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Tian S, Chen M. Global research progress of gut microbiota and epigenetics: bibliometrics and visualized analysis. Front Immunol 2024; 15:1412640. [PMID: 38803501 PMCID: PMC11128553 DOI: 10.3389/fimmu.2024.1412640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/26/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND Gut microbiota is an important factor affecting host health. With the further study of the mechanism of gut microbiota, significant progress has been made in the study of the link between gut microbiota and epigenetics. This study visualizes the body of knowledge and research priorities between the gut microbiota and epigenetics through bibliometrics. METHODS Publications related to gut microbiota and epigenetics were searched in the Web of Science Core Collection (WoSCC) database. Vosviewer 1.6.17 and CiteSpace 6.1.R2 were used for bibliometric analysis. RESULTS WoSCC includes 460 articles from 71 countries. The number of publications on gut microbiota and epigenetics has increased each year since 2011. The USA, PEOPLES R CHINA, and ITALY are at the center of this field of research. The University of California System, Harvard University, and the University of London are the main research institutions. Li, X, Yu, Q, Zhang, S X are the top authors in this research field. We found that current research hotspots and frontiers include short-chain fatty acids (SCFA) play an important role in gut microbiota and epigenetic mechanisms, gut microbiota and epigenetics play an important role in host obesity, diet, and metabolism. Gut microbiota and epigenetics are closely related to colorectal cancer, breast cancer, and inflammatory bowel disease. At the same time, we found that gut microbiota regulates epigenetics through the gut-brain axis and has an impact on psychiatric diseases. Therefore, probiotics can regulate gut microbiota, improve lifestyle, and reduce the occurrence and development of diseases. CONCLUSION This is the first comprehensive and in-depth bibliometric study of trends and developments in the field of gut microbiota and epigenetics research. This study helps to guide the direction of research scholars in their current field of study.
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Affiliation(s)
- Siyu Tian
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine (TCM), Chengdu, China
| | - Min Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Potential Role of ROS in Butyrate- and Dietary Fiber-Mediated Growth Inhibition and Modulation of Cell Cycle-, Apoptosis- and Antioxidant-Relevant Proteins in LT97 Colon Adenoma and HT29 Colon Carcinoma Cells. Cancers (Basel) 2023; 15:cancers15020440. [PMID: 36672389 PMCID: PMC9857069 DOI: 10.3390/cancers15020440] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 12/28/2022] [Accepted: 01/06/2023] [Indexed: 01/12/2023] Open
Abstract
The aim of the present study was to examine whether reactive oxygen species (ROS) contribute to chemopreventive effects of fermentation supernatants (FS) of different dietary fibers (Synergy1®, oat-, barley-, yeast β-glucan, Curdlan) and butyrate as a fermentation metabolite. LT97 and HT29 cells were treated with butyrate and FS alone or with N-acetyl-cysteine (NAC) and their impact on ROS formation, cell growth, and protein expression (Cyclin D2, p21, PARP, Bid, GPx2) was investigated. Butyrate and FS significantly decreased cell growth. ROS levels were significantly increased, particularly in LT97 cells, while co-treatment with NAC decreased ROS formation and growth inhibitory effects in both cell lines. After treatment with butyrate and FS, Cyclin D2 expression was reduced in LT97 cells and p21 expression was increased in both cell lines. Levels of full-length PARP and Bid were decreased, while levels of cleaved PARP were enhanced. GPx2 expression was significantly reduced by fiber FS in HT29 cells. A notable effect of NAC on butyrate- and FS-modulated protein expression was observed exclusively for PARP and Bid in HT29 cells. From the present results, a contribution of ROS to growth inhibitory and apoptotic effects of butyrate and FS on LT97 and HT29 cells cannot be excluded.
