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García CJ, Beltrán D, Frutos-Lisón MD, García-Conesa MT, Tomás-Barberán FA, García-Villalba R. New findings in the metabolism of the saffron apocarotenoids, crocins and crocetin, by the human gut microbiota. Food Funct 2024; 15:9315-9329. [PMID: 39171480 DOI: 10.1039/d4fo02233e] [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: 08/23/2024]
Abstract
The main constituents of saffron are the apocarotenoids crocins and crocetin, present in the stigmas. Numerous healthy properties, especially those related to the effects on the central nervous system, have been attributed to these compounds but the metabolites responsible for these effects are still unknown. Previous evidences in animal models suggest a role for the gut microbiota in the pharmacokinetics and the neuroprotective effects of these compounds. However, the interaction between these apocarotenoids and the gut microbiota has been poorly studied. In this article, we have thoroughly investigated the batch fermentation of crocin-1 and crocetin (10 μM) with human fecal samples of two donors at different incubation times (0-240 h) using a metabolomic approach. We corroborated a rapid transformation of crocin-1 which looses the glucose molecules through de-glycosylation reactions until its complete transformation into crocetin in 6 hours. A group of intermediate crocins with different degrees of glycosylation were detected in a very short time. Crocetin was further metabolized and new microbial metabolites produced by double-bond reduction and demethylation reactions were identified for the first time: dihydro and tetrahydro crocetins and di-demethyl crocetin. In addition, we detected changes in the levels of the short chain fatty acids valeric acid and hexanoic acid suggesting further structural modifications of crocetin or changes in the catabolic production of these compounds. This research is a pioneering study of the action of the human gut microbiota on the saffron apocarotenoids and goes one step further towards the discovery of metabolites potentially involved in the benefits of saffron.
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Affiliation(s)
- Carlos Javier García
- Research Group on Quality, Safety and Bioactivity of Plant-Derived Foods, CEBAS-CSIC, 30100 Murcia, Spain.
| | - David Beltrán
- Research Group on Quality, Safety and Bioactivity of Plant-Derived Foods, CEBAS-CSIC, 30100 Murcia, Spain.
| | - Maria Dolores Frutos-Lisón
- Research Group on Quality, Safety and Bioactivity of Plant-Derived Foods, CEBAS-CSIC, 30100 Murcia, Spain.
| | - Maria Teresa García-Conesa
- Research Group on Quality, Safety and Bioactivity of Plant-Derived Foods, CEBAS-CSIC, 30100 Murcia, Spain.
| | - Francisco A Tomás-Barberán
- Research Group on Quality, Safety and Bioactivity of Plant-Derived Foods, CEBAS-CSIC, 30100 Murcia, Spain.
| | - Rocío García-Villalba
- Research Group on Quality, Safety and Bioactivity of Plant-Derived Foods, CEBAS-CSIC, 30100 Murcia, Spain.
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Matsumoto W, Takemura M, Nanaura H, Ami Y, Maoka T, Shindo K, Kurihara S, Misawa N. Carotenoid productivity in human intestinal bacteria Eubacterium limosum and Leuconostoc mesenteroides with functional analysis of their carotenoid biosynthesis genes. ENGINEERING MICROBIOLOGY 2024; 4:100147. [PMID: 39629323 PMCID: PMC11611032 DOI: 10.1016/j.engmic.2024.100147] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 03/03/2024] [Accepted: 03/03/2024] [Indexed: 12/07/2024]
Abstract
The human intestinal microbiota that comprise over 1,000 species thrive in dark and anaerobic environments. They are recognized for the production of diverse low-molecular-weight metabolites crucial to human health and diseases. Carotenoids, low-molecular-weight pigments known for their antioxidative activity, are delivered to humans through oral intake. However, it remains unclear whether human intestinal bacteria biosynthesize carotenoids as part of the in-situ microbiota. In this study, we investigated carotenoid synthesis genes in various human gut and probiotic bacteria. As a result, novel candidates, the crtM and crtN genes, were identified in the carbon monoxide-utilizing gut anaerobe Eubacterium limosum and the lactic acid bacterium Leuconostoc mesenteroides subsp. mesenteroides. These gene candidates were isolated, introduced into Escherichia coli, which synthesized a carotenoid substrate, and cultured aerobically. Structural analysis of the resulting carotenoids revealed that the crtM and crtN gene candidates of E. limosum and L. mesenteroides mediate the production of 4,4'-diaponeurosporene through 15-cis-4,4'-diapophytoene. Evaluation of the crtE-homologous genes in these bacteria indicated their non-functionality for C40-carotenoid production. E. limosum and L. mesenteroides, along with the known carotenogenic lactic acid bacterium Lactiplantibacillus plantarum, were observed to produce no carotenoids under strictly anaerobic conditions. The two lactic acid bacteria synthesized detectable levels of 4,4'-diaponeurosporene under semi-aerobic conditions. The findings highlight that the obligate anaerobe E. limosum retains aerobically functional C30-carotenoid biosynthesis genes, potentially with no immediate self-utility, suggesting an evolutionary direction in carotenoid biosynthesis. (229 words).
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Affiliation(s)
- Wataru Matsumoto
- Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, 1-308, Suematsu, Nonoich-shi 921-8836, Japan
| | - Miho Takemura
- Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, 1-308, Suematsu, Nonoich-shi 921-8836, Japan
| | - Haruka Nanaura
- Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, 1-308, Suematsu, Nonoich-shi 921-8836, Japan
| | - Yuta Ami
- Department of Science and Technology on Food Safety, Kinki University, 930 Nishimitani, Kinokawa, Wakayama 649-6493, Japan
| | - Takashi Maoka
- Research Institute for Production Development, Shimogamo-morimotocho, Sakyo-ku, Kyoto 606-0805, Japan
| | - Kazutoshi Shindo
- Department of Food and Nutrition, Japan Women's University, Mejirodai, Bunkyo-ku, Tokyo 112-8681, Japan
| | - Shin Kurihara
- Department of Science and Technology on Food Safety, Kinki University, 930 Nishimitani, Kinokawa, Wakayama 649-6493, Japan
| | - Norihiko Misawa
- Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, 1-308, Suematsu, Nonoich-shi 921-8836, Japan
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Zhang L, Ma XG. A Comprehensive Review on Biotransformation, Interaction, and Health of Gut Microbiota and Bioactive Components. Comb Chem High Throughput Screen 2024; 27:1551-1565. [PMID: 37916626 DOI: 10.2174/0113862073257733231011072004] [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: 05/02/2023] [Revised: 08/25/2023] [Accepted: 09/06/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND The relationship between gut microbiota and bioactive components has become the research focus in the world. We attempted to clarify the relationship between biotransformation and metabolites of gut microbiota and bioactive components, and explore the metabolic pathway and mechanism of bioactive ingredients in vivo, which will provide an important theoretical basis for the clinical research of bioactive ingredients and rationality of drugs, and also provide an important reference for the development of new drugs with high bioavailability. METHODS The related references of this review on microbiota and bioactive components were collected from both online and offline databases, such as ScienceDirect, PubMed, Elsevier, Willy, SciFinder, Google Scholar, Web of Science, Baidu Scholar, SciHub, Scopus, and CNKI. RESULTS This review summarized the biotransformation of bioactive components under the action of gut microbiota, including flavonoids, terpenoids, phenylpropanoids, alkaloids, steroids, and other compounds. The interaction of bioactive components and gut microbiota is a key link for drug efficacy. Relevant research is crucial to clarify bioactive components and their mechanisms, which involve the complex interaction among bioactive components, gut microbiota, and intestinal epithelial cells. This review also summarized the individualized, precise, and targeted intervention of gut microbiota in the field of intestinal microorganisms from the aspects of dietary fiber, microecological agents, fecal microbiota transplantation, and postbiotics. It will provide an important reference for intestinal microecology in the field of nutrition and health for people. CONCLUSION To sum up, the importance of human gut microbiota in the research of bioactive components metabolism and transformation has attracted the attention of scholars all over the world. It is believed that with the deepening of research, human gut microbiota will be more widely used in the pharmacodynamic basis, drug toxicity relationship, new drug discovery, drug absorption mechanism, and drug transport mechanism in the future.
