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Hu J, Mesnage R, Tuohy K, Heiss C, Rodriguez-Mateos A. (Poly)phenol-related gut metabotypes and human health: an update. Food Funct 2024; 15:2814-2835. [PMID: 38414364 DOI: 10.1039/d3fo04338j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
Dietary (poly)phenols have received great interest due to their potential role in the prevention and management of non-communicable diseases. In recent years, a high inter-individual variability in the biological response to (poly)phenols has been demonstrated, which could be related to the high variability in (poly)phenol gut microbial metabolism existing within individuals. An interplay between (poly)phenols and the gut microbiota exists, with (poly)phenols being metabolised by the gut microbiota and their metabolites modulating gut microbiota diversity and composition. A number of (poly)phenol metabolising phenotypes or metabotypes have been proposed, however, potential metabotypes for most (poly)phenols have not been investigated, and the relationship between metabotypes and human health remains ambiguous. This review presents updated knowledge on the reciprocal interaction between (poly)phenols and the gut microbiome, associated gut metabotypes, and subsequent impact on human health.
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Affiliation(s)
- Jiaying Hu
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
| | - Robin Mesnage
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
- Buchinger Wilhelmi Clinic, Überlingen, Germany
| | - Kieran Tuohy
- School of Food Science and Nutrition, Faculty of Environment, University of Leeds, Leeds, UK
| | - Christian Heiss
- Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
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Schmidt HC, Hagens J, Schuppert P, Appl B, Raluy LP, Trochimiuk M, Philippi C, Li Z, Reinshagen K, Tomuschat C. Biliatresone induces cholangiopathy in C57BL/6J neonates. Sci Rep 2023; 13:10574. [PMID: 37386088 PMCID: PMC10310722 DOI: 10.1038/s41598-023-37354-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 06/20/2023] [Indexed: 07/01/2023] Open
Abstract
Exposure to plant toxins or microbiota that are able to digest common food ingredients to toxic structures might be responsible for biliary atresia (BA). An isoflavonoid, biliatresone is known to effectively alter the extrahepatic bile duct (EHBD) development in BALB/c mice. Biliatresone causes a reduction of Glutathione (GSH) levels, SOX17 downregulation and is effectively countered with N-Acetyl-L-cysteine treatment in vitro. Therefore, reversing GSH-loss appears to be a promising treatment target for a translational approach. Since BALB/c mice have been described as sensitive in various models, we evaluated the toxic effect of biliatresone in robust C57BL/6J mice and confirmed its toxicity. Comparison between BALB/c and C57BL/6J mice revealed similarity in the toxic model. Affected neonates exhibited clinical symptoms of BA, such as jaundice, ascites, clay-colored stools, yellow urine and impaired weight gain. The gallbladders of jaundiced neonates were hydropic and EHBD were twisted and enlarged. Serum and histological analysis proved cholestasis. No anomalies were seen in the liver and EHBD of control animals. With our study we join a chain of evidence confirming that biliatresone is an effective agent for cross-lineage targeted alteration of the EHBD system.
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Affiliation(s)
- Hans Christian Schmidt
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
| | - Johanna Hagens
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Pauline Schuppert
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Birgit Appl
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Laia Pagerols Raluy
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Magdalena Trochimiuk
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Clara Philippi
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Zhongwen Li
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Konrad Reinshagen
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Christian Tomuschat
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
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Gong Y, Lv J, Pang X, Zhang S, Zhang G, Liu L, Wang Y, Li C. Advances in the Metabolic Mechanism and Functional Characteristics of Equol. Foods 2023; 12:2334. [PMID: 37372545 DOI: 10.3390/foods12122334] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/07/2023] [Accepted: 06/08/2023] [Indexed: 06/29/2023] Open
Abstract
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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Affiliation(s)
- Yining Gong
- Key Laboratory of Dairy Sciences, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin 150030, China
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No. 2 Yuan Ming Yuan West Road, Beijing 100193, China
| | - Jiaping Lv
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No. 2 Yuan Ming Yuan West Road, Beijing 100193, China
| | - Xiaoyang Pang
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No. 2 Yuan Ming Yuan West Road, Beijing 100193, China
| | - Shuwen Zhang
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No. 2 Yuan Ming Yuan West Road, Beijing 100193, China
| | - Guofang Zhang
- Key Laboratory of Dairy Sciences, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Libo Liu
- Key Laboratory of Dairy Sciences, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Yunna Wang
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No. 2 Yuan Ming Yuan West Road, Beijing 100193, China
| | - Chun Li
- Key Laboratory of Dairy Sciences, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Green Food Science Research Institute, Harbin 150030, China
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Soukup ST, Engelbert AK, Watzl B, Bub A, Kulling SE. Microbial Metabolism of the Soy Isoflavones Daidzein and Genistein in Postmenopausal Women: Human Intervention Study Reveals New Metabotypes. Nutrients 2023; 15:nu15102352. [PMID: 37242235 DOI: 10.3390/nu15102352] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/05/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND Soy isoflavones belong to the group of phytoestrogens and are associated with beneficial health effects but are also discussed to have adverse effects. Isoflavones are intensively metabolized by the gut microbiota leading to metabolites with altered estrogenic potency. The population is classified into different isoflavone metabotypes based on individual metabolite profiles. So far, this classification was based on the capacity to metabolize daidzein and did not reflect genistein metabolism. We investigated the microbial metabolite profile of isoflavones considering daidzein and genistein. METHODS Isoflavones and metabolites were quantified in the urine of postmenopausal women receiving a soy isoflavone extract for 12 weeks. Based on these data, women were clustered in different isoflavone metabotypes. Further, the estrogenic potency of these metabotypes was estimated. RESULTS Based on the excreted urinary amounts of isoflavones and metabolites, the metabolite profiles could be calculated, resulting in 5 metabotypes applying a hierarchical cluster analysis. The metabotypes differed in part strongly regarding their metabolite profile and their estimated estrogenic potency.
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Affiliation(s)
- Sebastian T Soukup
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Straße 9, 76131 Karlsruhe, Germany
| | - Ann Katrin Engelbert
- Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Straße 9, 76131 Karlsruhe, Germany
| | - Bernhard Watzl
- Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Straße 9, 76131 Karlsruhe, Germany
| | - Achim Bub
- Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Straße 9, 76131 Karlsruhe, Germany
| | - Sabine E Kulling
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Straße 9, 76131 Karlsruhe, Germany
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Zhu JJ, Yang YF, Dong R, Zheng S. Biliatresone: progress in biliary atresia study. World J Pediatr 2023; 19:417-424. [PMID: 36166189 PMCID: PMC10149470 DOI: 10.1007/s12519-022-00619-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 09/05/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND Biliary atresia (BA) is one of the main causes of neonatal end-stage liver disease. Without timely diagnosis and treatment, most children with BA will develop irreversible liver fibrosis within the first two months. While current theorized causes of BA include viral infection, immune disorders, and genetic defects, the comprehensive etiology is still largely unknown. Recently, biliatresone attracted much interest for its ability to induce BA in both zebrafish and mice, so we summarized the latest progress of biliatresone research in BA and tried to answer the question of whether it could provide further clues to the etiology of human BA. DATA SOURCES We conducted a PubMed search for any published articles related to the topic using search terms including "biliary atresia", "biliatresone", "GSH", and "HSP90". Relevant data were extracted from the original text or supplementary materials of the corresponding articles. RESULTS Biliatresone had shown its unique toxicity in multiple species such as zebrafish and mice, and pathogenic factors involved included glutathione (GSH), heat shock protein 90 (HSP90) and the related pathways. In combination with epidemiological evidence and recent studies on the intestinal flora in biliary atresia, a new pathogenic hypothesis that the occurrence of biliary atresia is partly due to biliatresone or its structure-like compounds depositing in human body via vegetables or/and the altered intestinal flora structure can be tentatively established. CONCLUSIONS Based on the existing evidence, we emphasized that GSH and HSP90 are involved in the development of BA, and the maternal diet, especially higher vegetable intake of Asian women of childbearing age, accompanied by the altered intestinal flora structure, may contribute to the occurrence of biliary atresia and the higher incidence in the Asia group. However, the evidence from large sample epidemiological research is necessary.
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Affiliation(s)
- Jia-Jie Zhu
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Yi-Fan Yang
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Rui Dong
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Shan Zheng
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
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Zhang Y, Yu W, Zhang L, Wang M, Chang W. The Interaction of Polyphenols and the Gut Microbiota in Neurodegenerative Diseases. Nutrients 2022; 14:nu14245373. [PMID: 36558531 PMCID: PMC9785743 DOI: 10.3390/nu14245373] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/13/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022] Open
Abstract
Polyphenols are secondary metabolites of plants and play a potential role in the prevention and treatment of neurodegenerative diseases (NND) such as Alzheimer's disease (AD) and Parkinson's disease (PD) due to their unique physiological functions such as acting as antioxidants, being anti-inflammatory, being neuroprotective, and promoting intestinal health. Since dietary polyphenols exist in plant foods in the form of glycosylation or esterification or are combined with polymers, they need to undergo extensive metabolism through phase I and phase II biotransformations by various intestinal enzymes, as well as metabolism by the intestinal microbiota before they can be fully absorbed. Polyphenols improve intestinal microbiota disorders by influencing the structure and function of intestinal microbiota, inducing beneficial bacteria to produce a variety of metabolites such as short-chain fatty acids (SCFAs), promoting the secretion of hormones and neurotransmitters, and playing an important role in the prevention and treatment of NND by affecting the microbe-gut-brain axis. We review the ways in which some polyphenols can change the composition of the intestinal microbiota and their metabolites in AD or PD animal models to exert the role of slowing down the progression of NND, aiming to provide evidence for the role of polyphenols in slowing the progression of NND via the microbiota-gut-brain (MGB) axis.