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Asare PT, Lee CH, Hürlimann V, Teo Y, Cuénod A, Akduman N, Gekeler C, Afrizal A, Corthesy M, Kohout C, Thomas V, de Wouters T, Greub G, Clavel T, Pamer EG, Egli A, Maier L, Vonaesch P. A MALDI-TOF MS library for rapid identification of human commensal gut bacteria from the class Clostridia. Front Microbiol 2023; 14:1104707. [PMID: 36896425 PMCID: PMC9990839 DOI: 10.3389/fmicb.2023.1104707] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 01/31/2023] [Indexed: 02/25/2023] Open
Abstract
Introduction Microbial isolates from culture can be identified using 16S or whole-genome sequencing which generates substantial costs and requires time and expertise. Protein fingerprinting via Matrix-assisted Laser Desorption Ionization-time of flight mass spectrometry (MALDI-TOF MS) is widely used for rapid bacterial identification in routine diagnostics but shows a poor performance and resolution on commensal bacteria due to currently limited database entries. The aim of this study was to develop a MALDI-TOF MS plugin database (CLOSTRI-TOF) allowing for rapid identification of non-pathogenic human commensal gastrointestinal bacteria. Methods We constructed a database containing mass spectral profiles (MSP) from 142 bacterial strains representing 47 species and 21 genera within the class Clostridia. Each strain-specific MSP was constructed using >20 raw spectra measured on a microflex Biotyper system (Bruker-Daltonics) from two independent cultures. Results For validation, we used 58 sequence-confirmed strains and the CLOSTRI-TOF database successfully identified 98 and 93% of the strains, respectively, in two independent laboratories. Next, we applied the database to 326 isolates from stool of healthy Swiss volunteers and identified 264 (82%) of all isolates (compared to 170 (52.1%) with the Bruker-Daltonics library alone), thus classifying 60% of the formerly unknown isolates. Discussion We describe a new open-source MSP database for fast and accurate identification of the Clostridia class from the human gut microbiota. CLOSTRI-TOF expands the number of species which can be rapidly identified by MALDI-TOF MS.
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Affiliation(s)
- Paul Tetteh Asare
- Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.,Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland.,Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Chi-Hsien Lee
- Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.,Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Vera Hürlimann
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Youzheng Teo
- Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
| | - Aline Cuénod
- Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland.,Clinical Bacteriology and Mycology, University Hospital of Basel, Basel, Switzerland
| | - Nermin Akduman
- Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen, Tübingen, Germany.,Cluster of Excellence 'Controlling Microbes to Fight Infections', University of Tübingen, Tübingen, Germany
| | - Cordula Gekeler
- Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen, Tübingen, Germany.,Cluster of Excellence 'Controlling Microbes to Fight Infections', University of Tübingen, Tübingen, Germany
| | - Afrizal Afrizal
- Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany
| | - Myriam Corthesy
- Institute of Microbiology of the University of Lausanne, University Hospital Centre (CHUV), Lausanne, Switzerland
| | - Claire Kohout
- Duchossois Family Institute, Division of Infectious Diseases and Global Health, University of Chicago, Chicago, IL, United States
| | | | | | - Gilbert Greub
- Institute of Microbiology of the University of Lausanne, University Hospital Centre (CHUV), Lausanne, Switzerland
| | - Thomas Clavel
- Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany
| | - Eric G Pamer
- Duchossois Family Institute, Division of Infectious Diseases and Global Health, University of Chicago, Chicago, IL, United States
| | - Adrian Egli
- Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland.,Clinical Bacteriology and Mycology, University Hospital of Basel, Basel, Switzerland
| | - Lisa Maier
- Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen, Tübingen, Germany.,Cluster of Excellence 'Controlling Microbes to Fight Infections', University of Tübingen, Tübingen, Germany
| | - Pascale Vonaesch
- Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.,Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
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Ibrahim I, Syamala S, Ayariga JA, Xu J, Robertson BK, Meenakshisundaram S, Ajayi OS. Modulatory Effect of Gut Microbiota on the Gut-Brain, Gut-Bone Axes, and the Impact of Cannabinoids. Metabolites 2022; 12:1247. [PMID: 36557285 PMCID: PMC9781427 DOI: 10.3390/metabo12121247] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/30/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
The gut microbiome is a collection of microorganisms and parasites in the gastrointestinal tract. Many factors can affect this community's composition, such as age, sex, diet, medications, and environmental triggers. The relationship between the human host and the gut microbiota is crucial for the organism's survival and development, whereas the disruption of this relationship can lead to various inflammatory diseases. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are used to treat muscle spasticity associated with multiple sclerosis. It is now clear that these compounds also benefit patients with neuroinflammation. CBD and THC are used in the treatment of inflammation. The gut is a significant source of nutrients, including vitamins B and K, which are gut microbiota products. While these vitamins play a crucial role in brain and bone development and function, the influence of gut microbiota on the gut-brain and gut-bone axes extends further and continues to receive increasing scientific scrutiny. The gut microbiota has been demonstrated to be vital for optimal brain functions and stress suppression. Additionally, several studies have revealed the role of gut microbiota in developing and maintaining skeletal integrity and bone mineral density. It can also influence the development and maintenance of bone matrix. The presence of the gut microbiota can influence the actions of specific T regulatory cells, which can lead to the development of bone formation and proliferation. In addition, its metabolites can prevent bone loss. The gut microbiota can help maintain the bone's equilibrium and prevent the development of metabolic diseases, such as osteoporosis. In this review, the dual functions gut microbiota plays in regulating the gut-bone axis and gut-brain axis and the impact of CBD on these roles are discussed.