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Affiliation(s)
- Lin Zhang
- Department of Medical Nursing, Jiyuan Vocational and Technical College, 459000 Jiyuan, Henan, P.R. China
| | - Xiao-Gen Ma
- Department of Medical Nursing, Jiyuan Vocational and Technical College, 459000 Jiyuan, Henan, P.R. China
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Aliya S, Alhammadi M, Park U, Tiwari JN, Lee JH, Han YK, Huh YS. The potential role of formononetin in cancer treatment: An updated review. Biomed Pharmacother 2023; 168:115811. [PMID: 37922652 DOI: 10.1016/j.biopha.2023.115811] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 10/21/2023] [Accepted: 10/26/2023] [Indexed: 11/07/2023] Open
Abstract
Currently, cancer is one of the main research topics, due to its high incidence and drug resistance to existing anti-cancer drugs. Formononetin, a natural product with phytoestrogenic properties and diverse biological functions, has attracted the attention of researchers working on anticancer drugs. Formononetin emerges as an intriguing bioactive substance compared to other isoflavones as it exhibits potent chemotherapeutic activity with less toxicity. Formononetin effectively plays a significant role in inhibiting cell proliferation, invasion, and metastatic abilities of cancer cells by targeting major signaling pathways at the junction of interconnected pathways. It also induces apoptosis and cell cycle arrest by modulating mediator proteins. It causes upregulation of key factors such as p-AKT, p38, p21, and p53 and downregulation of NF-κB. Furthermore, formononetin regulates the neoplastic microenvironment by inactivating the ERK1/2 pathway and lamin A/C signaling and has been reported to inactivate JAK/STAT, PKB or AKT, and mitogen-activated protein kinase pathways and to suppress cell migration, invasion, and angiogenesis in human cancer cells. To assist researchers in further exploring formononetin as a potential anticancer therapeutic candidate, this review focuses on both in vitro and in vivo proof of concept studies, patents, and clinical trials pertinent to formononetin's anticancer properties. Overall, this review discusses formononetin from a comprehensive perspective to highlight its potential benefits as an anticancer agent.
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Affiliation(s)
- Sheik Aliya
- Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Munirah Alhammadi
- Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Uichang Park
- Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Jitendra N Tiwari
- Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 100-715, Republic of Korea
| | - Jeong-Hwan Lee
- 3D Convergence Center, Inha University, Incheon 22212, Republic of Korea; Department of Materials Science and Engineering, Inha University, Incheon 22212, Republic of Korea
| | - Young-Kyu Han
- Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 100-715, Republic of Korea.
| | - Yun Suk Huh
- Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea.
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Li J, Chen Y, Li R, Zhang X, Chen T, Mei F, Liu R, Chen M, Ge Y, Hu H, Wei R, Chen Z, Fan H, Zeng Z, Deng Y, Luo H, Hu S, Cai S, Wu F, Shi N, Wang Z, Zeng Y, Xie M, Jiang Y, Chen Z, Jia W, Chen P. Gut microbial metabolite hyodeoxycholic acid targets the TLR4/MD2 complex to attenuate inflammation and protect against sepsis. Mol Ther 2023; 31:1017-1032. [PMID: 36698311 PMCID: PMC10124078 DOI: 10.1016/j.ymthe.2023.01.018] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 12/08/2022] [Accepted: 01/19/2023] [Indexed: 01/26/2023] Open
Abstract
Sepsis, a critical condition resulting from the systemic inflammatory response to a severe microbial infection, represents a global public health challenge. However, effective treatment or intervention to prevent and combat sepsis is still lacking. Here, we report that hyodeoxycholic acid (HDCA) has excellent anti-inflammatory properties in sepsis. We discovered that the plasma concentration of HDCA was remarkably lower in patients with sepsis and negatively correlated with the severity of the disease. Similar changes in HDCA levels in plasma and cecal content samples were observed in a mouse model of sepsis, and these changes were associated with a reduced abundance of HDCA-producing strains. Interestingly, HDCA administration significantly decreased systemic inflammatory responses, prevented organ injury, and prolonged the survival of septic mice. We demonstrated that HDCA suppressed excessive activation of inflammatory macrophages by competitively blocking lipopolysaccharide binding to the Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 receptor complex, a unique mechanism that characterizes HDCA as an endogenous inhibitor of inflammatory signaling. Additionally, we verified these findings in TLR4 knockout mice. Our study highlights the potential value of HDCA as a therapeutic molecule for sepsis.
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Affiliation(s)
- Jiaxin Li
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Yuqi Chen
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Rui Li
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xianglong Zhang
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Tao Chen
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Fengyi Mei
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Ruofan Liu
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Meiling Chen
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Yue Ge
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Hongbin Hu
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Rongjuan Wei
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Zhenfeng Chen
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Hongying Fan
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - Zhenhua Zeng
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Yongqiang Deng
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Haihua Luo
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Shuiwang Hu
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Shumin Cai
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Feng Wu
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Nengxian Shi
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Zhang Wang
- Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou 510515, China
| | - Yunong Zeng
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Ming Xie
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Yong Jiang
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Zhongqing Chen
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Wei Jia
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China.
| | - Peng Chen
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China.
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Feng ZJ, Lai WF. Chemical and Biological Properties of Biochanin A and Its Pharmaceutical Applications. Pharmaceutics 2023; 15:pharmaceutics15041105. [PMID: 37111591 PMCID: PMC10143291 DOI: 10.3390/pharmaceutics15041105] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 03/03/2023] [Accepted: 03/09/2023] [Indexed: 04/03/2023] Open
Abstract
Biochanin A (BCA), an isoflavone derived from various plants such as chickpea, red clover and soybean, is attracting increasing attention and is considered to have applications in the development of pharmaceuticals and nutraceuticals due to its anti-inflammatory, anti-oxidant, anti-cancer and neuroprotective properties. To design optimised and targeted BCA formulations, on one hand there is a need for more in-depth studies on the biological functions of BCA. On the other hand, further studies on the chemical conformation, metabolic composition and bioavailability of BCA need to be conducted. This review highlights the various biological functions, extraction methods, metabolism, bioavailability, and application prospects of BCA. It is hoped that this review will provide a basis for understanding the mechanism, safety and toxicity of BCA and implementing the development of BCA formulations.
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Affiliation(s)
- Zhen-Jie Feng
- Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong SAR, China
| | - Wing-Fu Lai
- Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong SAR, China
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7
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Langa S, Peirotén Á, Curiel JA, de la Bastida AR, Landete JM. Isoflavone Metabolism by Lactic Acid Bacteria and Its Application in the Development of Fermented Soy Food with Beneficial Effects on Human Health. Foods 2023; 12:1293. [PMID: 36981219 PMCID: PMC10048179 DOI: 10.3390/foods12061293] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/08/2023] [Accepted: 03/16/2023] [Indexed: 03/22/2023] Open
Abstract
Isoflavones are phenolic compounds (considered as phytoestrogens) with estrogenic and antioxidant function, which are highly beneficial for human health, especially in the aged population. However, isoflavones in foods are not bioavailable and, therefore, have low biological activity. Additionally, their transformation into bioactive compounds by microorganisms is necessary to obtain bioavailable isoflavones with beneficial effects on human health. Many lactic acid bacteria (LAB) can transform the methylated and glycosylated forms of isoflavones naturally present in foods into more bioavailable aglycones, such as daidzein, genistein and glycitein. In addition, certain LAB strains are capable of transforming isoflavone aglycones into compounds with a greater biological activity, such as dihydrodaidzein (DHD), O-desmethylangolensin (O-DMA), dihydrogenistein (DHG) and 6-hydroxy-O-desmethylangolensin (6-OH-O-DMA). Moreover, Lactococcus garviae 20-92 is able to produce equol. Another strategy in the bioconversion of isoflavones is the heterologous expression of genes from Slackia isoflavoniconvertens DSM22006, which have allowed the production of DHD, DHG, equol and 5-hydroxy-equol in high concentrations by engineered LAB strains. Accordingly, the consequences of isoflavone metabolism by LAB and its application in the development of foods enriched in bioactive isoflavones, as well as health benefits attributed to their consumption, will be addressed in this work.