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Affiliation(s)
- Yuan Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China
- Correspondence: ; Tel.: +86-532-82991791
| | - Wanpeng Yu
- Medical College, Qingdao University, Qingdao 266021, China
| | - Lei Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China
| | - Man Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China
| | - Wenguang Chang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China
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Sgro M, Iacono G, Yamakawa GR, Kodila ZN, Marsland BJ, Mychasiuk R. Age matters: Microbiome depletion prior to repeat mild traumatic brain injury differentially alters microbial composition and function in adolescent and adult rats. PLoS One 2022; 17:e0278259. [PMID: 36449469 PMCID: PMC9710846 DOI: 10.1371/journal.pone.0278259] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 11/13/2022] [Indexed: 12/02/2022] Open
Abstract
Dysregulation of the gut microbiome has been shown to perpetuate neuroinflammation, alter intestinal permeability, and modify repetitive mild traumatic brain injury (RmTBI)-induced deficits. However, there have been no investigations regarding the comparative effects that the microbiome may have on RmTBI in adolescents and adults. Therefore, we examined the influence of microbiome depletion prior to RmTBI on microbial composition and metabolome, in adolescent and adult Sprague Dawley rats. Rats were randomly assigned to standard or antibiotic drinking water for 14 days, and to subsequent sham or RmTBIs. The gut microbiome composition and metabolome were analysed at baseline, 1 day after the first mTBI, and at euthanasia (11 days following the third mTBI). At euthanasia, intestinal samples were also collected to quantify tight junction protein (TJP1 and occludin) expression. Adolescents were significantly more susceptible to microbiome depletion via antibiotic administration which increased pro-inflammatory composition and metabolites. Furthermore, RmTBI induced a transient increase in 'beneficial bacteria' (Lachnospiraceae and Faecalibaculum) in only adolescents that may indicate compensatory action in response to the injury. Finally, microbiome depletion prior to RmTBI generated a microbiome composition and metabolome that exemplified a potentially chronic pathogenic and inflammatory state as demonstrated by increased Clostridium innocuum and Erysipelatoclostridium and reductions in Bacteroides and Clostridium Sensu Stricto. Results highlight that adolescents are more vulnerable to RmTBI compared to adults and dysbiosis prior to injury may exacerbate secondary inflammatory cascades.
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Affiliation(s)
- Marissa Sgro
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Giulia Iacono
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Glenn R. Yamakawa
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Zoe N. Kodila
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Benjamin J. Marsland
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Richelle Mychasiuk
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia
- * E-mail:
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Metabolomics profiles of premenopausal women are different based on O-desmethylangolensin metabotype. Br J Nutr 2022; 128:1490-1498. [PMID: 34763731 PMCID: PMC9095764 DOI: 10.1017/s0007114521004463] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Urinary O-desmethylangolensin (ODMA) concentrations provide a functional gut microbiome marker of dietary isoflavone daidzein metabolism to ODMA. Individuals who do not have gut microbial environments that produce ODMA have less favourable cardiometabolic and cancer risk profiles. Urinary metabolomics profiles were evaluated in relation to ODMA metabotypes within and between individuals over time. Secondary analysis of data was conducted from the BEAN2 trial, which was a cross-over study of premenopausal women consuming 6 months on a high and a low soya diet, each separated by a 1-month washout period. In all of the 672 samples in the study, sixty-six of the eighty-four women had the same ODMA metabotype at seven or all eight time points. Two or four urine samples per woman were selected based on temporal metabotypes in order to compare within and across individuals. Metabolomics assays for primary metabolism and biogenic amines were conducted in sixty urine samples from twenty women. Partial least-squares discriminant analysis was used to compare metabolomics profiles. For the same ODMA metabotype across different time points, no profile differences were detected. For changes in metabotype within individuals and across individuals with different metabotypes, distinct metabolomes emerged. Influential metabolites (variables importance in projection score > 2) included several phenolic compounds, carnitine and derivatives, fatty acid and amino acid metabolites and some medications. Based on the distinct metabolomes of producers v. non-producers, the ODMA metabotype may be a marker of gut microbiome functionality broadly involved in nutrient and bioactive metabolism and should be evaluated for relevance to precision nutrition initiatives.
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Zhao Y, Zhong X, Yan J, Sun C, Zhao X, Wang X. Potential roles of gut microbes in biotransformation of natural products: An overview. Front Microbiol 2022; 13:956378. [PMID: 36246222 PMCID: PMC9560768 DOI: 10.3389/fmicb.2022.956378] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 08/29/2022] [Indexed: 11/23/2022] Open
Abstract
Natural products have been extensively applied in clinical practice, characterized by multi-component and multi-target, many pharmacodynamic substances, complex action mechanisms, and various physiological activities. For the oral administration of natural products, the gut microbiota and clinical efficacy are closely related, but this relationship remains unclear. Gut microbes play an important role in the transformation and utilization of natural products caused by the diversity of enzyme systems. Effective components such as flavonoids, alkaloids, lignans, and phenols cannot be metabolized directly through human digestive enzymes but can be transformed by enzymes produced by gut microorganisms and then utilized. Therefore, the focus is paid to the metabolism of natural products through the gut microbiota. In the present study, we systematically reviewed the studies about gut microbiota and their effect on the biotransformation of various components of natural products and highlighted the involved common bacteria, reaction types, pharmacological actions, and research methods. This study aims to provide theoretical support for the clinical application in the prevention and treatment of diseases and provide new ideas for studying natural products based on gut biotransformation.
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Affiliation(s)
- Yucui Zhao
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xinqin Zhong
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Junyuan Yan
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Congying Sun
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xin Zhao
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Xin Zhao,
| | - Xiaoying Wang
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Xiaoying Wang,
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10
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Scott MB, Styring AK, McCullagh JSO. Polyphenols: Bioavailability, Microbiome Interactions and Cellular Effects on Health in Humans and Animals. Pathogens 2022; 11:770. [PMID: 35890016 PMCID: PMC9324685 DOI: 10.3390/pathogens11070770] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 06/26/2022] [Accepted: 07/03/2022] [Indexed: 12/12/2022] Open
Abstract
Polyphenolic compounds have a variety of functions in plants including protecting them from a range of abiotic and biotic stresses such as pathogenic infections, ionising radiation and as signalling molecules. They are common constituents of human and animal diets, undergoing extensive metabolism by gut microbiota in many cases prior to entering circulation. They are linked to a range of positive health effects, including anti-oxidant, anti-inflammatory, antibiotic and disease-specific activities but the relationships between polyphenol bio-transformation products and their interactions in vivo are less well understood. Here we review the state of knowledge in this area, specifically what happens to dietary polyphenols after ingestion and how this is linked to health effects in humans and animals; paying particular attention to farm animals and pigs. We focus on the chemical transformation of polyphenols after ingestion, through microbial transformation, conjugation, absorption, entry into circulation and uptake by cells and tissues, focusing on recent findings in relation to bone. We review what is known about how these processes affect polyphenol bioactivity, highlighting gaps in knowledge. The implications of extending the use of polyphenols to treat specific pathogenic infections and other illnesses is explored.
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Affiliation(s)
- Michael B. Scott
- Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK;
- School of Archaeology, University of Oxford, Oxford OX1 3TG, UK;
| | - Amy K. Styring
- School of Archaeology, University of Oxford, Oxford OX1 3TG, UK;
| | - James S. O. McCullagh
- Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK;
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11
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Landete JM. Development of soy beverages enriched in O-desmethylangolesin and 6-hydroxy-O-desmethylangolesin by engineered lactic acid bacteria. Lebensm Wiss Technol 2022. [DOI: 10.1016/j.lwt.2022.113526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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12
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Maximizing the Estrogenic Potential of Soy Isoflavones through the Gut Microbiome: Implication for Cardiometabolic Health in Postmenopausal Women. Nutrients 2022; 14:nu14030553. [PMID: 35276910 PMCID: PMC8840243 DOI: 10.3390/nu14030553] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 01/17/2022] [Accepted: 01/21/2022] [Indexed: 12/24/2022] Open
Abstract
Soy isoflavones have been suggested as an alternative treatment for managing postmenopausal symptoms and promoting long-term health due to their structural similarity to mammalian estrogen and ability to bind to estrogen receptors. Among all soy isoflavones and their metabolites, (S)-equol is known for having the strongest estrogenic activity. Equol is a metabolite of the soy isoflavone daidzein produced through intestinal bacterial metabolism. However, more than half of the human population is not able to produce equol due to the lack of equol-producing bacteria in their gastrointestinal tract. The interpersonal variations in the gut microbiome complicate the interpretation of data collected from humans. Furthermore, because rodents are efficient equol-producers, translatability between rodent models and humans is challenging. Herein, we first summarized the current knowledge of the microbial conversion of daidzein to equol, its relation to health, and proposed the need for developing model systems by which equol production can be manipulated while controlling other known confounding factors. Determining the necessity of equol-producing capacity within a gut microbial community when consuming soy as a functional ingredient, and identifying strategies to maximize equol production by modulating the gut microbiome, may provide future therapeutic approaches to improve the health of postmenopausal women.
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Osborn LJ, Claesen J, Brown JM. Microbial Flavonoid Metabolism: A Cardiometabolic Disease Perspective. Annu Rev Nutr 2021; 41:433-454. [PMID: 34633856 DOI: 10.1146/annurev-nutr-120420-030424] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Cardiometabolic disease (CMD) is a leading cause of death worldwide and encompasses the inflammatory metabolic disorders of obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. Flavonoids are polyphenolic plant metabolites that are abundantly present in fruits and vegetables and have biologically relevant protective effects in a number of cardiometabolic disorders. Several epidemiological studies underscored a negative association between dietary flavonoid consumption and the propensity to develop CMD. Recent studies elucidated the contribution of the gut microbiota in metabolizing dietary intake as it relates to CMD. Importantly, the biological efficacy of flavonoids in humans and animal models alike is linked to the gut microbial community. Herein, we discuss the opportunities and challenges of leveraging flavonoid intake as a potential strategy to prevent and treat CMD in a gut microbe-dependent manner, with special emphasis on flavonoid-derived microbial metabolites.