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Affiliation(s)
- Iddrisu Ibrahim
- The Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
| | - Soumyakrishnan Syamala
- Departments of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - Joseph Atia Ayariga
- The Industrial Hemp Program, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
| | - Junhuan Xu
- The Industrial Hemp Program, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
| | - Boakai K. Robertson
- The Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
| | - Sreepriya Meenakshisundaram
- Department of Microbiology and Biotechnology, JB Campus, Bangalore University, Bangalore 560 056, Karnataka, India
| | - Olufemi S. Ajayi
- The Industrial Hemp Program, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, AL 36104, USA
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Use of the β-Glucan-Producing Lactic Acid Bacteria Strains Levilactobacillus brevis and Pediococcus claussenii for Sourdough Fermentation-Chemical Characterization and Chemopreventive Potential of In Situ-Enriched Wheat and Rye Sourdoughs and Breads. Nutrients 2022; 14:nu14071510. [PMID: 35406123 PMCID: PMC9002695 DOI: 10.3390/nu14071510] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 03/31/2022] [Accepted: 04/02/2022] [Indexed: 12/17/2022] Open
Abstract
The aim of the present study was to examine β-glucan production and the potential prebiotic and chemopreventive effects of wheat and rye sourdoughs and breads generated with wild-type and non-β-glucan-forming isogenic mutant strains of Levilactobacillus brevis and Pediococcus claussenii. Sourdough and bread samples were subjected to in vitro digestion and fermentation. Fermentation supernatants (FS) and pellets (FP) were analyzed (pH values, short-chain fatty acids (SCFA), ammonia, bacterial taxa) and the effects of FS on LT97 colon adenoma cell growth, viability, caspase-2 and -3 activity, genotoxic and antigenotoxic effects and on gene and protein expression of p21, cyclin D2, catalase and superoxide dismutase 2 (SOD2) were examined. Concentrations of SCFA were increased and concentrations of ammonia were partly reduced in the FS. The relative abundance of Bifidobacteriaceae was increased in all FPs. Treatment with FS reduced the growth and viability of LT97 cells and significantly increased caspase-2 and -3 activities without exhibiting genotoxic or antigenotoxic effects. The p21 mRNA and protein levels were increased while that of cyclin D2 was reduced. Catalase and SOD2 mRNA and protein expression were marginally induced. The presented results indicate a comparable chemopreventive potential of wheat and rye sourdoughs and breads without an additional effect of the formed β-glucan.
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Oh S, Hosseindoust A, Ha S, Moturi J, Mun J, Tajudeen H, Kim J. Metabolic Responses of Dietary Fiber during Heat Stress: Effects on Reproductive Performance and Stress Level of Gestating Sows. Metabolites 2022; 12:metabo12040280. [PMID: 35448467 PMCID: PMC9028640 DOI: 10.3390/metabo12040280] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/10/2022] [Accepted: 03/19/2022] [Indexed: 02/07/2023] Open
Abstract
Heat stress is an important issue, and the addition of fiber to the diet is an option in modifying intestinal health. This study evaluated the effect of acid detergent fiber (ADF) levels on reproductive performance, intestinal integrity, and metabolism of gestating sows, and its carry-over effect on the lactation period during heat stress. The diets included 4.3% (Low fiber; LF), 5.4% (Medium fiber; MF), and 6.5% (High fiber; HF) ADF. Sows fed the HF diet showed a lower respiratory rate, hair cortisol concentration, and farrowing duration compared with the LF treatment. The HF diet increased the pyruvate, citrate cycle, glyoxylate, dicarboxylate, and thiamine metabolism compared with the MF. The concentration of acetate and total short-chain fatty acids were increased in the sows fed the HF diet. The gene expression of glucose transporter 3 and glucose transporter 4 was increased in the HF treatment. The gene expression of heat shock protein 70 was decreased in the HF treatment. The HF diet during gestation increased feed intake, constipation index, piglet weight, and litter weight compared with the LF. Sows in the LF treatment showed the greatest digestibility of crude protein and the lowest digestibility of ADF. In conclusion, a 6.5% ADF level is recommended for gestating sows during heat stress.