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Affiliation(s)
| | | | | | | | - José María Landete
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Carretera de La Coruña Km 7.5, 28040 Madrid, Spain
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8
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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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9
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Son J, Jeong KJ. Engineering of Leuconostoc citreum for Efficient Bioconversion of Soy Isoflavone Glycosides to Their Aglycone Forms. Int J Mol Sci 2022; 23:ijms23179568. [PMID: 36076965 PMCID: PMC9455899 DOI: 10.3390/ijms23179568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/19/2022] [Accepted: 08/22/2022] [Indexed: 11/16/2022] Open
Abstract
Soy isoflavones are phytochemicals that possess various beneficial physiological properties such as anti-aging, anti-tumor, and antioxidant properties. Since soy isoflavones exist in glycoside forms, their bioavailability requires initial hydrolysis of the sugar moieties bound to them to be efficiently absorbed through the gut epithelium. Instead of conventional chemical hydrolysis using acids or organic solvents, alternative strategies for enhancing the bioavailability of soy isoflavones using biological methods are gaining attention. Here, we engineered Leuconostoc citreum isolated from Korean kimchi for efficient bioconversion of soy isoflavone glycosides into their aglycone forms to enhance their bioavailability. We first constructed an expression module based on the isoflavone hydrolase (IH)-encoding gene of Bifidobacterium lactis, which mediates conversion of isoflavone glycosides to aglycone forms. Using a high copy number plasmid and bicistronic expression design, the IH was successfully synthesized in L. citreum. Additionally, we determined enzymatic activity of the IH using an in vivo β-glucosidase assay and confirmed its highly efficient bioconversion efficiency for various types of isoflavone glycosides. Finally, we successfully demonstrated that the engineered L. citreum could convert isoflavone glycosides present in fermented soymilk into aglycones.
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Affiliation(s)
- Jaewoo Son
- Department of Chemical and Biomolecular Engineering, BK21 Plus Program, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea
| | - Ki Jun Jeong
- Department of Chemical and Biomolecular Engineering, BK21 Plus Program, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea
- Institute for The BioCentury, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea
- Correspondence: ; Tel.: +82-42-350-3934
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10
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Rich BE, Jackson JC, de Ora LO, Long ZG, Uyeda KS, Bess EN. Alternative pathway for dopamine production by acetogenic gut bacteria that O-Demethylate 3-Methoxytyramine, a metabolite of catechol O-Methyltransferase. J Appl Microbiol 2022; 133:1697-1708. [PMID: 35737746 PMCID: PMC9544265 DOI: 10.1111/jam.15682] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 06/01/2022] [Accepted: 06/20/2022] [Indexed: 11/27/2022]
Abstract
AIMS The gut microbiota modulates dopamine levels in vivo, but the bacteria and biochemical processes responsible remain incompletely characterized. A potential precursor of bacterial dopamine production is 3-methoxytyramine (3MT); 3MT is produced when dopamine is O-methylated by host catechol O-methyltransferase (COMT), thereby attenuating dopamine levels. This study aimed to identify whether gut bacteria are capable of reverting 3MT to dopamine. METHODS AND RESULTS Human faecal bacterial communities O-demethylated 3MT and yielded dopamine. Gut bacteria that mediate this transformation were identified as acetogens Eubacterium limosum and Blautia producta. Upon exposing these acetogens to propyl iodide, a known inhibitor of cobalamin-dependent O-demethylases, 3MT O-demethylation was inhibited. Culturing E. limosum and B. producta with 3MT afforded increased acetate levels as compared with vehicle controls. CONCLUSIONS Gut bacterial acetogens E. limosum and B. producta synthesized dopamine from 3MT. This O-demethylation of 3MT was likely performed by cobalamin-dependent O-demethylases implicated in reductive acetogenesis. SIGNIFICANCE AND IMPACT OF THE STUDY This is the first report that gut bacteria can synthesize dopamine by O-demethylation of 3MT. Owing to 3MT being the product of host COMT attenuating dopamine levels, gut bacteria that reverse this transformation-converting 3MT to dopamine-may act as a counterbalance for dopamine regulation by COMT.
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Affiliation(s)
- Barry E Rich
- Department of Chemistry, University of California, Irvine, Irvine, California, USA
| | - Jayme C Jackson
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, USA
| | - Lizett Ortiz de Ora
- Department of Chemistry, University of California, Irvine, Irvine, California, USA
| | - Zane G Long
- Department of Chemistry, University of California, Irvine, Irvine, California, USA
| | - Kylie S Uyeda
- Department of Chemistry, University of California, Irvine, Irvine, California, USA
| | - Elizabeth N Bess
- Department of Chemistry, University of California, Irvine, Irvine, California, USA.,Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, USA
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11
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Curiel JA, Landete JM. Identification and cloning of the first O-demethylase gene of isoflavones from Bifidobacterium breve INIA P734. Lebensm Wiss Technol 2022. [DOI: 10.1016/j.lwt.2022.113510] [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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Melo AMD, Barbi RCT, Costa BP, Ikeda M, Carpiné D, Ribani RH. Valorization of the agro-industrial by-products of bacupari (Garcinia brasiliensis (Mart.)) through production of flour with bioactive properties. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2021.101343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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13
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The MttB superfamily member MtyB from the human gut symbiont Eubacterium limosum is a cobalamin-dependent γ-butyrobetaine methyltransferase. J Biol Chem 2021; 297:101327. [PMID: 34688665 PMCID: PMC8604678 DOI: 10.1016/j.jbc.2021.101327] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 10/05/2021] [Accepted: 10/06/2021] [Indexed: 12/12/2022] Open
Abstract
The production of trimethylamine (TMA) from quaternary amines such as l-carnitine or γ-butyrobetaine (4-(trimethylammonio)butanoate) by gut microbial enzymes has been linked to heart disease. This has led to interest in enzymes of the gut microbiome that might ameliorate net TMA production, such as members of the MttB superfamily of proteins, which can demethylate TMA (e.g., MttB) or l-carnitine (e.g., MtcB). Here, we show that the human gut acetogen Eubacterium limosum demethylates γ-butyrobetaine and produces MtyB, a previously uncharacterized MttB superfamily member catalyzing the demethylation of γ-butyrobetaine. Proteomic analyses of E. limosum grown on either γ-butyrobetaine or dl-lactate were employed to identify candidate proteins underlying catabolic demethylation of the growth substrate. Three proteins were significantly elevated in abundance in γ-butyrobetaine-grown cells: MtyB, MtqC (a corrinoid-binding protein), and MtqA (a corrinoid:tetrahydrofolate methyltransferase). Together, these proteins act as a γ-butyrobetaine:tetrahydrofolate methyltransferase system, forming a key intermediate of acetogenesis. Recombinant MtyB acts as a γ-butyrobetaine:MtqC methyltransferase but cannot methylate free cobalamin cofactor. MtyB is very similar to MtcB, the carnitine methyltransferase, but neither was detectable in cells grown on carnitine nor was detectable in cells grown with γ-butyrobetaine. Both quaternary amines are substrates for either enzyme, but kinetic analysis revealed that, in comparison to MtcB, MtyB has a lower apparent Km for γ-butyrobetaine and higher apparent Vmax, providing a rationale for MtyB abundance in γ-butyrobetaine-grown cells. As TMA is readily produced from γ-butyrobetaine, organisms with MtyB-like proteins may provide a means to lower levels of TMA and proatherogenic TMA-N-oxide via precursor competition.
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14
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Ford HR, Busato S, Trevisi E, Muchiri RN, van Breemen RB, Bionaz M, Ates S. Effects of Pasture Type on Metabolism, Liver and Kidney Function, Antioxidant Status, and Plant Secondary Compounds in Plasma of Grazing, Jersey Dairy Cattle During Mid-lactation. FRONTIERS IN ANIMAL SCIENCE 2021. [DOI: 10.3389/fanim.2021.729423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Some pasture species are rich in phytochemicals, able to improve milk yield and quality and to reduce the environmental impacts of livestock farming. The phytochemicals interact with the different gene networks within the animal, such as nuclear factor erythroid 2-related factor 2 (NRF2), but their overall impact on animal health remains to be fully understood. The objective of this study was to identify the effects of pasture Legumes and non-leguminous Forbs containing high bioactive compounds on metabolism and activity of the liver, antioxidant response, kidney function, and inflammation of dairy cows using a large array of blood parameters associated with metabolism and the innate immune system. For this purpose, 26 parameters and the concentration of certain bioactive compounds were assessed in blood plasma, collected from the Jersey cows grazing either Grass, Legume, or Forb-based pastures. In addition, serum collected from all the cows was utilized to detect the changes in NRF2 activation in bovine mammary alveolar cells (MACT) and hepatocytes. Compared with Grass, the cows that grazed both Forb and Legume pastures had lower β-hydroxybutyric acid (BHB) and creatinine and larger vitamin E and the ferric reducing ability of the plasma, supporting an improved antioxidative status for these animals. Compared with both Grass and Legume, the cows that graze Forb pasture had lower urea and urea to creatinine ratio, and lower creatinine, indicating a better kidney function. The cows grazing Legume pasture had greater hematocrit, bilirubin, cholesterol, albumin, β-carotene, retinol, and thiol groups but lower ceruloplasmin, paraoxonase, and myeloperoxidase (MPO) than those grazed Grass and Forb pastures, indicating a positive effect of Legume pasture on the liver, oxidative stress, and red blood cells. The plasma of cows in the various pastures was enriched with various isoflavonoids, especially the cows grazed on Forb and Legume pastures, which likely contributed to improving the antioxidative status of those cows. However, this effect was likely not due to the higher activation of NRF2. Overall, these results indicate that Forb and Legume pastures rich in secondary metabolites do not strongly affect the metabolism but can improve the status of the liver and the kidney and improve the efficiency of N utilization and antioxidant response, compared with the Grass pasture.