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Affiliation(s)
- Lucas J Osborn
- Department of Cardiovascular and Metabolic Sciences and Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio 44195, USA; , , .,Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
| | - Jan Claesen
- Department of Cardiovascular and Metabolic Sciences and Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio 44195, USA; , , .,Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
| | - J Mark Brown
- Department of Cardiovascular and Metabolic Sciences and Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio 44195, USA; , , .,Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
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14
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Fujitani T, Fujii Y, Lyu Z, Harada Sassa M, Harada KH. Urinary equol levels are positively associated with urinary estradiol excretion in women. Sci Rep 2021; 11:19532. [PMID: 34593903 PMCID: PMC8484452 DOI: 10.1038/s41598-021-98872-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 09/16/2021] [Indexed: 11/09/2022] Open
Abstract
Isoflavones found in soy products are a promising class of nutrients that may have a positive effect on human health. In particular, the phytoestrogen metabolite equol is associated with a reduced risk of developing female hormone-related diseases. However, the effect of equol on estrogen remains unclear. Equol can modify blood and urinary estradiol (E2) levels. The aim of this cross-sectional study was to examine the associations between urinary estrogen levels, equol levels, and equol production status in Japanese women. We analyzed urine samples from 520 women by gas chromatography-mass spectrometry. Urinary E2 and 4-hydroxylated E2 levels were higher in equol producers (EQP) than in non-EQPs (P < 0.0001 and P=0.00112, respectively). After adjusting for age and tobacco use by analysis of covariance, the association remained significant (β = 0.299, P < 0.0001). Analysis of covariance demonstrated that equol levels in urine were also positively associated with urinary E2 (β = 0.597, P < 0.0001). The log equol concentration showed a significant, but moderate, negative association with the serum E2 concentration (β = − 0.0225, P = 0.0462). Our findings suggest that equol may promote urinary E2 excretion and modify blood E2 levels in women.
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Affiliation(s)
- Tomoko Fujitani
- Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan
| | - Yukiko Fujii
- Department of Pharmaceutical Sciences, Daiichi University of Pharmacy, Fukuoka, 815-8511, Japan
| | - Zhaoqing Lyu
- Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan
| | - Mariko Harada Sassa
- Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan
| | - Kouji H Harada
- Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
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15
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Aboushanab SA, Khedr SM, Gette IF, Danilova IG, Kolberg NA, Ravishankar GA, Ambati RR, Kovaleva EG. Isoflavones derived from plant raw materials: bioavailability, anti-cancer, anti-aging potentials, and microbiome modulation. Crit Rev Food Sci Nutr 2021; 63:261-287. [PMID: 34251921 DOI: 10.1080/10408398.2021.1946006] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Isoflavones are secondary metabolites that represent the most abundant category of plant polyphenols. Dietary soy, kudzu, and red clover contain primarily genistein, daidzein, glycitein, puerarin, formononetin, and biochanin A. The structural similarity of these compounds to β-estradiol has demonstrated protection against age-related and hormone-dependent diseases in both genders. Demonstrative shreds of evidence confirmed the fundamental health benefits of the consumption of these isoflavones. These relevant activities are complex and largely driven by the source, active ingredients, dose, and administration period of the bioactive compounds. However, the preclinical and clinical studies of these compounds are greatly variable, controversial, and still with no consensus due to the non-standardized research protocols. In addition, absorption, distribution, metabolism, and excretion studies, and the safety profile of isoflavones have been far limited. This highlights a major gap in understanding the potentially critical role of these isoflavones as prospective replacement therapy. Our general review exclusively focuses attention on the crucial role of isoflavones derived from these plant materials and critically highlights their bioavailability, possible anticancer, antiaging potentials, and microbiome modulation. Despite their fundamental health benefits, plant isoflavones reveal prospective therapeutic effects that worth further standardized analysis.
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Affiliation(s)
- Saied A Aboushanab
- Institute of Chemical Engineering, Ural Federal University named after the first President of Russia B. N. Yeltsin, Yekaterinburg, Russia
| | - Shaimaa M Khedr
- Pharmaceutical and Fermentation Industries Development Center (PFIDC), City of Scientific Research and Technological Applications, SRTA-City, Alexandria, Egypt
| | - Irina F Gette
- Institute of Chemical Engineering, Ural Federal University named after the first President of Russia B. N. Yeltsin, Yekaterinburg, Russia.,Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia
| | - Irina G Danilova
- Institute of Chemical Engineering, Ural Federal University named after the first President of Russia B. N. Yeltsin, Yekaterinburg, Russia.,Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia
| | - Natalia A Kolberg
- Integrated Laboratory Complex, Ural State University of Economics, Yekaterinburg, Russia
| | - Gokare A Ravishankar
- C. D. Sagar Centre for Life Sciences, Dayananda Sagar College of Engineering, Dayananda Sagar Institutions, Bangalore, Karnataka, India
| | - Ranga Rao Ambati
- Department of Biotechnology, Vignan's Foundation of Science, Technology and Research, Guntur, Andhra Pradesh, India
| | - Elena G Kovaleva
- Institute of Chemical Engineering, Ural Federal University named after the first President of Russia B. N. Yeltsin, Yekaterinburg, Russia
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16
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Li Q, Gao B, Siqin B, He Q, Zhang R, Meng X, Zhang N, Zhang N, Li M. Gut Microbiota: A Novel Regulator of Cardiovascular Disease and Key Factor in the Therapeutic Effects of Flavonoids. Front Pharmacol 2021; 12:651926. [PMID: 34220497 PMCID: PMC8241904 DOI: 10.3389/fphar.2021.651926] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 04/23/2021] [Indexed: 01/30/2023] Open
Abstract
Cardiovascular disease is the main cause of death worldwide, and traditional cardiovascular risk factors cannot fully explain the occurrence of the disease. In recent years, the relationship between gut microbiota and its metabolites and cardiovascular disease has been a hot study topic. The changes in gut microbiota and its metabolites are related to the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. The mechanisms by which gut microbiota and its metabolites influence cardiovascular disease have been reported, although not comprehensively. Additionally, following ingestion, flavonoids are decomposed into phenolic acids that are more easily absorbed by the body after being processed by enzymes produced by intestinal microorganisms, which increases flavonoid bioavailability and activity, consequently affecting the onset of cardiovascular disease. However, flavonoids can also inhibit the growth of harmful microorganisms, promote the proliferation of beneficial microorganisms, and maintain the balance of gut microbiota. Hence, it is important to study the relationship between gut microbiota and flavonoids to elucidate the protective effects of flavonoids in cardiovascular diseases. This article will review the role and mechanism of gut microbiota and its metabolites in the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. It also discusses the potential value of flavonoids in the prevention and treatment of cardiovascular disease following their transformation through gut microbiota metabolism.
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Affiliation(s)
- Qinyu Li
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Bing Gao
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Bateer Siqin
- Xilinguole Meng Mongolian General Hospital, Xilinhaote, China
| | - Qian He
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Ru Zhang
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Xiangxi Meng
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Naiheng Zhang
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Na Zhang
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Minhui Li
- Department of Pharmacy, Baotou Medical College, Baotou, China
- Pharmaceutical Laboratory, Inner Mongolia Institute of Traditional Chinese Medicine, Hohhot, China
- Inner Mongolia Key Laboratory of Characteristic Geoherbs Resources and Utilization, Baotou Medical College, Baotou, China
- Office of Academic Research, Qiqihar Medical University, Qiqihar, China
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17
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An Overview on Dietary Polyphenols and Their Biopharmaceutical Classification System (BCS). Int J Mol Sci 2021; 22:ijms22115514. [PMID: 34073709 PMCID: PMC8197262 DOI: 10.3390/ijms22115514] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 05/18/2021] [Accepted: 05/20/2021] [Indexed: 12/12/2022] Open
Abstract
Polyphenols are natural organic compounds produced by plants, acting as antioxidants by reacting with ROS. These compounds are widely consumed in daily diet and many studies report several benefits to human health thanks to their bioavailability in humans. However, the digestion process of phenolic compounds is still not completely clear. Moreover, bioavailability is dependent on the metabolic phase of these compounds. The LogP value can be managed as a simplified measure of the lipophilicity of a substance ingested within the human body, which affects resultant absorption. The biopharmaceutical classification system (BCS), a method used to classify drugs intended for gastrointestinal absorption, correlates the solubility and permeability of the drug with both the rate and extent of oral absorption. BCS may be helpful to measure the bioactive constituents of foods, such as polyphenols, in order to understand their nutraceutical potential. There are many literature studies that focus on permeability, absorption, and bioavailability of polyphenols and their resultant metabolic byproducts, but there is still confusion about their respective LogP values and BCS classification. This review will provide an overview of the information regarding 10 dietarypolyphenols (ferulic acid, chlorogenic acid, rutin, quercetin, apigenin, cirsimaritin, daidzein, resveratrol, ellagic acid, and curcumin) and their association with the BCS classification.
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18
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Guo Y, Zhao L, Fang X, Zhong Q, Liang H, Liang W, Wang L. Isolation and identification of a human intestinal bacterium capable of daidzein conversion. FEMS Microbiol Lett 2021; 368:6261181. [PMID: 33930123 DOI: 10.1093/femsle/fnab046] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 04/28/2021] [Indexed: 12/21/2022] Open
Abstract
Equol, which produced from daidzein (one of the principal isoflavones), is recognized to be the most resultful in stimulating an estrogenic and antioxidant response. The daidzein transformation was studied during fermentation of five growth media inoculated with feces from a healthy human, and a daidzein conversion strain was isolated. To enrich the bacterial population involved in daidzein metabolism in a complex mixture, fecal samples were treated with antibiotics. The improved propidium monoazide combined with the quantitative polymerase chain reaction (PMAxx-qPCR) assay showed that the ampicillin treatment of samples did result in a reduction of the total visible bacteria counts by 52.2% compared to the treatment without antibiotics. On this basis, the newly isolated rod-shaped, Gram-positive anaerobic bacterium, named strain Y11 (MN560033), was able to metabolize daidzein to equol under anaerobic conditions, with a conversion ratio (equol ratio: the amount of equol produced/amount of supplemented daizein) of 0.56 over 120 h. The 16S rRNA partial sequence of the strain Y11 exhibited 99.8% identity to that of Slackia equolifaciens strain DZE (NR116295). This study will provide new insights into the biotransformation of equol from daidzein by intestinal microbiota from the strain-level and explore the possibility of probiotic interventions.