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Affiliation(s)
- SeungMin Oh
- Gyeongbuk Livestock Research Institute, Yeongju 63052, Korea;
| | - Abdolreza Hosseindoust
- Department of Animal Industry Convergence, Kangwon National University, Chuncheon 24341, Korea; (A.H.); (S.H.); (J.M.); (J.M.); (H.T.)
| | - SangHun Ha
- Department of Animal Industry Convergence, Kangwon National University, Chuncheon 24341, Korea; (A.H.); (S.H.); (J.M.); (J.M.); (H.T.)
| | - Joseph Moturi
- Department of Animal Industry Convergence, Kangwon National University, Chuncheon 24341, Korea; (A.H.); (S.H.); (J.M.); (J.M.); (H.T.)
| | - JunYoung Mun
- Department of Animal Industry Convergence, Kangwon National University, Chuncheon 24341, Korea; (A.H.); (S.H.); (J.M.); (J.M.); (H.T.)
| | - Habeeb Tajudeen
- Department of Animal Industry Convergence, Kangwon National University, Chuncheon 24341, Korea; (A.H.); (S.H.); (J.M.); (J.M.); (H.T.)
| | - JinSoo Kim
- Department of Animal Industry Convergence, Kangwon National University, Chuncheon 24341, Korea; (A.H.); (S.H.); (J.M.); (J.M.); (H.T.)
- Correspondence: ; Tel.: +82-33-250-8614
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7
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Yoo HY, Park SY, Chang SY, Kim SH. Regulation of Butyrate-Induced Resistance through AMPK Signaling Pathway in Human Colon Cancer Cells. Biomedicines 2021; 9:biomedicines9111604. [PMID: 34829834 PMCID: PMC8615665 DOI: 10.3390/biomedicines9111604] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/28/2021] [Accepted: 10/29/2021] [Indexed: 12/15/2022] Open
Abstract
Butyrates inhibit cell growth in colon cancer cells by inhibiting histone deacetylases. However, chronic exposure to butyrates induces butyrate resistance in colon cancer cells. The mechanism underlying the acquisition of resistance is not yet fully understood. Here, butyrate-resistant (BR) colon cancer cells were developed in HCT116, HT29, and SW480 human colon cancer cells and were confirmed by the increase in the inhibitory concentrations of cell growth by 50% (IC50) compared to their respective parental (PT) cells. Chronic exposure to butyrate induced autophagy via higher expression of Beclin-1 and LC3B-II. The AMP-activated protein kinase (AMPK) was downregulated along with the activation of Akt and mammalian target of rapamycin (mTOR) and decrease in acetyl-CoA carboxylase (ACC) in BR colon cancer cells compared to those in their respective PT cells. Activation of AMPK by AICAR treatment in BR colon cancer cells suppressed cell proliferation by inhibiting Akt and mTOR and activating ACC. Taken together, chronic exposure to butyrate increased butyrate resistance in human colon cancer by inducing protective autophagy through the downregulation of AMPK/ACC and activation of Akt/mTOR signaling. Activation of AMPK restored sensitivity to butyrate by the inhibition of Akt/mTOR, suggesting that AMPK could be a therapeutic target for BR colon cancers.