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15
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Xia H. Extensive metabolism of flavonoids relevant to their potential efficacy on Alzheimer's disease. Drug Metab Rev 2021; 53:563-591. [PMID: 34491868 DOI: 10.1080/03602532.2021.1977316] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Alzheimer's disease (AD) is an age-related neurodegenerative disorder, the incidence of which is climbing with ever-growing aged population, but no cure is hitherto available. The epidemiological studies unveiled that chronic intake of flavonoids was negatively associated with AD risk. Flavonoids, a family of natural polyphenols widely distributed in human daily diets, were readily conjugated by phase II drug metabolizing enzymes after absorption in vivo, and glucuronidation could occur in 1 min following intravenous administration. Recently, as many as 191 metabolites were obtained after intragastric administration of a single flavonoid, indicating that other bioactive metabolites, besides conjugates, might be formed and account for the contradiction between efficacy of flavonoids in human or animal models and low systematic exposure of flavonoid glycosides or aglycones. In this review, metabolism of complete 68 flavonoid monomers potential for AD treatment, grouped in flavonoid O-glycosides, flavonoid aglycones, flavonoid C-glycosides, flavonoid dimers, flavonolignans and prenylated flavonoids according to their common structural elements, respectively, has been systematically retrospected, summarized and discussed, including their unequivocally identified metabolites, metabolic interconversions, metabolic locations, metabolic sites (regio- or stereo-selectivity), primarily involved metabolic enzymes or intestinal bacteria, and interspecies correlations or differences in metabolism, and their bioactive metabolites and the underlying mechanism to reverse AD pathology were also reviewed, providing whole perspective about advances on extensive metabolism of diverse potent flavonoids in vivo and in vitro up to date and aiming at elucidation of mechanism of actions of flavonoids on AD or other central nervous system (CNS) disorders.
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Affiliation(s)
- Hongjun Xia
- Medical College, Yangzhou University, Yangzhou, People's Republic of China
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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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Landi N, Piccolella S, Ragucci S, Faramarzi S, Clemente A, Papa S, Pacifico S, Di Maro A. Valle Agricola Chickpeas: Nutritional Profile and Metabolomics Traits of a Typical Landrace Legume from Southern Italy. Foods 2021; 10:foods10030583. [PMID: 33802023 PMCID: PMC8002183 DOI: 10.3390/foods10030583] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 02/25/2021] [Accepted: 03/05/2021] [Indexed: 11/29/2022] Open
Abstract
Chickpea (Cicer arietinum L.) from Valle Agricola is a legume cultivated in Southern Italy whose intake is strictly linked to rural traditions. In order to get new biochemical insight on this landrace and to promote its consumption and marketing, nutritional values (moisture content, total proteins, lipids, total and free amino acids) and metabolic traits are deeply investigated. Valle Agricola chickpea is nutritionally rich in proteins (19.70 g/100 g) and essential amino acids (7.12 g/100 g; ~40% of total). Carbohydrates, whose identity was unraveled by means of UHPLC-HR MS/MS analysis, were almost 60% of chemicals. In particular, a di-galactosylglycerol, a pinitol digalactoside, and a galactosylciceritol were found as constitutive, together with different raffinose-series oligosaccharides. Although lipids were the less constitutive compounds, glycerophospholipids were identified, while among free fatty acids linoleic acid (C18:2) was the most abundant, followed by oleic (C18:1) and palmitic (C16:0) acids. Isoflavones and hydroxybenzoic acid derivatives were also detected. Valle Agricola chickpeas showed very good levels of several mineral nutrients, especially magnesium (164 mg/100 g), potassium (748 mg/100 g), calcium (200 mg/100 g), zinc (4.20 mg/100 g) and manganese (0.45 mg/100 g). The boiling process favorably decreases anti-trypsin and anti-chymotrypsin activities, depleting this precious seed of its intrinsic antinutritional factors.
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18
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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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19
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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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20
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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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21
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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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22
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Shin J, Kang S, Song Y, Jin S, Lee JS, Lee JK, Kim DR, Kim SC, Cho S, Cho BK. Genome Engineering of Eubacterium limosum Using Expanded Genetic Tools and the CRISPR-Cas9 System. ACS Synth Biol 2019; 8:2059-2068. [PMID: 31373788 DOI: 10.1021/acssynbio.9b00150] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Eubacterium limosum is one of the important bacteria in C1 feedstock utilization as well as in human gut microbiota. Although E. limosum has recently garnered much attention and investigation on a genome-wide scale, a bottleneck for systematic engineering in E. limosum is the lack of available genetic tools and an efficient genome editing platform. To overcome this limitation, we here report expanded genetic tools and the CRISPR-Cas9 system. We have developed an inducible promoter system that enables implementation of the CRISPR-Cas9 system to precisely manipulate target genes of the Wood-Ljungdahl pathway with 100% efficiency. Furthermore, we exploited the effectiveness of CRISPR interference to reduce the expression of target genes, exhibiting substantial repression of several genes in the Wood-Ljungdahl pathway and fructose-PTS system. These expanded genetic tools and CRISPR-Cas9 system comprise powerful and widely applicable genetic tools to accelerate functional genomic study and genome engineering in E. limosum.
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Affiliation(s)
- Jongoh Shin
- Department of Biological Sciences and KI for the BioCentury , KAIST , Daejeon , 305-701 , Republic of Korea
| | - Seulgi Kang
- Department of Biological Sciences and KI for the BioCentury , KAIST , Daejeon , 305-701 , Republic of Korea
| | - Yoseb Song
- Department of Biological Sciences and KI for the BioCentury , KAIST , Daejeon , 305-701 , Republic of Korea
| | - Sangrak Jin
- Department of Biological Sciences and KI for the BioCentury , KAIST , Daejeon , 305-701 , Republic of Korea
| | - Jin Soo Lee
- Department of Biological Sciences and KI for the BioCentury , KAIST , Daejeon , 305-701 , Republic of Korea
| | - Jung-Kul Lee
- Department of Chemical Engineering , Konkuk University , Seoul , 05029 , Republic of Korea
| | - Dong Rip Kim
- Department of Mechanical Engineering , Hanyang University , Seoul , 04763 , Republic of Korea
| | - Sun Chang Kim
- Department of Biological Sciences and KI for the BioCentury , KAIST , Daejeon , 305-701 , Republic of Korea
- Intelligent Synthetic Biology Center , Daejeon , 305-701 , Republic of Korea
| | - Suhyung Cho
- Department of Biological Sciences and KI for the BioCentury , KAIST , Daejeon , 305-701 , Republic of Korea
| | - Byung-Kwan Cho
- Department of Biological Sciences and KI for the BioCentury , KAIST , Daejeon , 305-701 , Republic of Korea
- Intelligent Synthetic Biology Center , Daejeon , 305-701 , Republic of Korea
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23
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Ahn-Jarvis JH, Parihar A, Doseff AI. Dietary Flavonoids for Immunoregulation and Cancer: Food Design for Targeting Disease. Antioxidants (Basel) 2019; 8:E202. [PMID: 31261915 PMCID: PMC6680729 DOI: 10.3390/antiox8070202] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 06/25/2019] [Accepted: 06/26/2019] [Indexed: 12/13/2022] Open
Abstract
Flavonoids, one of the most abundant phytochemicals in a diet rich in fruits and vegetables, have been recognized as possessing anti-proliferative, antioxidant, anti-inflammatory, and estrogenic activities. Numerous cellular and animal-based studies show that flavonoids can function as antioxidants by preventing DNA damage and scavenging reactive oxygen radicals, inhibiting formation of DNA adducts, enhancing DNA repair, interfering with chemical damage by induction of Phase II enzymes, and modifying signaling pathways. Recent evidence also shows their ability to regulate the immune system. However, findings from clinical trials have been mixed with no clear consensus on dose, frequency, or type of flavonoids best suited to elicit many of the beneficial effects. Delivery of these bioactive compounds to their biological targets through "targeted designed" food processing strategies is critical to reach effective concentration in vivo. Thus, the identification of novel approaches that optimize flavonoid bioavailability is essential for their successful clinical application. In this review, we discuss the relevance of increasing flavonoid bioavailability, by agricultural engineering and "targeted food design" in the context of the immune system and cancer.