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Affiliation(s)
- Yingyu Guo
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Lichao Zhao
- College of Food Science, South China Agricultural University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, China
| | - Xiang Fang
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Qingping Zhong
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Huijun Liang
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Wenou Liang
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Li Wang
- College of Food Science, South China Agricultural University, Guangzhou, China
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19
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Makarewicz M, Drożdż I, Tarko T, Duda-Chodak A. The Interactions between Polyphenols and Microorganisms, Especially Gut Microbiota. Antioxidants (Basel) 2021; 10:188. [PMID: 33525629 PMCID: PMC7911950 DOI: 10.3390/antiox10020188] [Citation(s) in RCA: 149] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/15/2021] [Accepted: 01/25/2021] [Indexed: 02/07/2023] Open
Abstract
This review presents the comprehensive knowledge about the bidirectional relationship between polyphenols and the gut microbiome. The first part is related to polyphenols' impacts on various microorganisms, especially bacteria, and their influence on intestinal pathogens. The research data on the mechanisms of polyphenol action were collected together and organized. The impact of various polyphenols groups on intestinal bacteria both on the whole "microbiota" and on particular species, including probiotics, are presented. Moreover, the impact of polyphenols present in food (bound to the matrix) was compared with the purified polyphenols (such as in dietary supplements) as well as polyphenols in the form of derivatives (such as glycosides) with those in the form of aglycones. The second part of the paper discusses in detail the mechanisms (pathways) and the role of bacterial biotransformation of the most important groups of polyphenols, including the production of bioactive metabolites with a significant impact on the human organism (both positive and negative).
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Affiliation(s)
| | | | | | - Aleksandra Duda-Chodak
- Department of Fermentation Technology and Microbiology, Faculty of Food Technology, University of Agriculture in Krakow, 30-149 Kraków, Poland; (M.M.); (I.D.); (T.T.)
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20
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Chen BD, Jia XM, Xu JY, Zhao LD, Ji JY, Wu BX, Ma Y, Li H, Zuo XX, Pan WY, Wang XH, Ye S, Tsokos GC, Wang J, Zhang X. An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus. Arthritis Rheumatol 2020; 73:232-243. [PMID: 33124780 DOI: 10.1002/art.41511] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/09/2020] [Accepted: 08/27/2020] [Indexed: 12/30/2022]
Abstract
OBJECTIVE Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in-depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE. METHODS Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole-genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single-nucleotide polymorphism-based strain-level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides. RESULTS Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA-442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE-enriched species. CONCLUSION This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen-mimicking peptides. Our data demonstrate that microbiome-altering approaches may offer valuable adjuvant therapies in SLE.
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Affiliation(s)
- Bei-di Chen
- Department of Rheumatology, Clinical Immunology Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, and Peking Union Medical College, Beijing, China
| | - Xin-Miao Jia
- Department of Rheumatology, Clinical Immunology Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, and Peking Union Medical College, Beijing, China
| | - Jia-Yue Xu
- Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China
| | - Li-Dan Zhao
- Department of Rheumatology, Clinical Immunology Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, and Peking Union Medical College, Beijing, China
| | | | - Bing-Xuan Wu
- Department of Rheumatology, Clinical Immunology Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, and Peking Union Medical College, Beijing, China
| | - Yue Ma
- Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China
| | - Hao Li
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Xiao-Xia Zuo
- Xiangya Hospital and Central South University, Changsha, China
| | - Wen-You Pan
- Huaian First People's Hospital and Nanjing Medical University, Huaian, China
| | | | - Shuang Ye
- Renji Hospital and Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - George C Tsokos
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Jun Wang
- Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China
| | - Xuan Zhang
- Department of Rheumatology, Clinical Immunology Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, and Peking Union Medical College, Beijing, China
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21
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Jaskiw GE, Obrenovich ME, Kundrapu S, Donskey CJ. Changes in the Serum Metabolome of Patients Treated With Broad-Spectrum Antibiotics. Pathog Immun 2020; 5:382-418. [PMID: 33474520 PMCID: PMC7810407 DOI: 10.20411/pai.v5i1.394] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 10/16/2020] [Indexed: 12/14/2022] Open
Abstract
Background: The gut microbiome (GMB) generates numerous small chemicals that can be absorbed by the host and variously biotransformed, incorporated, or excreted. The resulting metabolome can provide information about the state of the GMB, of the host, and of their relationship. Exploiting this information in the service of biomarker development is contingent on knowing the GMB-sensitivity of the individual chemicals comprising the metabolome. In this regard, human studies have lagged far behind animal studies. Accordingly, we tested the hypothesis that serum levels of chemicals unequivocally demonstrated to be GMB-sensitive in rodent models would also be affected in a clinical patient sample treated with broad spectrum antibiotics. Methods: We collected serum samples from 20 hospitalized patients before, during, and after treatment with broad-spectrum antibiotics. We also collected samples from 5 control patients admitted to the hospital but not prescribed antibiotics. We submitted the samples for a non-targeted metabolomic analysis and then focused on chemicals known to be affected both by germ-free status and by antibiotic treatment in the mouse and/or rat. Results: Putative identification was obtained for 499 chemicals in human serum. An aggregate analysis did not show any time x treatment interactions. However, our literature search identified 10 serum chemicals affected both by germ-free status and antibiotic treatment in the mouse or rat. Six of those chemicals were measured in our patient samples and additionally met criteria for inclusion in a focused analysis. Serum levels of 5 chemicals (p-cresol sulfate, phenol sulfate, hippurate, indole propionate, and indoxyl sulfate) declined significantly in our group of antibiotic-treated patients but did not change in our patient control group. Conclusions: Broad-spectrum antibiotic treatment in patients lowered serum levels of selected chemicals previously demonstrated to be GMB-sensitive in rodent models. Interestingly, all those chemicals are known to be uremic solutes that can be derived from aromatic amino acids (L-phenylalanine, L-tyrosine, or L-tryptophan) by anaerobic bacteria, particularly Clostridial species. We conclude that judiciously selected serum chemicals can reliably detect antibiotic-induced suppression of the GMB in man and thus facilitate further metabolome-based biomarker development.
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Affiliation(s)
- George E Jaskiw
- Psychiatry Service, Veterans Affairs Northeast Ohio Healthcare System (VANEOHS), Cleveland, Ohio.,School of Medicine, Case Western Reserve University, Cleveland, Ohio
| | - Mark E Obrenovich
- Pathology and Laboratory Medicine Service, VANEOHS, Cleveland, Ohio.,Research Service, VANEOHS, Cleveland, Ohio.,Department of Chemistry, Case Western Reserve University, Cleveland, Ohio
| | - Sirisha Kundrapu
- School of Medicine, Case Western Reserve University, Cleveland, Ohio
| | - Curtis J Donskey
- School of Medicine, Case Western Reserve University, Cleveland, Ohio.,Geriatric Research, Education and Clinical Center, VANEOHS, Cleveland, Ohio
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22
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Iqbal Y, Cottrell JJ, Suleria HA, Dunshea FR. Gut Microbiota-Polyphenol Interactions in Chicken: A Review. Animals (Basel) 2020; 10:E1391. [PMID: 32796556 PMCID: PMC7460082 DOI: 10.3390/ani10081391] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/03/2020] [Accepted: 08/09/2020] [Indexed: 02/07/2023] Open
Abstract
The gastrointestinal tract of the chicken harbors very complex and diverse microbial communities including both beneficial and harmful bacteria. However, a dynamic balance is generally maintained in such a way that beneficial bacteria predominate over harmful ones. Environmental factors can negatively affect this balance, resulting in harmful effects on the gut, declining health, and productivity. This means modulating changes in the chicken gut microbiota is an effective strategy to improve gut health and productivity. One strategy is using modified diets to favor the growth of beneficial bacteria and a key candidate are polyphenols, which have strong antioxidant potential and established health benefits. The gut microbiota-polyphenol interactions are of vital importance in their effects on the gut microbiota modulation because it affects not only the composition of gut bacteria but also improves bioavailability of polyphenols through generation of more bioactive metabolites enhancing their health effects on morphology and composition of the gut microbiota. The object of this review is to improve the understanding of polyphenol interactions with the gut microbiota and highlights their potential role in modulation of the gut microbiota of chicken.
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Affiliation(s)
- Yasir Iqbal
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia; (Y.I.); (J.J.C.); (H.A.R.S.)
| | - Jeremy J. Cottrell
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia; (Y.I.); (J.J.C.); (H.A.R.S.)
| | - Hafiz A.R. Suleria
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia; (Y.I.); (J.J.C.); (H.A.R.S.)
| | - Frank R. Dunshea
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia; (Y.I.); (J.J.C.); (H.A.R.S.)
- Faculty of Biological Sciences, The University of Leeds, Leeds LS2 9JT, UK
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23
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Seyed Hameed AS, Rawat PS, Meng X, Liu W. Biotransformation of dietary phytoestrogens by gut microbes: A review on bidirectional interaction between phytoestrogen metabolism and gut microbiota. Biotechnol Adv 2020; 43:107576. [PMID: 32531317 DOI: 10.1016/j.biotechadv.2020.107576] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 06/03/2020] [Accepted: 06/03/2020] [Indexed: 12/12/2022]
Abstract
Phytoestrogens are a class of plant produced polyphenolic compounds with diphenolic structure, which is similar to 17β-estradiol. These phytoestrogens preferentially bind to estrogen receptors, however, with weak affinity. Recently, many studies have found that these phytoestrogens can be transformed by gut microbiota through novel enzymatic reactions into metabolites with altered bioactivity. Recent studies have also implied that these metabolites could possibly modulate the host gut ecosystem, gene expression, metabolism and the immune system. Thus, isolating gut microbes capable of biotransforming phytoestrogens and characterizing the novel enzymatic reactions involved are principal to understand the mechanisms of beneficial effects brought by gut microbiota and their metabolism on phytoestrogens, and to provide the theoretical knowledge for the development of functional probiotics. In the present review, we summarized works on gut microbial biotransformation of phytoestrogens, including daidzin (isoflavone), phenylnaringenin (prenylflavonoid), lignans, resveratrol (stilbene) and ellagitannins. We mainly focus on gut bacterial isolation, metabolic pathway characterization, and the bidirectional interaction of phytoestrogens with gut microbes to illustrate the novel metabolic capability of gut microbiota and the methods used in these studies.