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Affiliation(s)
| | | | | | - So Hee Kim
- Correspondence: ; Tel.: +82-31-219-3451; Fax: +82-31-219-3435
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Schlörmann W, Bockwoldt JA, Mayr MF, Lorkowski S, Dawczynski C, Rohn S, Ehrmann MA, Glei M. Fermentation profile, cholesterol-reducing properties and chemopreventive potential of β-glucans from Levilactobacillus brevis and Pediococcus claussenii - a comparative study with β-glucans from different sources. Food Funct 2021; 12:10615-10631. [PMID: 34585204 DOI: 10.1039/d1fo02175c] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The aim of the present study was to investigate whether β-glucans obtained from the lactic acid bacteria (LAB) Levilactobacillus (L.) brevis and Pediococcus (P.) claussenii exhibit similar physiological effects such as cholesterol-binding capacity (CBC) as the structurally different β-glucans from oat, barley, and yeast as well as curdlan. After in vitro fermentation, fermentation supernatants (FSs) and/or -pellets (FPs) were analyzed regarding the concentrations of short-chain fatty acids (SCFAs), ammonia, bile acids, the relative abundance of bacterial taxa and chemopreventive effects (growth inhibition, apoptosis, genotoxicity) in LT97 colon adenoma cells. Compared to other glucans, the highest CBC was determined for oat β-glucan (65.9 ± 8.8 mg g-1, p < 0.05). Concentrations of SCFA were increased in FSs of all β-glucans (up to 2.7-fold). The lowest concentrations of ammonia (down to 0.8 ± 0.3 mmol L-1) and bile acids (2.5-5.2 μg mL-1) were detected in FSs of the β-glucans from oat, barley, yeast, and curdlan. The various β-glucans differentially modulated the relative abundance of bacteria families and reduced the Firmicutes/Bacteroidetes ratio. Treatment of LT97 cells with the FSs led to a significant dose-dependent growth reduction and increase in caspase-3 activity without exhibiting genotoxic effects. Though the different β-glucans show different fermentation profiles as well as cholesterol- and bile acid-reducing properties, they exhibit comparable chemopreventive effects.
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Affiliation(s)
- W Schlörmann
- Friedrich Schiller University Jena, Institute of Nutritional Sciences, Department of Applied Nutritional Toxicology, Dornburger Straße 24, 07743 Jena, Germany. .,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
| | - J A Bockwoldt
- Technical University of Munich, Chair of Technical Microbiology, Gregor-Mendel-Straße 4, 85354 Freising, Germany
| | - M F Mayr
- Friedrich Schiller University Jena, Institute of Nutritional Sciences, Department of Applied Nutritional Toxicology, Dornburger Straße 24, 07743 Jena, Germany.
| | - S Lorkowski
- Friedrich Schiller University Jena, Institute of Nutritional Sciences, Department of Nutritional Biochemistry and Physiology, Dornburger Straße 25, 07743 Jena, Germany.,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
| | - C Dawczynski
- Friedrich Schiller University Jena, Institute of Nutritional Sciences, Junior Research Group Nutritional Concepts, Dornburger Straße 29, 07743 Jena, Germany.,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
| | - S Rohn
- Technische Universität Berlin, Institute of Food Technology and Food Chemistry, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
| | - M A Ehrmann
- Technical University of Munich, Chair of Technical Microbiology, Gregor-Mendel-Straße 4, 85354 Freising, Germany
| | - M Glei
- Friedrich Schiller University Jena, Institute of Nutritional Sciences, Department of Applied Nutritional Toxicology, Dornburger Straße 24, 07743 Jena, Germany. .,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
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9
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Cytotoxic effects of butyric acid derivatives through GPR109A receptor in Colorectal Carcinoma cells by in silico and in vitro methods. J Mol Struct 2021. [DOI: 10.1016/j.molstruc.2021.130832] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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10
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Chen Y, Chen YX. Microbiota-Associated Metabolites and Related Immunoregulation in Colorectal Cancer. Cancers (Basel) 2021; 13:4054. [PMID: 34439208 PMCID: PMC8394439 DOI: 10.3390/cancers13164054] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/25/2021] [Accepted: 07/02/2021] [Indexed: 12/19/2022] Open
Abstract
A growing body of research has found close links between the human gut microbiota and colorectal cancer (CRC), associated with the direct actions of specific bacteria and the activities of microbiota-derived metabolites, which are implicated in complex immune responses, thus influencing carcinogenesis. Diet has a significant impact on the structure of the microbiota and also undergoes microbial metabolism. Some metabolites, such as short-chain fatty acids (SCFAs) and indole derivatives, act as protectors against cancer by regulating immune responses, while others may promote cancer. However, the specific influence of these metabolites on the host is conditional. We reviewed the recent insights on the relationships among diet, microbiota-derived metabolites, and CRC, focusing on their intricate immunomodulatory responses, which might influence the progression of colorectal cancer.