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Affiliation(s)
| | - Arti Parihar
- Department of Science, Bellingham Technical College, WA, 98225, USA
| | - Andrea I Doseff
- Department of Physiology and Department of Pharmacology & Toxicology, Michigan State University, MI, 48864, USA.
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24
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Wu XM, Tan RX. Interaction between gut microbiota and ethnomedicine constituents. Nat Prod Rep 2019; 36:788-809. [DOI: 10.1039/c8np00041g] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This highlight reviews the interaction processes between gut microbiota and ethnomedicine constituents, which may conceptualize future therapeutic strategies.
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Affiliation(s)
- Xue Ming Wu
- State Key Laboratory Cultivation Base for TCM Quality and Efficacy
- Nanjing University of Chinese Medicine
- Nanjing
- China
| | - Ren Xiang Tan
- State Key Laboratory Cultivation Base for TCM Quality and Efficacy
- Nanjing University of Chinese Medicine
- Nanjing
- China
- State Key Laboratory of Pharmaceutical Biotechnology
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25
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Flavonoids and Colorectal Cancer Prevention. Antioxidants (Basel) 2018; 7:antiox7120187. [PMID: 30544686 PMCID: PMC6316869 DOI: 10.3390/antiox7120187] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 11/03/2018] [Accepted: 12/04/2018] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer, but despite advances in treatment, it remains the second most common cause of cancer-related mortality. Prevention may, therefore, be a key strategy in reducing colorectal cancer deaths. Given reports of an inverse association between fruit and vegetable consumption with colorectal cancer risk, there has been significant interest in understanding the metabolism and bioactivity of flavonoids, which are highly abundant in fruits and vegetables and account for their pigmentation. In this review, we discuss host and microbiota-mediated metabolism of flavonoids and the potential mechanisms by which flavonoids can exert protective effects against colon tumorigenesis, including regulation of signaling pathways involved in apoptosis, cellular proliferation, and inflammation and modulation of the gut microbiome.
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26
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Paraiso IL, Plagmann LS, Yang L, Zielke R, Gombart AF, Maier CS, Sikora AE, Blakemore PR, Stevens JF. Reductive Metabolism of Xanthohumol and 8-Prenylnaringenin by the Intestinal Bacterium Eubacterium ramulus. Mol Nutr Food Res 2018; 63:e1800923. [PMID: 30471194 DOI: 10.1002/mnfr.201800923] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 11/14/2018] [Indexed: 12/16/2022]
Abstract
SCOPE The intestinal microbiota transforms a wide range of available substrates, including polyphenols. Microbial catabolites of polyphenols can contribute in significant ways to the health-promoting properties of their parent polyphenols. This work aims to identify intestinal metabolites of xanthohumol (XN), a prenylated flavonoid found in hops (Humulus lupulus) and beer, as well as to identify pathways of metabolism of XN in the gut. METHODS AND RESULTS To investigate intestinal metabolism, XN and related prenylated flavonoids, isoxanthohumol (IX), and 8-prenylnaringenin (8PN) were added to growing cultures of intestinal bacteria, Eubacterium ramulus and E. limosum. Liquid chromatography coupled with mass spectrometry was used to identify metabolites of the flavonoids from the cultures. The metabolic capacity of E. limosum appears to be limited to O-demethylation. Evidence from the study indicates that E. ramulus hydrogenates XN to form α,β-dihydroxanthohumol (DXN) and metabolizes the potent phytoestrogen 8PN into the chalcones, O-desmethylxanthohumol (DMX) and O-desmethyl-α,β-dihydroxanthohumol (DDXN). CONCLUSION Microbial metabolism is likely to affect both activity and toxicity of XN and derivatives. This study along with others highlights that attention should be focused on metabolites, in particular, products of intestinal microbial metabolism.
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Affiliation(s)
- Ines L Paraiso
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331, USA.,Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA
| | - Layhna S Plagmann
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.,Department of Chemistry, Oregon State University, Corvallis, OR, 97331, USA
| | - Liping Yang
- Department of Chemistry, Oregon State University, Corvallis, OR, 97331, USA
| | - Ryszard Zielke
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331, USA
| | - Adrian F Gombart
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.,Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, 97331, USA
| | - Claudia S Maier
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.,Department of Chemistry, Oregon State University, Corvallis, OR, 97331, USA
| | - Aleksandra E Sikora
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331, USA.,Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA
| | - Paul R Blakemore
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.,Department of Chemistry, Oregon State University, Corvallis, OR, 97331, USA
| | - Jan F Stevens
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331, USA.,Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA
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Williamson G, Kay CD, Crozier A. The Bioavailability, Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective. Compr Rev Food Sci Food Saf 2018; 17:1054-1112. [DOI: 10.1111/1541-4337.12351] [Citation(s) in RCA: 377] [Impact Index Per Article: 53.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 03/13/2018] [Accepted: 03/14/2018] [Indexed: 12/27/2022]
Affiliation(s)
| | - Colin D. Kay
- Food Bioprocessing and Nutrition Sciences, Plants for Human Health Inst. North Carolina State Univ. North Carolina Research Campus Kannapolis NC 28081 U.S.A
| | - Alan Crozier
- Dept. of Nutrition Univ. of California Davis CA 95616 U.S.A
- School of Medicine Dentistry and Nursing, Univ. Glasgow Glasgow G12 8QQ UK
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28
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Gaya P, Peirotén Á, Landete JM. Transformation of plant isoflavones into bioactive isoflavones by lactic acid bacteria and bifidobacteria. J Funct Foods 2017. [DOI: 10.1016/j.jff.2017.10.029] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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Determination of the Genome and Primary Transcriptome of Syngas Fermenting Eubacterium limosum ATCC 8486. Sci Rep 2017; 7:13694. [PMID: 29057933 PMCID: PMC5651825 DOI: 10.1038/s41598-017-14123-3] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 10/03/2017] [Indexed: 01/05/2023] Open
Abstract
Autotrophic conversion of CO2 to value-added biochemicals has received considerable attention as a sustainable route to replace fossil fuels. Particularly, anaerobic acetogenic bacteria are naturally capable of reducing CO2 or CO to various metabolites. To fully utilize their biosynthetic potential, an understanding of acetogenesis-related genes and their regulatory elements is required. Here, we completed the genome sequence of the syngas fermenting Eubacterium limosum ATCC 8486 and determined its transcription start sites (TSS). We constructed a 4.4 Mb long circular genome with a GC content of 47.2% and 4,090 protein encoding genes. To understand the transcriptional and translational regulation, the primary transcriptome was augmented, identifying 1,458 TSSs containing a high pyrimidine (T/C) and purine nucleotide (A/G) content at the −1 and +1 position, respectively, along with 1,253 5′-untranslated regions, and principal promoter elements such as −10 (TATAAT) and −35 (TTGACA), and Shine-Dalgarno motifs (GGAGR). Further analysis revealed 93 non-coding RNAs, including one for potential transcriptional regulation of the hydrogenase complex via interaction with molybdenum or tungsten cofactors, which in turn controls formate dehydrogenase activity of the initial step of Wood-Ljungdahl pathway. Our results provide comprehensive genomic information for strain engineering to enhance the syngas fermenting capacity of acetogenic bacteria.
