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

      research-article
      , , ,
      Environmental Health and Preventive Medicine
      Japanese Society for Hygiene
      Enterotype, Isoflavone, Metabolism, Zinc, Japanese

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          Abstract

          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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          Most cited references32

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          Mammalian zinc transporters: nutritional and physiologic regulation.

          Research advances defining how zinc is transported into and out of cells and organelles have increased exponentially within the past five years. Research has progressed through application of molecular techniques including genomic analysis, cell transfection, RNA interference, kinetic analysis of ion transport, and application of cell and animal models including knockout mice. The knowledge base has increased for most of 10 members of the ZnT family and 14 members of the Zrt-, Irt-like protein (ZIP) family. Relative to the handling of dietary zinc is the involvement of ZnT1, ZIP4, and ZIP5 in intestinal zinc transport, involvement of ZIP10 and ZnT1 in renal zinc reabsorption, and the roles of ZIP5, ZnT2, and ZnT1 in pancreatic release of endogenous zinc. These events are major factors in regulation of zinc homeostasis. Other salient findings are the involvement of ZnT2 in lactation, ZIP14 in the hypozincemia of inflammation, ZIP6, ZIP7, and ZIP10 in metastatic breast cancer, and ZnT8 in insulin processing and as an autoantigen in diabetes.
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            Zinc homeostasis and signaling in health and diseases

            The essential trace element zinc (Zn) is widely required in cellular functions, and abnormal Zn homeostasis causes a variety of health problems that include growth retardation, immunodeficiency, hypogonadism, and neuronal and sensory dysfunctions. Zn homeostasis is regulated through Zn transporters, permeable channels, and metallothioneins. Recent studies highlight Zn’s dynamic activity and its role as a signaling mediator. Zn acts as an intracellular signaling molecule, capable of communicating between cells, converting extracellular stimuli to intracellular signals, and controlling intracellular events. We have proposed that intracellular Zn signaling falls into two classes, early and late Zn signaling. This review addresses recent findings regarding Zn signaling and its role in physiological processes and pathogenesis.
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              • Abstract: found
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              Is Open Access

              Equol: A Bacterial Metabolite from The Daidzein Isoflavone and Its Presumed Beneficial Health Effects

              Epidemiological data suggest that regular intake of isoflavones from soy reduces the incidence of estrogen-dependent and aging-associated disorders, such as menopause symptoms in women, osteoporosis, cardiovascular diseases and cancer. Equol, produced from daidzein, is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. Consequently, equol has been endorsed as having many beneficial effects on human health. The conversion of daidzein into equol takes place in the intestine via the action of reductase enzymes belonging to incompletely characterized members of the gut microbiota. While all animal species analyzed so far produce equol, only between one third and one half of human subjects (depending on the community) are able to do so, ostensibly those that harbor equol-producing microbes. Conceivably, these subjects might be the only ones who can fully benefit from soy or isoflavone consumption. This review summarizes current knowledge on the microorganisms involved in, the genetic background to, and the biochemical pathways of, equol biosynthesis. It also outlines the results of recent clinical trials and meta-analyses on the effects of equol on different areas of human health and discusses briefly its presumptive mode of action.
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                Author and article information

                Contributors
                kharada-hes@umin.ac.jp
                Journal
                Environ Health Prev Med
                Environ Health Prev Med
                EHPM
                Environmental Health and Preventive Medicine
                Japanese Society for Hygiene
                1342-078X
                1347-4715
                27 October 2023
                2023
                : 28
                : 63
                Affiliations
                [01]Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
                Author information
                http://orcid.org/0000-0001-7319-123X
                Article
                23-00148 ehpm-28-063
                10.1265/ehpm.23-00148
                10613555
                37899210
                05c069f0-8b1b-48a1-9097-4cf380b8655b
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 12 June 2023
                : 30 September 2023
                Page count
                Pages: 6
                Categories
                Research Article

                Occupational & Environmental medicine
                enterotype,isoflavone,metabolism,zinc,japanese
                Occupational & Environmental medicine
                enterotype, isoflavone, metabolism, zinc, japanese

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