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Affiliation(s)
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200001, China;
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11
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do Prado SBR, Minguzzi BT, Hoffmann C, Fabi JP. Modulation of human gut microbiota by dietary fibers from unripe and ripe papayas: Distinct polysaccharide degradation using a colonic in vitro fermentation model. Food Chem 2021; 348:129071. [PMID: 33493843 DOI: 10.1016/j.foodchem.2021.129071] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 12/12/2020] [Accepted: 01/06/2021] [Indexed: 01/01/2023]
Abstract
Dietary fibers (DFs) consumption promotes a healthier gut through colonic fermentation and the modulation of different types of gut bacteria. The aim of this study is to evaluate the production of short-chain fatty acids (SCFA), metabolization of polysaccharides, and changes in the bacterial profile related to DFs extracted from the pulp of unripe and ripe papayas, using a batch colonic in vitro fermentation model. Our results show that fermentation of DFs from papayas induce the production of SCFAs and are utilized in different ways by intestinal microbiota. DFs from ripe papayas showed faster degradation by human gut microorganisms due to higher level of water-soluble polysaccharides. The fermentation of unripe papaya fibers increased the abundance of microorganisms belonging to family Clostridiaceae and genera Coprobacillus, Bulleidia, and Slackia, whereas both fibers increased Clostridium and Bacteroides, showing fruit ripeness affects the fermentation pattern of fruit fibers and their probable beneficial health aspects.
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Affiliation(s)
- Samira Bernardino Ramos do Prado
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Beatriz Toledo Minguzzi
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Christian Hoffmann
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; Food Research Center (FoRC), CEPID-FAPESP (Research, Innovation and Dissemination Centers, São Paulo Research Foundation), São Paulo, SP, Brazil
| | - João Paulo Fabi
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo, SP, Brazil; Food Research Center (FoRC), CEPID-FAPESP (Research, Innovation and Dissemination Centers, São Paulo Research Foundation), São Paulo, SP, Brazil.
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12
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Molina Ortiz JP, McClure DD, Shanahan ER, Dehghani F, Holmes AJ, Read MN. Enabling rational gut microbiome manipulations by understanding gut ecology through experimentally-evidenced in silico models. Gut Microbes 2021; 13:1965698. [PMID: 34455914 PMCID: PMC8432618 DOI: 10.1080/19490976.2021.1965698] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 07/01/2021] [Accepted: 07/27/2021] [Indexed: 02/04/2023] Open
Abstract
The gut microbiome has emerged as a contributing factor in non-communicable disease, rendering it a target of health-promoting interventions. Yet current understanding of the host-microbiome dynamic is insufficient to predict the variation in intervention outcomes across individuals. We explore the mechanisms that underpin the gut bacterial ecosystem and highlight how a more complete understanding of this ecology will enable improved intervention outcomes. This ecology varies within the gut over space and time. Interventions disrupt these processes, with cascading consequences throughout the ecosystem. In vivo studies cannot isolate and probe these processes at the required spatiotemporal resolutions, and in vitro studies lack the representative complexity required. However, we highlight that, together, both approaches can inform in silico models that integrate cellular-level dynamics, can extrapolate to explain bacterial community outcomes, permit experimentation and observation over ecological processes at high spatiotemporal resolution, and can serve as predictive platforms on which to prototype interventions. Thus, it is a concerted integration of these techniques that will enable rational targeted manipulations of the gut ecosystem.
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Affiliation(s)
- Juan P. Molina Ortiz
- School of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, Australia
- Faculty of Engineering, Centre for Advanced Food Engineering, The University of Sydney, Sydney, Australia
| | - Dale D. McClure
- School of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, Australia
- Faculty of Engineering, Centre for Advanced Food Engineering, The University of Sydney, Sydney, Australia
| | - Erin R. Shanahan
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, Australia
- Charles Perkins Centre, The University of Sydney, Sydney, Australia
| | - Fariba Dehghani
- School of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, Australia
- Faculty of Engineering, Centre for Advanced Food Engineering, The University of Sydney, Sydney, Australia
| | - Andrew J. Holmes
- Faculty of Engineering, Centre for Advanced Food Engineering, The University of Sydney, Sydney, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, Australia
- Charles Perkins Centre, The University of Sydney, Sydney, Australia
| | - Mark N. Read
- Faculty of Engineering, Centre for Advanced Food Engineering, The University of Sydney, Sydney, Australia
- Charles Perkins Centre, The University of Sydney, Sydney, Australia
- School of Computer Science, Faculty of Engineering, The University of Sydney, Sydney, Australia
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13
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Schlörmann W, Atanasov J, Lorkowski S, Dawczynski C, Glei M. Thermal Processing has no Impact on Chemopreventive Effects of Oat and Barley Kernels in LT97 Colon Adenoma Cells. Nutr Cancer 2020; 73:2708-2719. [PMID: 33305613 DOI: 10.1080/01635581.2020.1856892] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
The unique dietary fiber composition with high contents of β-glucan contributes to the health-promoting properties of oat and barley and may mediate a reduction of colon cancer risk. In the present study, chemopreventive effects of oat and barley (beta®barley) kernels were investigated. In order to address the impact of thermal processing on these effects, kernels were roasted (150-180 °C, approx. 20 min), digested and fermented using an In Vitro human digestion model. Concentrations of short-chain fatty acids (SCFA) and ammonia were determined in fermentation supernatants (FS). Growth inhibition, apoptosis, DNA integrity and gene expression of catalase were analyzed in LT97 colon adenoma cells. Concentrations of SCFA, particularly butyrate, were higher in oat/barley FS (2.2-fold, on average), while ammonia levels were significantly lower (0.7-fold, on average) than in the fermentation control. Treatment of LT97 cells with FS of oat/barley kernels led to a significant time- and dose-dependent growth reduction, a significant increase in caspase-3 activity and enhanced levels of catalase mRNA, without exhibiting genotoxic effects. In general, the results indicate a chemopreventive potential of In Vitro fermented oat and waxy winter barley mediated mainly by growth inhibitory and apoptotic effects, which are preserved after thermal processing.