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Chadha R, Bhalla Y, Jain A, Chadha K, Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. Nat Prod Commun 2017. [DOI: 10.1177/1934578x1701200439] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Soy, a major component of the diet for centuries contains the largest concentration of isoflavones, a class of phytoestrogens. A variety of health benefits are associated with the consumption of soy primarily because of the isoflavones genistein, daidzein, and glycitein with a potential protective effect against a number of chronic diseases. Owing to the pharmaceutical and nutraceutical properties allied with isoflavonoids and their use in functional foods, there is a growing interest in these compounds. This review throws light on the chemistry, and significant pharmacological and biopharmaceutical aspects of soy isoflavones. This article critically describes the mechanisms of action, infers conclusions and shows opportunity for future research.
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Affiliation(s)
- Renu Chadha
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Yashika Bhalla
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Ankita Jain
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Kunal Chadha
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Maninder Karan
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
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31
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Kay CD, Pereira-Caro G, Ludwig IA, Clifford MN, Crozier A. Anthocyanins and Flavanones Are More Bioavailable than Previously Perceived: A Review of Recent Evidence. Annu Rev Food Sci Technol 2017; 8:155-180. [PMID: 28125348 DOI: 10.1146/annurev-food-030216-025636] [Citation(s) in RCA: 199] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
This review considers recent investigations on the bioavailability of anthocyanins and flavanones. Both flavonoids are significant dietary components and are considered to be poorly bioavailable, as only low levels of phase II metabolites appear in the circulatory system and are excreted in urine. However, when lower molecular weight phenolic and aromatic ring-fission catabolites, produced primarily by the action of the colonic microbiota, are taken into account, it is evident that anthocyanins and flavanones are much more bioavailable than previously envisaged. The metabolic events to which these flavonoids are subjected as they pass along the gastrointestinal tract and are absorbed into the circulatory system prior to their rapid elimination by renal excretion are highlighted. Studies on the impact of other food components and the probiotic intake on flavonoid bioavailability are summarized, as is the bioactivity of metabolites and catabolites assayed using a variety of in vitro model systems.
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Affiliation(s)
- Colin D Kay
- Food Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, North Carolina Research Campus, Kannapolis, North Carolina 28081
| | - Gema Pereira-Caro
- Andalusian Institute of Agricultural and Fishery Research and Training, IFAPA, Alameda del Obispo, 14004 Córdoba, Spain
| | - Iziar A Ludwig
- Department of Food Technology, Universitat de Lleida, 25198 Lleida, Spain
| | - Michael N Clifford
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 5XH, Surrey, United Kingdom
| | - Alan Crozier
- Department of Nutrition, University of California, Davis, California 95616-5270;
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Catabolism of citrus flavanones by the probiotics Bifidobacterium longum and Lactobacillus rhamnosus. Eur J Nutr 2016; 57:231-242. [PMID: 27722779 DOI: 10.1007/s00394-016-1312-z] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 11/22/2015] [Indexed: 12/17/2022]
Abstract
PURPOSE Orange juice (OJ) flavanones undergo limited absorption in the upper gastrointestinal tract and reach the colon where they are transformed by the microbiota prior to absorption. This study investigated the ability of two probiotic bacteria, Bifidobacterium longum R0175 and Lactobacillus rhamnosus subsp. Rhamnosus NCTC 10302 to catabolise OJ flavanones. METHODS The bacteria were incubated with hesperetin-7-O-rutinoside, naringenin-7-O-rutinoside, hesperetin and naringenin, and the culture medium and intracellular cell extracts were collected at intervals over a 48 h of incubation period. The flavanones and their phenolic acid catabolites were identified and quantified by HPLC-HR-MS. RESULTS Both probiotics were able to subject hesperetin to ring fission yielding 3-(3'-hydroxy-4'-methoxyphenyl)propionic acid which was subsequently demethylated producing 3-(3',4'-dihydroxyphenyl)propionic acid and then via successive dehydroxylations converted to 3-(3'-hydroxyphenyl)propionic acid and 3-(phenyl)propionic acid. Incubation of both bacteria with naringenin resulted in its conversion to 3-(4'-hydroxyphenyl)propionic acid which underwent dehydroxylation yielding 3-(phenyl)propionic acid. In addition, only L. rhamnosus exhibited rhamnosidase and glucosidase activity and unlike B. longum, which was able to convert hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside to their respective aglycones. The aglycones were then subjected to ring fission and further catabolised in a similar manner to that described above. The flavanones and their catabolites were found in the culture medium but not accumulated in the bacterial cells. CONCLUSIONS These findings demonstrate the enzymatic potential of single strains of bifidobacterium and lactobacillus which may be involved in the colonic catabolism of OJ flavanones in vivo.
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Zafar S, Ahmed R, Khan R. Biotransformation: a green and efficient way of antioxidant synthesis. Free Radic Res 2016; 50:939-48. [PMID: 27383446 DOI: 10.1080/10715762.2016.1209745] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Antioxidant compounds play a vital role in human physiology. They prevent the oxidation of biomolecules by scavenging free radicals produced during physiochemical processes and/or as a result of several pathological states. A balance between the reactive oxygen species (free radicals) and antioxidants is essential for proper physiological conditions. Excessive free radicals cause oxidative stress which can lead to several human diseases. Therefore, synthesis of the effective antioxidants is crucial in managing the oxidative stress. Biotransformation has evolved as an effective technique for the production of structurally diverse molecules with a wide range of biological activities. This methodology surpasses the conventional chemical synthesis due to the fact that enzymes, being specific in nature, catalyze reactions affording products with excellent regio- and stereoselectivities. Structural transformation of various classes of compounds such as alkaloids, steroids, flavonoids, and terpenes has been carried out through this technique. Several bioactive molecules, especially those having antioxidant potential have also been synthesized by using different biotransformation techniques and enzymes. Hydroxylated, glycosylated, and acylated derivatives of phenols, flavonoids, cinnamates, and other molecules have proven abilities as potential antioxidants. A critical review of the biotransformation of these compounds into potent antioxidant metabolites is presented here.
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Affiliation(s)
- Salman Zafar
- a Institute of Chemical Sciences, University of Peshawar , Peshawar , Pakistan
| | - Rida Ahmed
- b Department of Basic Sciences , DHA Suffa University, DG-78, Off Khayaban-e-Tufail, Phase VII Ext. Defence Housing Authority , Karachi , Pakistan
| | - Rasool Khan
- a Institute of Chemical Sciences, University of Peshawar , Peshawar , Pakistan
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Braune A, Blaut M. Bacterial species involved in the conversion of dietary flavonoids in the human gut. Gut Microbes 2016; 7:216-34. [PMID: 26963713 PMCID: PMC4939924 DOI: 10.1080/19490976.2016.1158395] [Citation(s) in RCA: 315] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 02/19/2016] [Indexed: 02/03/2023] Open
Abstract
The gut microbiota plays a crucial role in the conversion of dietary flavonoids and thereby affects their health-promoting effects in the human host. The identification of the bacteria involved in intestinal flavonoid conversion has gained increasing interest. This review summarizes available information on the so far identified human intestinal flavonoid-converting bacterial species and strains as well as their enzymes catalyzing the underlying reactions. The majority of described species involved in flavonoid transformation are capable of carrying out the O-deglycosylation of flavonoids. Other bacteria cleave the less common flavonoid-C-glucosides and/or further degrade the aglycones of flavonols, flavanonols, flavones, flavanones, dihydrochalcones, isoflavones and monomeric flavan-3-ols. To increase the currently limited knowledge in this field, identification of flavonoid-converting bacteria should be continued using culture-dependent screening or isolation procedures and molecular approaches based on sequence information of the involved enzymes.
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Affiliation(s)
- Annett Braune
- Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Michael Blaut
- Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
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Kawada Y, Yokoyama S, Yanase E, Niwa T, Suzuki T. The production of S-equol from daidzein is associated with a cluster of three genes in Eggerthella sp. YY7918. BIOSCIENCE OF MICROBIOTA FOOD AND HEALTH 2016; 35:113-21. [PMID: 27508112 PMCID: PMC4965515 DOI: 10.12938/bmfh.2015-023] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Accepted: 03/02/2016] [Indexed: 01/28/2023]
Abstract
Daidzein (DZN) is converted to equol (EQL) by intestinal bacteria. We previously reported that
Eggerthella sp. YY7918, which is found in human feces, is an EQL-producing bacterium and
analyzed its whole genomic sequence. We found three coding sequences (CDSs) in this bacterium that showed 99%
similarity to the EQL-producing enzymes of Lactococcus sp. 20-92. These identified CDSs were
designated eqlA, eqlB, and eqlC and thought to encode
daidzein reductase (DZNR), dihydrodaidzein reductase (DHDR), and tetrahydrodaidzein reductase (THDR),
respectively. These genes were cloned into pColdII. Recombinant plasmids were then introduced into
Escherichia coli BL21 (DE3) and DZNR, DHDR, and THDR were expressed and purified by
6×His-Tag chromatography. We confirmed that these three enzymes were involved in the conversion of DZN to EQL.
