fewer menopausal symptoms, and less osteoporosis, among other health outcomes [ 12 ]. Several bacteria have been reported to be in intestinal microflora in EQPs, and their metabolism requires multiple bacteria [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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

Fujitani,

Lyu,

Sassa

et al. 2023

Environ. Health Prev. Med.

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Background 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). Methods 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. Results 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. Conclusions 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. Supplementary information The online version contains supplementary material available at https://doi.org/10.1265/ehpm.23-00148 .

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Soy isoflavone-specific biotransformation product S-equol in the colon: physiological functions, transformation mechanisms, and metabolic regulatory pathways

Cited by 10 publications

References 206 publications

Deciphering the Crucial Roles of the Quorum-Sensing Transcription Factor SdiA in NADPH Metabolism and (S)-Equol Production in Escherichia coli Nissle 1917

Deciphering the Crucial Roles of the Quorum-Sensing Transcription Factor SdiA in NADPH Metabolism and (S)-Equol Production in Escherichia coli Nissle 1917

Advances in the Metabolic Mechanism and Functional Characteristics of Equol

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

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