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Affiliation(s)
- Wiebke Schlörmann
- Department of Nutritional Toxicology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.,Competence Cluster for Nutrition, Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
| | - Julia Atanasov
- Department of Nutritional Toxicology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
| | - Stefan Lorkowski
- Competence Cluster for Nutrition, Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany.,Department of Nutritional Biochemistry and Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
| | - Christine Dawczynski
- Competence Cluster for Nutrition, Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany.,Junior Research Group Nutritional Concepts, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
| | - Michael Glei
- Department of Nutritional Toxicology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.,Competence Cluster for Nutrition, Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
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14
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Impact of processing degree on fermentation profile and chemopreventive effects of oat and waxy barley in LT97 colon adenoma cells. Eur Food Res Technol 2020. [DOI: 10.1007/s00217-020-03645-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AbstractThe chemopreventive effects of β-glucan-rich cereals such as oat and barley (beta®barley) have been examined previously, but studies comparing fermentation characteristics and chemopreventive effects of oat and barley of different processing stages are rare. Therefore, the present study aims at investigating the fermentation end points (pH values, concentrations of short-chain fatty acids (SCFA) and ammonia) in fermentation supernatants (FS) obtained from differently processed oat and barley samples (kernels, thick and thin flakes). Chemopreventive effects of FS, such as growth inhibition, apoptosis, and induction of cell cycle- and redox-relevant genes (p21, SOD2), were analysed in LT97 colon adenoma cells. After fermentation, pH values were reduced (∆ pH − 1.3, on average) and SCFA concentrations were increased (∆ + 59 mmol/L, on average) with a shift towards butyrate formation in FS obtained from oat and barley samples compared to the fermentation negative control (FS blank). Ammonia was reduced more effectively in FS obtained from barley (∆ − 4.6 mmol/L, on average) than from oat samples (∆ − 1.0 mmol/L, on average). Treatment of LT97 cells with FS resulted in a time- and dose-dependent reduction of cell number, an increase in caspase-3 activity (up to 9.0-fold after 24 h, on average) and an induction of p21 (2.1-fold, on average) and SOD2 (2.3-fold, on average) mRNA expression, while no genotoxic effects were observed. In general, the results indicate no concrete effect of the type of cereal or processing stage on fermentation and chemopreventive effects of oat and barley.