Purified DZNR converted DZN to dihydrodaizein (DHD) in the presence of NADPH. DHDR converted DHD to
tetrahydrodaizein (THD) in the presence of NADPH. Neither enzyme showed activities with NADH. THDR converted
THD in the absence of cofactors, NAD(P)H, and also produced DHD as a by-product. Thus, we propose that THDR is
not a reductase but a new type of dismutase. The GC content of these clusters was 64%, similar to the overall
genomic GC content for Eggerthella and Coriobacteriaceae (56–60%), and higher than that for
Lactococcus garvieae (39%), even though the gene cluster showed 99% similarity to that in
Lactococcus sp. 20-92. Taken together, our results indicate that the gene cluster
associated with EQL production evolved in high-GC bacteria including Coriobacteriaceae and was then laterally
transferred to Lactococcus sp. 20-92.
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Affiliation(s)
- Yuika Kawada
- The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Shinichiro Yokoyama
- Department of Food Technology, Industrial Technology Center, Gifu Prefectural Government, 47 Kitaoyobi, Kasamatsu, Hashima, Gifu 501-6064, Japan
| | - Emiko Yanase
- Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Toshio Niwa
- Faculty of Health and Nutrition, Shubun University, 6 Nikko-cho, Ichinomiya, Aichi 491-0938, Japan
| | - Tohru Suzuki
- Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
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Kelly WJ, Henderson G, Pacheco DM, Li D, Reilly K, Naylor GE, Janssen PH, Attwood GT, Altermann E, Leahy SC. The complete genome sequence of Eubacterium limosum SA11, a metabolically versatile rumen acetogen. Stand Genomic Sci 2016; 11:26. [PMID: 26981167 PMCID: PMC4791908 DOI: 10.1186/s40793-016-0147-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2015] [Accepted: 03/07/2016] [Indexed: 12/22/2022] Open
Abstract
Acetogens are a specialized group of anaerobic bacteria able to produce acetate from CO2 and H2 via the Wood-Ljungdahl pathway. In some gut environments acetogens can compete with methanogens for H2, and as a result rumen acetogens are of interest in the development of microbial approaches for methane mitigation. The acetogen Eubacterium limosum SA11 was isolated from the rumen of a New Zealand sheep and its genome has been sequenced to examine its potential application in methane mitigation strategies, particularly in situations where hydrogenotrophic methanogens are inhibited resulting in increased H2 levels in the rumen. The 4.15 Mb chromosome of SA11 has an average G + C content of 47 %, and encodes 3805 protein-coding genes. There is a single prophage inserted in the chromosome, and several other gene clusters appear to have been acquired by horizontal transfer. These include genes for cell wall glycopolymers, a type VII secretion system, cell surface proteins and chemotaxis. SA11 is able to use a variety of organic substrates in addition to H2/CO2, with acetate and butyrate as the principal fermentation end-products, and genes involved in these metabolic pathways have been identified. An unusual feature is the presence of 39 genes encoding trimethylamine methyltransferase family proteins, more than any other bacterial genome. Overall, SA11 is a metabolically versatile organism, but its ability to grow on such a wide range of substrates suggests it may not be a suitable candidate to take the place of hydrogen-utilizing methanogens in the rumen.
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Affiliation(s)
- William J. Kelly
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Gemma Henderson
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Diana M. Pacheco
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Dong Li
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Kerri Reilly
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Graham E. Naylor
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Peter H. Janssen
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Graeme T. Attwood
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Eric Altermann
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
| | - Sinead C. Leahy
- Rumen Microbiology, Animal Science, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North, 4442 New Zealand
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Sudha N, Sameena Y, Enoch IVMV. β-Cyclodextrin Encapsulates Biochanin A and Influences its Binding to Bovine Serum Albumin: Alteration of the Binding Strength. J SOLUTION CHEM 2016. [DOI: 10.1007/s10953-016-0446-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Ozdal T, Sela DA, Xiao J, Boyacioglu D, Chen F, Capanoglu E. The Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility. Nutrients 2016; 8:78. [PMID: 26861391 PMCID: PMC4772042 DOI: 10.3390/nu8020078] [Citation(s) in RCA: 520] [Impact Index Per Article: 57.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 01/11/2016] [Indexed: 02/07/2023] Open
Abstract
As of late, polyphenols have increasingly interested the scientific community due to their proposed health benefits. Much of this attention has focused on their bioavailability. Polyphenol-gut microbiota interactions should be considered to understand their biological functions. The dichotomy between the biotransformation of polyphenols into their metabolites by gut microbiota and the modulation of gut microbiota composition by polyphenols contributes to positive health outcomes. Although there are many studies on the in vivo bioavailability of polyphenols, the mutual relationship between polyphenols and gut microbiota is not fully understood. This review focuses on the biotransformation of polyphenols by gut microbiota, modulation of gut microbiota by polyphenols, and the effects of these two-way mutual interactions on polyphenol bioavailability, and ultimately, human health.
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Affiliation(s)
- Tugba Ozdal
- Department of Food Engineering, Faculty of Engineering and Architecture, Okan Univesity, Tuzla, Istanbul TR-34959, Turkey.
| | - David A Sela
- Department of Food Science, University of Massachusetts Amherst, Amherst, MA 01003, USA.
| | - Jianbo Xiao
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macau, China.
| | - Dilek Boyacioglu
- Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, Istanbul TR-34469, Turkey.
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, China Agricultural University, Beijing 100083, China.
| | - Esra Capanoglu
- Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, Istanbul TR-34469, Turkey.
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Nie Q, Xing M, Hu J, Hu X, Nie S, Xie M. Metabolism and health effects of phyto-estrogens. Crit Rev Food Sci Nutr 2015; 57:2432-2454. [DOI: 10.1080/10408398.2015.1077194] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Qixing Nie
- State Key Laboratory of Food Science and Technology, Nanchang University Nanchang, CN, Nanchang, China
| | - Mengmeng Xing
- State Key Laboratory of Food Science and Technology, Nanchang University Nanchang, CN, Nanchang, China
| | - Jielun Hu
- State Key Laboratory of Food Science and Technology, Nanchang University Nanchang, CN, Nanchang, China
| | - Xiaojuan Hu
- State Key Laboratory of Food Science and Technology, Nanchang University Nanchang, CN, Nanchang, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Technology, Nanchang University Nanchang, CN, Nanchang, China
| | - Mingyong Xie
- State Key Laboratory of Food Science and Technology, Nanchang University Nanchang, CN, Nanchang, China
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Biotransformations and biological activities of hop flavonoids. Biotechnol Adv 2015; 33:1063-90. [PMID: 25708386 DOI: 10.1016/j.biotechadv.2015.02.009] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 02/13/2015] [Accepted: 02/16/2015] [Indexed: 12/13/2022]
Abstract
Female hop cones are used extensively in the brewing industry, but there is now increasing interest in possible uses of hops for non-brewing purposes, especially in the pharmaceutical industry. Among pharmaceutically important compounds from hops are flavonoids, having proven anticarcinogenic, antioxidant, antimicrobial, anti-inflammatory and estrogenic effects. In this review we aim to present current knowledge on the biotransformation of flavonoids from hop cones with respect to products, catalysis and conversion. A list of microbial enzymatic reactions associated with gastrointestinal microbiota is presented. A comparative analysis of the biological activities of hop flavonoids and their biotransformation products is described, indicating where further research has potential for applications in the pharmaceutical industry.
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Draft Genome Sequence of Chemolithoautotrophic Acetogenic Butanol-Producing Eubacterium limosum ATCC 8486. GENOME ANNOUNCEMENTS 2015; 3:3/1/e01564-14. [PMID: 25676768 PMCID: PMC4333668 DOI: 10.1128/genomea.01564-14] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Eubacterium limosum ATCC 8486 is an anaerobic chemolithoautotrophic acetogenic bacterium that converts and transforms syngas and isoflavonoids to butanol and phytoestrogens, respectively. Here, we report the draft genome sequence of the E. limosum ATCC 8486 (4.37 Mb) strain and its annotation information, including syngas fermentation and denitrification metabolic pathways.