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Affiliation(s)
- Ahkam Saddam Seyed Hameed
- State Key Laboratory of Microbial Technology, Microbial Technology Institute, Shandong University, No.72 Binhai Road, Qingdao 266237, PR China
| | - Parkash Singh Rawat
- State Key Laboratory of Microbial Technology, Microbial Technology Institute, Shandong University, No.72 Binhai Road, Qingdao 266237, PR China
| | - Xiangfeng Meng
- State Key Laboratory of Microbial Technology, Microbial Technology Institute, Shandong University, No.72 Binhai Road, Qingdao 266237, PR China.
| | - Weifeng Liu
- State Key Laboratory of Microbial Technology, Microbial Technology Institute, Shandong University, No.72 Binhai Road, Qingdao 266237, PR China
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24
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Wu ZY, Sang LX, Chang B. Isoflavones and inflammatory bowel disease. World J Clin Cases 2020; 8:2081-2091. [PMID: 32548137 PMCID: PMC7281056 DOI: 10.12998/wjcc.v8.i11.2081] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 03/27/2020] [Accepted: 04/24/2020] [Indexed: 02/05/2023] Open
Abstract
Isoflavones constitute a class of plant hormones including genistein, daidzein, glycitein, formononetin, biochanin A, and irilone, and the major source of human intake is soybeans. Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease including ulcerative colitis, Crohn’s disease, and indeterminate colitis, which seriously affects the quality of life of patients and has become a global health problem. Although the pathogenesis of IBD is not very clear, many factors are thought to be related to the occurrence and development of IBD such as genes, immunity, and intestinal flora. How to control IBD effectively for a long time is still a problem for gastroenterologists. Diet has an important effect on IBD. Patients with IBD should pay more attention to diet. To date, many studies have reported that isoflavones have both good and bad effects on IBD. Isoflavones have many activities such as regulating the inflammatory signal pathways and affecting intestinal barrier functions and gut flora. They can also act through estrogen receptors, as they have a similar structure to estrogen. Isoflavones are easy to get from diet for human. Whether they are valuable to be applied to the treatment of IBD is worth studying. This review summarizes the relationship between isoflavones and IBD.
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Affiliation(s)
- Ze-Yu Wu
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Cortés-Martín A, Selma MV, Tomás-Barberán FA, González-Sarrías A, Espín JC. Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes. Mol Nutr Food Res 2020; 64:e1900952. [PMID: 32196920 DOI: 10.1002/mnfr.201900952] [Citation(s) in RCA: 177] [Impact Index Per Article: 35.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 02/19/2020] [Indexed: 12/23/2022]
Abstract
The full consensus on the role of dietary polyphenols as human-health-promoting compounds remains elusive. The two-way interaction between polyphenols and gut microbiota (GM) (i.e., modulation of GM by polyphenols and their catabolism by the GM) is determinant in polyphenols' effects. The identification of human metabotypes associated with a differential gut microbial metabolism of polyphenols has opened new research scenarios to explain the inter-individual variability upon polyphenols consumption. The metabotypes unequivocally identified so far are those involved in the metabolism of isoflavones (equol and(or) O-desmethylangolesin producers versus non-producers) and ellagic acid (urolithin metabotypes, including producers of only urolithin-A (UM-A), producers of urolithin-A, isourolithin-A, and urolithin-B (UM-B), and non-producers (UM-0)). In addition, the microbial metabolites (phenolic-derived postbiotics) such as equol, urolithins, valerolactones, enterolactone, and enterodiol, and 8-prenylnaringenin, among others, can exert differential health effects. The knowledge is updated and position is taken here on i) the two-way interaction between GM and polyphenols, ii) the evidence between phenolic-derived postbiotics and health, iii) the role of metabotypes as biomarkers of GM and the clustering of individuals depending on their metabotypes (metabotyping) to explain polyphenols' effects, and iv) the gut microbial metabolism of catecholamines to illustrate the intersection between personalized nutrition and precision medicine.
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Affiliation(s)
- Adrián Cortés-Martín
- Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Campus de Espinardo, Murcia, 30100, Spain
| | - María Victoria Selma
- Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Campus de Espinardo, Murcia, 30100, Spain
| | - Francisco Abraham Tomás-Barberán
- Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Campus de Espinardo, Murcia, 30100, Spain
| | - Antonio González-Sarrías
- Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Campus de Espinardo, Murcia, 30100, Spain
| | - Juan Carlos Espín
- Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Campus de Espinardo, Murcia, 30100, Spain
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Cady N, Peterson SR, Freedman SN, Mangalam AK. Beyond Metabolism: The Complex Interplay Between Dietary Phytoestrogens, Gut Bacteria, and Cells of Nervous and Immune Systems. Front Neurol 2020; 11:150. [PMID: 32231636 PMCID: PMC7083015 DOI: 10.3389/fneur.2020.00150] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 02/14/2020] [Indexed: 12/21/2022] Open
Abstract
The human body has a large, diverse community of microorganisms which not only coexist with us, but also perform many important physiological functions, including metabolism of dietary compounds that we are unable to process ourselves. Furthermore, these bacterial derived/induced metabolites have the potential to interact and influence not only the local gut environment, but the periphery via interaction with and modulation of cells of the immune and nervous system. This relationship is being further appreciated every day as the gut microbiome is researched as a potential target for immunomodulation. A common feature among inflammatory diseases including relapsing-remitting multiple sclerosis (RRMS) is the presence of gut microbiota dysbiosis when compared to healthy controls. However, the specifics of these microbiota-neuro-immune system interactions remain unclear. Among all factors, diet has emerged as a strongest factor regulating structure and function of gut microbial community. Phytoestrogens are one class of dietary compounds emerging as potentially being of interest in this interaction as numerous studies have identified depletion of phytoestrogen-metabolizing bacteria such as Adlercreutzia, Parabacteroides and Prevotella in RRMS patients. Additionally, phytoestrogens or their metabolites have been reported to show protective effects when compounds are administered in the animal model of MS, Experimental Autoimmune Encephalomyelitis (EAE). In this review, we will illustrate the link between MS and phytoestrogen metabolizing bacteria, characterize the importance of gut bacteria and their mechanisms of action in the production of phytoestrogen metabolites, and discuss what is known about the interactions of specific compounds with cells immune and nervous system. A better understanding of gut bacteria-mediated phytoestrogen metabolism and mechanisms through which these metabolites facilitate their biological actions will help in development of novel therapeutic options for MS as well as other inflammatory diseases.
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Affiliation(s)
- Nicole Cady
- Department of Pathology, University of Iowa, Iowa City, IA, United States
| | | | | | - Ashutosh K. Mangalam
- Department of Pathology, University of Iowa, Iowa City, IA, United States
- Immunology, University of Iowa, Iowa City, IA, United States
- Molecular Medicine, University of Iowa, Iowa City, IA, United States
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Montalesi E, Cipolletti M, Cracco P, Fiocchetti M, Marino M. Divergent Effects of Daidzein and its Metabolites on Estrogen-Induced Survival of Breast Cancer Cells. Cancers (Basel) 2020; 12:E167. [PMID: 31936631 PMCID: PMC7017042 DOI: 10.3390/cancers12010167] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 01/13/2023] Open
Abstract
Although soy consumption is associated with breast cancer prevention, the low bioavailability and the extensive metabolism of soy-active components limit their clinical application. Here, the impact of daidzein (D) and its metabolites on estrogen-dependent anti-apoptotic pathway has been evaluated in breast cancer cells. In estrogen receptor α-positive breast cancer cells treated with D and its metabolites, single or in mixture, ERα activation and Neuroglobin (NGB) levels, an anti-apoptotic estrogen/ERα-inducible protein, were evaluated. Moreover, the apoptotic cascade activation, as well as the cell number after stimulation was assessed in the absence/presence of paclitaxel to determine the compound effects on cell susceptibility to a chemotherapeutic agent. Among the metabolites, only D-4'-sulfate maintains the anti-estrogenic effect of D, reducing the NGB levels and rendering breast cancer cells more prone to the paclitaxel treatment, whereas other metabolites showed estrogen mimetic effects, or even estrogen independent effects. Intriguingly, the co-stimulation of D and gut metabolites strongly reduced D effects. The results highlight the important and complex influence of metabolic transformation on isoflavones physiological effects and demonstrate the need to take biotransformation into account when assessing the potential health benefits of consumption of soy isoflavones in cancer.
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Affiliation(s)
| | | | | | | | - Maria Marino
- Department of Science, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Italy; (E.M.); (M.C.); (P.C.); (M.F.)
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Peirotén Á, Bravo D, Landete JM. Bacterial metabolism as responsible of beneficial effects of phytoestrogens on human health. Crit Rev Food Sci Nutr 2019; 60:1922-1937. [PMID: 31161778 DOI: 10.1080/10408398.2019.1622505] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Phytoestrogens (PE) are compounds found in plants such as soy (isoflavones), flax seeds and cereals (lignans) and pomegranates (ellagitannins). PE have shown estrogenic/antiestrogenic, antioxidant, anti-inflammatory, antineoplastic and apoptotic activities. The human studies are showing promising although inconsistent results about the beneficial effects of PE on ameliorating the menopausal symptoms or reducing the risk of certain cancers, cardiovascular disease or diabetes. The effects of PE on the organism are mediated by the intestinal microbiota, which transforms them into bioactive PE such as genistein, equol, enterolignans and certain urolithins. In this work, we review the most recent findings about the bacteria able to metabolize PE, together with the latest studies on the effects of PE on health. In addition, we describe the possible factors hindering the demonstration of the beneficial effect of PE on health, evincing the importance of measuring the actual circulating PE in order to encompass the variability of PE metabolism due to the intestinal microbiota. With this in mind, we also explore an approach to ensure the access to bioactive PE.
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Affiliation(s)
- Ángela Peirotén
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain
| | - Daniel Bravo
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain
| | - José M Landete
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain
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Deorukhkar A, Ananthanarayan L. Consumption of Decorticated Pulses Ensures the Optimum Intake of Isoflavones by the Urban Indian Population. Nutr Cancer 2019; 71:870-880. [PMID: 30686044 DOI: 10.1080/01635581.2018.1559936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Sample urban population was assessed for consumption of legumes. Genistein and daidzein content of commonly consumed legumes was evaluated to estimate the isoflavone intake through the consumption of these legumes by selected population. Total genistein content of all legumes considered for analysis was found to be in the range of 0.60 to 8.65 mg per 100 g whereas total daidzein content was found to be in the range of 1.10 to 30.37 mg per 100 g in selected legumes. Chickpea, kabuli, whole (Cicer arietinum), pigeon pea, split, decorticated (Cajanus cajan), chickpea, split, decorticated (Cicer arietinum) showed a high amount of genistein and daidzein among selected legumes. Average isoflavone consumption by selected population was found to be 18.22 mg/d through the consumption of legumes. Consumption of pigeon pea (split, decorticated) and chickpea (split, decorticated) was found to be highest at 371.6 g/month and 329.7 g/month, and hence were found to contribute 18% and 14% to total isoflavone intake, respectively. The comparatively high content of isoflavones and inclusion as a staple in the diet have resulted in making the split, decorticated pulses (chickpea, pigeon pea, lentil, green gram, black gram) a chief isoflavone source for selected population irrespective of their demographic differences.
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Affiliation(s)
- Anuradha Deorukhkar
- a Food Engineering and Technology Department , Institute of Chemical Technology , Mumbai , India
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Lee PG, Lee UJ, Song H, Choi KY, Kim BG. Recent advances in the microbial hydroxylation and reduction of soy isoflavones. FEMS Microbiol Lett 2018; 365:5089968. [PMID: 30184116 DOI: 10.1093/femsle/fny195] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 08/31/2018] [Indexed: 12/17/2023] Open
Abstract
Soy isoflavones are naturally occurring phytochemicals, which are biotransformed into functional derivatives through oxidative and reductive metabolic pathways of diverse microorganisms. Such representative derivatives, ortho-dihydroxyisoflavones (ODIs) and equols, have attracted great attention for their versatile health benefits since they were found from soybean fermented foods and human intestinal fluids. Recently, scientists in food technology, nutrition and microbiology began to understand their correct biosynthetic pathways and nutraceutical values, and have attempted to produce the valuable bioactive compounds using microbial fermentation and whole-cell/enzyme-based biotransformation. Furthermore, artificial design of microbial catalysts and/or protein engineering of oxidoreductases were also conducted to enhance production efficiency and regioselectivity of products. This minireview summarizes and introduces the past year's studies and recent advances in notable production of ODIs and equols, and provides information on available microbial species and their catalytic performance with perspectives on industrial application.
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Affiliation(s)
- Pyung-Gang Lee
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
- Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea
| | - Uk-Jae Lee
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
- Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea
| | - Hanbit Song
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
- Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea
| | - Kwon-Young Choi
- Department of Environmental Engineering, College of Engineering, Ajou University, Suwon 16499, Republic of Korea
| | - Byung-Gee Kim
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
- Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea
- Bioengineering Institute, Seoul National University, Seoul 08826, South Korea
- Institute of Bioengineering Research, Seoul National University, Seoul 08826, Republic of Korea
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Das D, Sarkar S, Bordoloi J, Wann SB, Kalita J, Manna P. Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes. Biofactors 2018; 44:407-417. [PMID: 30191623 DOI: 10.1002/biof.1439] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 06/20/2018] [Indexed: 12/30/2022]
Abstract
Over the last decades, the incidence of type 2 diabetes (T2D) is increasing substantially. Emerging evidences from epidemiological studies have shown the association between higher intake of soy isoflavones and reduced risk of T2D and its associated health risks. Daidzein, a soy isoflavone, has been found to have a promising therapeutic potential in managing T2D pathophysiology. Fermented soybean is the major source of daidzein; however, it can also be formed via the consumption of its glycosylated moiety, daidzin with subsequent hydrolysis by intestinal bacterial enzyme. Many studies reported the prophylactic effect of daidzein on the improvement of hyperglycemia, insulin resistance, dislipidemia, obesity, inflammation, and other complications associated with T2D. The molecular mechanisms underlying the action of daidzein include diverged pathways where daidzein has been shown to interact with several signaling molecules and receptors to achieve desirable effect. Although the specific molecular mechanism is still elusive, further studies are thus needed to understand it in detail. In this review, we discuss the antidiabetic potential of daidzein with respect to the evidences from various clinical, preclinical, and cell culture studies and the underlying molecular mechanism in a precise way to have a comprehensive account on this isoflavone with promising therapeutic potential. © 2018 BioFactors, 44(5):407-417, 2018.
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Affiliation(s)
- Dibyendu Das
- Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
- Academy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, India
| | - Sanjib Sarkar
- Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
- Academy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, India
| | - Jijnasa Bordoloi
- Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
- Academy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, India
| | - Sawlang Borsingh Wann
- Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
- Academy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, India
| | - Jatin Kalita
- Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
- Academy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, India
| | - Prasenjit Manna
- Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
- Academy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam, India
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Murota K, Nakamura Y, Uehara M. Flavonoid metabolism: the interaction of metabolites and gut microbiota. Biosci Biotechnol Biochem 2018; 82:600-610. [DOI: 10.1080/09168451.2018.1444467] [Citation(s) in RCA: 311] [Impact Index Per Article: 44.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Abstract
Several dietary flavonoids exhibit anti-oxidative, anti-inflammatory, and anti-osteoporotic activities relevant to prevention of chronic diseases, including lifestyle-related diseases. Dietary flavonoids (glycoside forms) are enzymatically hydrolyzed and absorbed in the intestine, and are conjugated to their glucuronide/sulfate forms by phase II enzymes in epithelial cells and the liver. The intestinal microbiota plays an important role in the metabolism of flavonoids found in foods. Some specific products of bacterial transformation, such as ring-fission products and reduced metabolites, exhibit enhanced properties. Studies on the metabolism of flavonoids by the intestinal microbiota are crucial for understanding the role of these compounds and their impact on our health. This review focused on the metabolic pathways, bioavailability, and physiological role of flavonoids, especially metabolites of quercetin and isoflavone produced by the intestinal microbiota.
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Affiliation(s)
- Kaeko Murota
- Faculty of Science and Technology, Department of Life Science, Kindai University, Osaka, Japan
| | - Yoshimasa Nakamura
- Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan
| | - Mariko Uehara
- Faculty of Applied Bioscience, Department of Nutritional Science and Food Safety, Tokyo University of Agriculture, Tokyo, Japan
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Trnková A, Šancová K, Zapletalová M, Kašparovská J, Dadáková K, Křížová L, Lochman J, Hadrová S, Ihnatová I, Kašparovský T. Determination of in vitro isoflavone degradation in rumen fluid. J Dairy Sci 2018; 101:5134-5144. [PMID: 29550126 DOI: 10.3168/jds.2017-13610] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 01/26/2018] [Indexed: 11/19/2022]
Abstract
The aim of this study was to determine the degradation of dietary isoflavones in rumen fluid under 2 feeding regimens. The experiments were performed in vitro using a rumen fluid buffer system. The rumen fluid was taken from cows fed either a hay diet or a concentrate-rich diet (the diet consisted of 34.6% maize silage, 17.6% haylage, 12.8% alfalfa hay, and 35.0% supplemental mixture on a dry matter basis). As a source of isoflavones, 40% soybean extract (Biomedica, Prague, Czech Republic) at levels of 5, 25, 50, and 75 mg per 40 mL of rumen fluid was used. Samples of soybean extract were incubated in triplicate at 39°C for 0, 3.0, 6.0, 12.0, and 24.0 h in incubation solution. The metabolism of daidzein and genistein was faster under concentrate-rich diet conditions. In general, production of equol started after 3 to 6 h of incubation and reached the highest rate after approximately 12 h of incubation regardless of the type of diet or concentration of extract. In most of the experiments, production of equol continued after 24 h of incubation. Generally, equol production was greater under the hay diet conditions. Furthermore, experiments with higher amounts of added soybean extract revealed possible inhibitory effects of high levels of isoflavones on the rumen microflora.
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Affiliation(s)
- Andrea Trnková
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Kateřina Šancová
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Martina Zapletalová
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Jitka Kašparovská
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Kateřina Dadáková
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Ludmila Křížová
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Jan Lochman
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Sylvie Hadrová
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Ivana Ihnatová
- Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic
| | - Tomáš Kašparovský
- Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic.
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Gaya P, Peirotén Á, Álvarez I, Medina M, Landete JM. Production of the bioactive isoflavone O-desmethylangolensin by Enterococcus faecium INIA P553 with high efficiency. J Funct Foods 2018. [DOI: 10.1016/j.jff.2017.11.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Genistein: Its role in metabolic diseases and cancer. Crit Rev Oncol Hematol 2017; 119:13-22. [PMID: 29065980 DOI: 10.1016/j.critrevonc.2017.09.004] [Citation(s) in RCA: 181] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 08/23/2017] [Accepted: 09/11/2017] [Indexed: 12/12/2022] Open
Abstract
Genistein is an isoflavone present in soy and is known to have multiple molecular effects, such as the inhibition of inflammation, promotion of apoptosis, and modulation of steroidal hormone receptors and metabolic pathways. Since these molecular effects impact carcinogenesis, cancer propagation, obesity, osteoporosis, and metabolic syndromes, genistein plays an important role in preventing and treating common disorders. The role of genistein has not been adequately evaluated in all these clinical settings. This review summarizes some of the known molecular effects of genistein and its potential role in health maintenance and treatment.