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Pereira-Caro G, Borges G, Ky I, Ribas A, Calani L, Del Rio D, Clifford MN, Roberts SA, Crozier A. In vitro colonic catabolism of orange juice (poly)phenols. Mol Nutr Food Res 2015; 59:465-75. [DOI: 10.1002/mnfr.201400779] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 12/11/2014] [Accepted: 12/16/2014] [Indexed: 12/20/2022]
Affiliation(s)
- Gema Pereira-Caro
- Department of Technology; Postharvest and Food Industry; IFAPA-Alameda del Obispo; Córdoba Spain
| | - Gina Borges
- Department of Nutrition; University of California; Davis CA USA
| | - Isabelle Ky
- Institut des Sciences de la Vigne et du Vin; Université Bordeaux Segalen; Villenave d'Ornon Cedex France
| | - Aleix Ribas
- Bioquímica i Biotecnologia; Universitat Rovira i Virgili; Tarragona Spain
| | - Luca Calani
- Department of Food Science; University of Parma; Parma Italy
| | - Daniele Del Rio
- Department of Food Science; University of Parma; Parma Italy
| | - Michael N. Clifford
- Department of Nutritional Sciences; University of Surrey; Guildford Surrey UK
| | - Susan A. Roberts
- Global Scientific and Regulatory Affairs; The Coca-Cola Company; Atlanta GA USA
| | - Alan Crozier
- Department of Nutrition; University of California; Davis CA USA
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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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Zhang Y, Yang DH, Zhang YT, Chen XM, Li LL, Cai SQ. Biotransformation on the flavonolignan constituents of Silybi Fructus by an intestinal bacterial strain Eubacterium limosum ZL-II. Fitoterapia 2014; 92:61-71. [PMID: 24125915 DOI: 10.1016/j.fitote.2013.10.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Revised: 10/02/2013] [Accepted: 10/05/2013] [Indexed: 11/23/2022]
Abstract
Eubacterium limosum ZL-II is an anaerobic bacterium with demethylated activity, which was isolated from human intestinal bacteria in our previous work. In this study, the flavonolignan constituents of Silybi Fructus were biotransformed by E. limosum(1) ZL-II, producing four new transformation products - demethylisosilybin B (T1), demethylisosilybin A (T2), demethylsilybin B (T3) and demethylsilybin A (T4), among which T1 and T2 were new compounds. Their chemical structures were identified by ESI-TOF/MS, (1)H NMR, (13)C NMR, HMBC and CD spectroscopic data. The bioassay results showed that the transformation products T1-T4 exhibited significant inhibitory activities on Alzheimer's amyloid-β 42 (Aβ42(2)) aggregation with IC50 values at 7.49 μM-10.46 μM, which were comparable with that of the positive control (epigallocatechin gallate, EGCG(3), at 9.01 μM) and much lower than those of their parent compounds (at not less than 145.10 μM). The method of biotransformation by E. limosum ZL-II explored a way to develop the new and active lead compounds in Alzheimer's disease from Silybi Fructus. However, the transformation products T1-T4 exhibited decreased inhibitory activities against human tumor cell lines comparing with their parent compounds.
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Affiliation(s)
- Ying Zhang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Dong-Hui Yang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Ying-Tao Zhang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Xiu-Min Chen
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Li-Li Li
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Shao-Qing Cai
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
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Wang S, Gong T, Lu J, Kano Y, Yuan D. Simultaneous determination of tectorigenin and its metabolites in rat plasma by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2013; 933:50-8. [DOI: 10.1016/j.jchromb.2013.06.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Revised: 06/02/2013] [Accepted: 06/07/2013] [Indexed: 11/30/2022]
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Uehara M. Isoflavone metabolism and bone-sparing effects of daidzein-metabolites. J Clin Biochem Nutr 2013; 52:193-201. [PMID: 23704808 PMCID: PMC3652301 DOI: 10.3164/jcbn.13-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2013] [Accepted: 02/21/2013] [Indexed: 12/20/2022] Open
Abstract
Several dietary phytochemicals exhibit anti-oxidative, anti-inflammatory and anti-osteoporotic activities relevant to prevention of chronic diseases, including lifestyle-related diseases. Soybean isoflavones are similar in structure to estrogen and have received considerable attention as potential alternatives to hormone replacement therapy. Daidzein, a major isoflavone found in soybean, is metabolized to equol by intestinal microflora; this metabolite exhibits stronger estrogenic activity than daidzein. Recent studies suggest that the clinical effectiveness of isoflavones might be due to their ability to produce equol in the gut. This review focused on the metabolic pathway of equol and possible bioactivities of equol and O-desmethylangolensin, another metabolite of daidzein, with regard to bone metabolism and the status of intestinal microflora. Furthermore, we considered risk-benefit analyses of isoflavones and their metabolites.
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Affiliation(s)
- Mariko Uehara
- Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku. Tokyo 156-8502, Japan
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Shajib MTI, Pedersen HA, Mortensen AG, Kudsk P, Fomsgaard IS. Phytotoxic effect, uptake, and transformation of biochanin A in selected weed species. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:10715-10722. [PMID: 23030687 DOI: 10.1021/jf3023589] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Certain isoflavones are plant growth inhibitors, and biochanin A is a major isoflavone in clover species used for weed management. The effect of biochanin A on the monocot weed species Echinochloa crus-galli L. and Lolium perenne L. and dicot species Silene noctiflora L., Geranium molle L., and Amaranthus caudatus L. was evaluated in agar medium bioassays. S. noctiflora and G. molle root growth was progressively inhibited with increasing concentrations of biochanin A, whereas the monocot species were unaffected. With regard to the dicot species, S. noctiflora (EC(50) = 35.80 μM and EC(25) = 5.20 μM) was more susceptible than G. molle (EC(50), EC(25) > 400 μM). S. noctiflora, G. molle, and E. crus-galli root and shoot samples, representing a susceptible, a less susceptible, and a nonsusceptible species, respectively, were analyzed by LC-MS to quantify biochanin A and its transformation products. Biochanin A and its known transformation products genistein, dihydrobiochanin A, pratensein, and p-coumaric acid were quantified. Sissotrin was identified and quantified while assigning unknown peaks. The treated root samples contained more biochanin A, genistein, pratensein, and dihydrobiochanin A than shoot samples.
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Moco S, Martin FPJ, Rezzi S. Metabolomics view on gut microbiome modulation by polyphenol-rich foods. J Proteome Res 2012; 11:4781-90. [PMID: 22905879 DOI: 10.1021/pr300581s] [Citation(s) in RCA: 165] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Health is influenced by genetic, lifestyle, and diet determinants; therefore, nutrition plays an essential role in health management. Still, the substantiation of nutritional health benefits is challenged by the intrinsic macro- and micronutrient complexity of foods and individual responses. Evidence of healthy effects of food requires new strategies not only to stratify populations according to their metabolic requirements but also to predict and measure individual responses to dietary intakes. The influence of the gut microbiome and its interaction with the host is pivotal to understand nutrition and metabolism. Thus, the modulation of the gut microbiome composition by alteration of food habits has potentialities in health improvement or even disease prevention. Dietary polyphenols are naturally occurring constituents in vegetables and fruits, including coffee and cocoa. They are commonly associated to health benefits, although mechanistic evidence in vivo is not yet fully understood. Polyphenols are extensively metabolized by gut bacteria into a complex series of end-products that support a significant effect on the functional ecology of symbiotic partners that can affect the host physiology. This review reports recent nutritional metabolomics inspections of gut microbiota-host metabolic interactions with a particular focus on the cometabolism of cocoa and coffee polyphenols.
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Affiliation(s)
- Sofia Moco
- BioAnalytical Science, Nestle Research Center, Vers-chez-les-Blanc, PO Box 44, 1000 Lausanne 26, Switzerland.
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Rafii F, Sutherland JB, Bridges BM, Park M, Adams MR. Relationship of Dietary Soy Protein to Daidzein Metabolism by Cultures of Intestinal Microfloras from Monkeys. ACTA ACUST UNITED AC 2012. [DOI: 10.4236/fns.2012.32039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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50
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Colonic metabolites of berry polyphenols: the missing link to biological activity? Br J Nutr 2010; 104 Suppl 3:S48-66. [DOI: 10.1017/s0007114510003946] [Citation(s) in RCA: 312] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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