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Being overweight or obese is associated with harboring a gut microbial community not capable of metabolizing the soy isoflavone daidzein to O-desmethylangolensin in peri- and post-menopausal women. Maturitas 2017; 99:37-42. [PMID: 28364866 DOI: 10.1016/j.maturitas.2017.02.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 01/18/2017] [Accepted: 02/06/2017] [Indexed: 01/15/2023]
Abstract
OBJECTIVE Obesity can be a considerable health concern for peri- and post-menopausal women. Evidence suggests an association between the gut microbiome and obesity. The study objective was to evaluate the association between being overweight or obese and phenotypic markers of having an overall gut microbial environment not capable of metabolizing the isoflavone daidzein to equol or O-desmethylangolensin (ODMA). STUDY DESIGN Cross-sectional study of 137 peri- and 218 post-menopausal women, aged 44-55 years, who consumed at least three servings per week of soy (source of daidzein). Equol and ODMA producers and non-producers were identified based on urinary concentrations of daidzein, equol and ODMA in a 24-h urine sample. MAIN OUTCOME MEASURES Mean body mass index (BMI) and odds of obesity. RESULTS Fifty-one women were ODMA non-producers and 226 were equol non-producers. The ODMA non-producer phenotype was positively associated with obesity (OR: 3.33, 95% CI: 1.53, 7.23), and mean BMI was significantly higher in non-producers (28.9kg/m2) than in producers (26.7kg/m2), after adjusting for age, ethnicity, and menopausal status. Positive associations with being obese were observed in both peri-menopausal (OR=3.92, 95% CI: 0.90, 17.0) and post-menopausal (OR=3.00, 95% CI: 1.22, 7.70) women. The equol non-producer phenotype was not associated with obesity (OR=1.13, 95% CI: 0.64, 1.98), and mean BMI was not significantly different between equol producers (27.3kg/m2) and non-producers (26.5kg/m2). CONCLUSIONS These results suggest that the ODMA non-producer phenotype is associated with obesity in peri- and post-menopausal women. Further work is needed to confirm these observations in additional populations and to evaluate possible mechanisms.
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Xu J, Chen HB, Li SL. Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota. Med Res Rev 2017; 37:1140-1185. [PMID: 28052344 DOI: 10.1002/med.21431] [Citation(s) in RCA: 243] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2016] [Revised: 10/21/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023]
Abstract
Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs. More advanced experimental designs are recommended for future study, such as overall chemical characterization of gut microbiota-metabolized HMs, direct microbial analysis of HM-targeted gut microbiota, and precise gut microbiota research model development. The outcomes of such research can further elucidate the interactions between HMs and gut microbiota, thereby opening a new window for defining the scientific basis of HMs and for guiding HM-based drug discovery.
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Affiliation(s)
- Jun Xu
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Hu-Biao Chen
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Song-Lin Li
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, P.R. China.,Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, 210028, P.R. China
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Frankenfeld CL. Cardiometabolic risk and gut microbial phytoestrogen metabolite phenotypes. Mol Nutr Food Res 2016; 61. [DOI: 10.1002/mnfr.201500900] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 06/18/2016] [Accepted: 07/14/2016] [Indexed: 12/18/2022]
Affiliation(s)
- Cara L. Frankenfeld
- Department of Global and Community Health; George Mason University; Fairfax VA USA
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Landete JM, Arqués J, Medina M, Gaya P, de Las Rivas B, Muñoz R. Bioactivation of Phytoestrogens: Intestinal Bacteria and Health. Crit Rev Food Sci Nutr 2016; 56:1826-43. [PMID: 25848676 DOI: 10.1080/10408398.2013.789823] [Citation(s) in RCA: 143] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Phytoestrogens are polyphenols similar to human estrogens found in plants or derived from plant precursors. Phytoestrogens are found in high concentration in soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc. They comprise several classes of chemical compounds (stilbenes, coumestans, isoflavones, ellagitannins, and lignans) which are structurally similar to endogenous estrogens but which can have both estrogenic and antiestrogenic effects. Although epidemiological and experimental evidence indicates that intake of phytoestrogens in foods may be protective against certain chronic diseases, discrepancies have been observed between in vivo and in vitro experiments. The microbial transformations have not been reported so far in stilbenes and coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by intestinal bacteria to produce equol, urolithins, and enterolignans, respectively. Equol, urolithin, and enterolignans are more bioavailable, and have more estrogenic/antiestrogenic and antioxidant activity than their precursors. Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and induce antiproliferative and apoptosis-inducing activities. The transformation of isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to be protective against certain chronic diseases, as cancer, cardiovascular disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and health effects of dietary phytoestrogens are strongly determined by the intestinal bacteria of each individual.
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Affiliation(s)
- J M Landete
- a Departamento de Tecnología de Alimentos , Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) . Madrid , Spain
| | - J Arqués
- a Departamento de Tecnología de Alimentos , Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) . Madrid , Spain
| | - M Medina
- a Departamento de Tecnología de Alimentos , Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) . Madrid , Spain
| | - P Gaya
- a Departamento de Tecnología de Alimentos , Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) . Madrid , Spain
| | - B de Las Rivas
- b Departamento de Biotecnología Bacteriana , Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC) , Madrid , Spain
| | - R Muñoz
- b Departamento de Biotecnología Bacteriana , Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC) , Madrid , Spain
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Stevens JF, Maier CS. The Chemistry of Gut Microbial Metabolism of Polyphenols. PHYTOCHEMISTRY REVIEWS : PROCEEDINGS OF THE PHYTOCHEMICAL SOCIETY OF EUROPE 2016; 15:425-444. [PMID: 27274718 PMCID: PMC4888912 DOI: 10.1007/s11101-016-9459-z] [Citation(s) in RCA: 154] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Accepted: 03/02/2016] [Indexed: 05/18/2023]
Abstract
Gut microbiota contribute to the metabolism of dietary polyphenols and affect the bioavailability of both the parent polyphenols and their metabolites. Although there is a large number of reports of specific polyphenol metabolites, relatively little is known regarding the chemistry and enzymology of the metabolic pathways utilized by specific microbial species and taxa, which is the focus of this review. Major classes of dietary polyphenols include monomeric and oligomeric catechins (proanthocyanidins), flavonols, flavanones, ellagitannins, and isoflavones. Gut microbial metabolism of representatives of these polyphenol classes can be classified as A- and C-ring cleavage (retro Claisen reactions), C-ring cleavage mediated by dioxygenases, dehydroxylations (decarboxylation or reduction reactions followed by release of H2O molecules), and hydrogenations of alkene moieties in polyphenols, such as resveratrol, curcumin, and isoflavones (mediated by NADPH-dependent reductases). The qualitative and quantitative metabolic output of the gut microbiota depends to a large extent on the metabolic capacity of individual taxa, which emphasizes the need for assessment of functional analysis in conjunction with determinations of gut microbiota compositions.
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Affiliation(s)
- Jan F Stevens
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon 97330; Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97330
| | - Claudia S Maier
- Department of Chemistry, Oregon State University, Corvallis, Oregon 97330; Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97330
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Kasparovska J, Pecinkova M, Dadakova K, Krizova L, Hadrova S, Lexa M, Lochman J, Kasparovsky T. Effects of Isoflavone-Enriched Feed on the Rumen Microbiota in Dairy Cows. PLoS One 2016; 11:e0154642. [PMID: 27124615 PMCID: PMC4849651 DOI: 10.1371/journal.pone.0154642] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 04/15/2016] [Indexed: 01/04/2023] Open
Abstract
In this study, we compared the effects of two diets containing different isoflavone concentrations on the isoflavone transfer from feed into milk and on the rumen microbiota in lactating dairy cows. The on-farm experiment was conducted on twelve lactating Czech Fleckvieh x Holstein cows divided into two groups, each with similar mean milk yield. Twice daily, cows were individually fed a diet based on maize silage, meadow hay and supplemental mixture. Control group (CTRL) received the basal diet while the experimental group (EXP) received the basal diet supplemented with 40% soybean isoflavone extract. The average daily isoflavone intake in the EXP group (16 g/day) was twice as high as that in the CTRL group (8.4 g/day, P<0.001). Total isoflavone concentrations in milk from the CTRL and EXP groups were 96.89 and 276.07 μg/L, respectively (P<0.001). Equol concentrations in milk increased from 77.78 μg/L in the CTRL group to 186.30 μg/L in the EXP group (P<0.001). The V3-4 region of bacterial 16S rRNA genes was used for metagenomic analysis of the rumen microbiome. The experimental cows exhibited fewer OTUs at a distance level of 0.03 compared to control cows (P<0.05) and reduced microbial richness compared to control cows based on the calculated Inverse Simpson and Shannon indices. Non-metric multidimensional scaling analysis showed that the major contributor to separation between the experimental and control groups were changes in the representation of bacteria belonging to the phyla Bacteroidetes, Proteobacteria, Firmicutes, and Planctomycetes. Surprisingly, a statistically significant positive correlation was found only between isoflavones and the phyla Burkholderiales (r = 0.65, P<0.05) and unclassified Betaproteobacteria (r = 0.58, P<0.05). Previous mouse and human studies of isoflavone effects on the composition of gastrointestinal microbial populations generally report similar findings.
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Affiliation(s)
- Jitka Kasparovska
- Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Martina Pecinkova
- Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Katerina Dadakova
- Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Ludmila Krizova
- Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Sylvie Hadrova
- Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Matej Lexa
- Department of Information Technologies, Faculty of Informatics, Masaryk University, Brno, Czech Republic
| | - Jan Lochman
- Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Tomas Kasparovsky
- Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
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Lorent K, Gong W, Koo KA, Waisbourd-Zinman O, Karjoo S, Zhao X, Sealy I, Kettleborough RN, Stemple DL, Windsor PA, Whittaker SJ, Porter JR, Wells RG, Pack M. Identification of a plant isoflavonoid that causes biliary atresia. Sci Transl Med 2016; 7:286ra67. [PMID: 25947162 DOI: 10.1126/scitranslmed.aaa1652] [Citation(s) in RCA: 105] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Biliary atresia (BA) is a rapidly progressive and destructive fibrotic disorder of unknown etiology affecting the extrahepatic biliary tree of neonates. Epidemiological studies suggest that an environmental factor, such as a virus or toxin, is the cause of the disease, although none have been definitively established. Several naturally occurring outbreaks of BA in Australian livestock have been associated with the ingestion of unusual plants by pregnant animals during drought conditions. We used a biliary secretion assay in zebrafish to isolate a previously undescribed isoflavonoid, biliatresone, from Dysphania species implicated in a recent BA outbreak. This compound caused selective destruction of the extrahepatic, but not intrahepatic, biliary system of larval zebrafish. A mutation that enhanced biliatresone toxicity mapped to a region of the zebrafish genome that has conserved synteny with an established human BA susceptibility locus. The toxin also caused loss of cilia in neonatal mouse extrahepatic cholangiocytes in culture and disrupted cell polarity and monolayer integrity in cholangiocyte spheroids. Together, these findings provide direct evidence that BA could be initiated by perinatal exposure to an environmental toxin.
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Affiliation(s)
- Kristin Lorent
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Weilong Gong
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Kyung A Koo
- Department of Biological Sciences, University of the Sciences, Philadelphia, PA 19104, USA
| | - Orith Waisbourd-Zinman
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Sara Karjoo
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Xiao Zhao
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Ian Sealy
- Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
| | - Ross N Kettleborough
- Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
| | - Derek L Stemple
- Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
| | - Peter A Windsor
- Faculty of Veterinary Science, University of Sydney, Camden, New South Wales 2570, Australia
| | - Stephen J Whittaker
- Hume Livestock Health and Pest Authority, Albury, New South Wales 2640, Australia
| | - John R Porter
- Department of Biological Sciences, University of the Sciences, Philadelphia, PA 19104, USA
| | - Rebecca G Wells
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
| | - Michael Pack
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Niwa T, Yokoyama SI, Matsugasaki N, Inomata E, Taira A, Osawa T. Stereochemical determination of O-desmethylangolensin produced from daidzein. Food Chem 2015; 171:153-6. [PMID: 25308655 DOI: 10.1016/j.foodchem.2014.08.122] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2014] [Revised: 07/25/2014] [Accepted: 08/27/2014] [Indexed: 11/18/2022]
Abstract
We had isolated an O-desmethylangolensin (O-DMA)-producing bacterium, Clostridium rRNA cluster XIVa strain SY8519. According to chiral separation using HPLC, the SY8519-produced O-DMA exhibited high optical purity. To determine the absolute stereochemistry of O-DMA, we prepared 2-(4-hydroxyphenyl)propionic acid (2-HPPA) from the O-DMA using the Baeyer-Villiger reaction. From chiral analysis of the product, the major peak had the same stereochemistry to that of 2-HPPA produced from genistein by the same bacteria. As we have determined the stereochemistry of SY8519-produced 2-HPPA to have an R configuration, by the chemical synthesis of (S)-2-HPPA, the SY8519-produced O-DMA must also possess R stereochemistry at the 2-position. To study the stereoselective metabolism, we applied racemic dihydrodaidzein to SY8519. The O-DMA was isolated from the culture media and starting material was also recovered. The O-DMA produced was optically active in a similar manner to that produced from daidzein. However, the remaining dihydrodaidzein exhibited no difference between the enantiomers. These results suggested that SY8519 produces (R)-O-DMA from both enantiomers of dihydrodaidzein.
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Affiliation(s)
- Toshio Niwa
- Department of Human Health and Nutrition, Shokei Gakuin University, 4-10-1, Yurigaoka, Natori, Miyagi 981-1295, Japan.
| | - Shin-ichiro Yokoyama
- Department of Food Technology, Industrial Technology Center, Gifu Prefectural Government, 47 Kitaoyobi, Kasamatsu-cho, Hashima-gun, Gifu 501-6064, Japan
| | - Natsuki Matsugasaki
- Department of Human Health and Nutrition, Shokei Gakuin University, 4-10-1, Yurigaoka, Natori, Miyagi 981-1295, Japan
| | - Eri Inomata
- Department of Human Health and Nutrition, Shokei Gakuin University, 4-10-1, Yurigaoka, Natori, Miyagi 981-1295, Japan
| | - Asako Taira
- Department of Human Health and Nutrition, Shokei Gakuin University, 4-10-1, Yurigaoka, Natori, Miyagi 981-1295, Japan
| | - Toshihiko Osawa
- Department of Health and Nutrition, Faculty of Psychological & Physical Science, Aichi Gakuin University, 12, Araike, Iwasaki-cho, Nisshin, Aichi 470-0195, Japan
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Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. BIOMED RESEARCH INTERNATIONAL 2015; 2015:905215. [PMID: 25802870 PMCID: PMC4352739 DOI: 10.1155/2015/905215] [Citation(s) in RCA: 495] [Impact Index Per Article: 49.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 10/13/2014] [Accepted: 10/19/2014] [Indexed: 02/07/2023]
Abstract
Polyphenolic compounds are plant nutraceuticals showing a huge structural diversity, including chlorogenic acids, hydrolyzable tannins, and flavonoids (flavonols, flavanones, flavan-3-ols, anthocyanidins, isoflavones, and flavones). Most of them occur as glycosylated derivatives in plants and foods. In order to become bioactive at human body, these polyphenols must undergo diverse intestinal transformations, due to the action of digestive enzymes, but also by the action of microbiota metabolism. After elimination of sugar tailoring (generating the corresponding aglycons) and diverse hydroxyl moieties, as well as further backbone reorganizations, the final absorbed compounds enter the portal vein circulation towards liver (where other enzymatic transformations take place) and from there to other organs, including behind the digestive tract or via blood towards urine excretion. During this transit along diverse tissues and organs, they are able to carry out strong antiviral, antibacterial, and antiparasitic activities. This paper revises and discusses these antimicrobial activities of dietary polyphenols and their relevance for human health, shedding light on the importance of polyphenols structure recognition by specific enzymes produced by intestinal microbial taxa.
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Li M, Li H, Zhang C, Wang XL, Chen BH, Hao QH, Wang SY. Enhanced biosynthesis of O-desmethylangolensin from daidzein by a novel oxygen-tolerant cock intestinal bacterium in the presence of atmospheric oxygen. J Appl Microbiol 2015; 118:619-28. [PMID: 25523278 DOI: 10.1111/jam.12732] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 11/19/2014] [Accepted: 12/15/2014] [Indexed: 11/27/2022]
Abstract
AIMS To improve the oxygen-tolerant capability of a newly isolated anaerobic bacterium and to biosynthesize O-desmethylangolensin (O-Dma) from daidzein aerobically. METHODS AND RESULTS After a long-term domestication process, an oxygen-tolerant bacterium, which we named Aeroto-AUH-JLC108, was derived from the newly isolated obligate anaerobic bacterium Clostridium sp. AUH-JLC108. Strain Aeroto-AUH-JLC108 differed from the natively anaerobic wild-type strain AUH-JLC108 by various characteristics, including a change in bacterial shape, biochemical characteristics and 16S rRNA gene sequences. Both the growth speed and the maximal optical density (OD) value of strain Aeroto-AUH-JLC108 grown aerobically were significantly increased compared to that of the wild-type strain grown anaerobically. The maximal concentration of the substrate daidzein that the oxygen-tolerant strain Aeroto-AUH-JLC108 grown aerobically was able to convert efficiently was 2.0 mmol l(-1) and 0.6 mmol l(-1) for strain AUH-JLC108 that was grown anaerobically. CONCLUSIONS Strain Aeroto-AUH-JLC108 is a conditional oxygen-tolerant bacterium. The growth speed, bacterial growth mass and bioconversion capability of strain Aeroto-AUH-JLC108 grown aerobically was significantly increased compared to that of the wild-type strain AUH-JLC108 grown anaerobically. SIGNIFICANCE AND IMPACT OF THE STUDY Strain Aeroto-AUH-JLC108 is the first reported pure culture responsible for the formation of O-Dma from daidzein in the presence of atmospheric oxygen.
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Affiliation(s)
- M Li
- College of Life Sciences, Agricultural University of Hebei, Baoding, China
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The role of colonic bacteria in the metabolism of the natural isoflavone daidzin to equol. Metabolites 2015; 5:56-73. [PMID: 25594250 PMCID: PMC4381290 DOI: 10.3390/metabo5010056] [Citation(s) in RCA: 144] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Accepted: 01/07/2015] [Indexed: 12/18/2022] Open
Abstract
Isoflavones are found in leguminous plants, especially soybeans. They have a structural similarity to natural estrogens, which enables them to bind to estrogen receptors and elicit biological activities similar to natural estrogens. They have been suggested to be beneficial for the prevention and therapy of hormone-dependent diseases. After soy products are consumed, the bacteria of the intestinal microflora metabolize isoflavones to metabolites with altered absorption, bioavailability, and estrogenic characteristics. Variations in the effect of soy products have been correlated with the isoflavone metabolites found in plasma and urine samples of the individuals consuming soy products. The beneficial effects of the soy isoflavone daidzin, the glycoside of daidzein, have been reported in individuals producing equol, a reduction product of daidzein produced by specific colonic bacteria in individuals called equol producers. These individuals comprise 30% and 60% of populations consuming Western and soy-rich Asian diets, respectively. Since the higher percentage of equol producers in populations consuming soy-rich diets is correlated with a lower incidence of hormone-dependent diseases, considerable efforts have been made to detect the specific colonic bacteria involved in the metabolism of daidzein to the more estrogenic compound, equol, which should facilitate the investigation of the metabolic activities related to this compound.
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Hartono K, Reed S, Ankrah NA, Glahn RP, Tako E. Alterations in gut microflora populations and brush border functionality following intra-amniotic daidzein administration. RSC Adv 2015. [DOI: 10.1039/c4ra10962g] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Daidzein is an isoflavone found primarily in soybean and various soy-based products such as tofu.
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Affiliation(s)
- Karen Hartono
- USDA-ARS Robert Holley Center for Agriculture & Health
- Ithaca
- USA
- Division of Nutritional Sciences
- Cornell University
| | - Spenser Reed
- USDA-ARS Robert Holley Center for Agriculture & Health
- Ithaca
- USA
- Division of Nutritional Sciences
- Cornell University
| | | | | | - Elad Tako
- USDA-ARS Robert Holley Center for Agriculture & Health
- Ithaca
- USA
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Kim M, Han J. Absolute Configuration of (-)-2-(4-Hydroxyphenyl)propionic acid: Stereochemistry of Soy Isoflavone Metabolism. B KOREAN CHEM SOC 2014. [DOI: 10.5012/bkcs.2014.35.6.1883] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Isolation of 2,4,4′-Trihydroxydeoxybenzoin and 3′-Hydroxydaidzein from Soybean Miso. Biosci Biotechnol Biochem 2014; 74:1293-4. [DOI: 10.1271/bbb.100073] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Biotransformation of Daidzein to Equol by Crude Enzyme fromAsaccharobacter celatusAHU1763 Required an Anaerobic Environment. Biosci Biotechnol Biochem 2014; 73:1435-8. [DOI: 10.1271/bbb.80908] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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