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15
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Ocvirk S, Wilson AS, Posma JM, Li JV, Koller KR, Day GM, Flanagan CA, Otto JE, Sacco PE, Sacco FD, Sapp FR, Wilson AS, Newton K, Brouard F, DeLany JP, Behnning M, Appolonia CN, Soni D, Bhatti F, Methé B, Fitch A, Morris A, Gaskins HR, Kinross J, Nicholson JK, Thomas TK, O'Keefe SJD. A prospective cohort analysis of gut microbial co-metabolism in Alaska Native and rural African people at high and low risk of colorectal cancer. Am J Clin Nutr 2020; 111:406-419. [PMID: 31851298 PMCID: PMC6997097 DOI: 10.1093/ajcn/nqz301] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 11/14/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Alaska Native (AN) people have the world's highest recorded incidence of sporadic colorectal cancer (CRC) (∼91:100,000), whereas rural African (RA) people have the lowest risk (<5:100,000). Previous data supported the hypothesis that diet affected CRC risk through its effects on the colonic microbiota that produce tumor-suppressive or -promoting metabolites. OBJECTIVES We investigated whether differences in these metabolites may contribute to the high risk of CRC in AN people. METHODS A cross-sectional observational study assessed dietary intake from 32 AN and 21 RA healthy middle-aged volunteers before screening colonoscopy. Analysis of fecal microbiota composition by 16S ribosomal RNA gene sequencing and fecal/urinary metabolites by 1H-NMR spectroscopy was complemented with targeted quantification of fecal SCFAs, bile acids, and functional microbial genes. RESULTS Adenomatous polyps were detected in 16 of 32 AN participants, but not found in RA participants. The AN diet contained higher proportions of fat and animal protein and less fiber. AN fecal microbiota showed a compositional predominance of Blautia and Lachnoclostridium, higher microbial capacity for bile acid conversion, and low abundance of some species involved in saccharolytic fermentation (e.g., Prevotellaceae, Ruminococcaceae), but no significant lack of butyrogenic bacteria. Significantly lower concentrations of tumor-suppressive butyrate (22.5 ± 3.1 compared with 47.2 ± 7.3 SEM µmol/g) coincided with significantly higher concentrations of tumor-promoting deoxycholic acid (26.7 ± 4.2 compared with 11 ± 1.9 µmol/g) in AN fecal samples. AN participants had lower quantities of fecal/urinary metabolites than RA participants and metabolite profiles correlated with the abundance of distinct microbial genera in feces. The main microbial and metabolic CRC-associated markers were not significantly altered in AN participants with adenomatous polyps. CONCLUSIONS The low-fiber, high-fat diet of AN people and exposure to carcinogens derived from diet or environment are associated with a tumor-promoting colonic milieu as reflected by the high rates of adenomatous polyps in AN participants.
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Affiliation(s)
- Soeren Ocvirk
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Annette S Wilson
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Joram M Posma
- Section of Bioinformatics, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, London, United Kingdom
| | - Jia V Li
- Section of Nutritional Research, Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Imperial College, London, United Kingdom
- Centre for Digestive and Gut Health, Institution of Global Health Innovation, Imperial College, London, United Kingdom
| | - Kathryn R Koller
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Gretchen M Day
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Christie A Flanagan
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Jill Evon Otto
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Pam E Sacco
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Frank D Sacco
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Flora R Sapp
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Amy S Wilson
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Keith Newton
- Division of Gastroenterology, University of KwaZulu-Natal, Durban, South Africa
| | - Faye Brouard
- Manguzi Hospital, Manguzi, KwaZulu-Natal, South Africa
| | - James P DeLany
- Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Translational Research Institute for Metabolism and Diabetes, Advent Health, Orlando, FL, USA
| | - Marissa Behnning
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Corynn N Appolonia
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Devavrata Soni
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Faheem Bhatti
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Barbara Methé
- Center for Medicine and the Microbiome, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Adam Fitch
- Center for Medicine and the Microbiome, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Alison Morris
- Center for Medicine and the Microbiome, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - H Rex Gaskins
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - James Kinross
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, United Kingdom
| | - Jeremy K Nicholson
- Centre for Digestive and Gut Health, Institution of Global Health Innovation, Imperial College, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, United Kingdom
| | - Timothy K Thomas
- Clinical & Research Services, Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Stephen J D O'Keefe
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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16
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Schlörmann W, Atanasov J, Lorkowski S, Dawczynski C, Glei M. Study on chemopreventive effects of raw and roasted β-glucan-rich waxy winter barley using an in vitro human colon digestion model. Food Funct 2020; 11:2626-2638. [DOI: 10.1039/c9fo03009c] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Fermentation supernatants of barley flakes exhibit chemopreventive effects in LT97 colon adenoma cells without impact of roasting.
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Affiliation(s)
- W. Schlörmann
- Friedrich Schiller University Jena
- Institute of Nutritional Sciences
- Department of Nutritional Toxicology
- 07743 Jena
- Germany
| | - J. Atanasov
- Friedrich Schiller University Jena
- Institute of Nutritional Sciences
- Department of Nutritional Toxicology
- 07743 Jena
- Germany
| | - S. Lorkowski
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD)
- Halle-Jena-Leipzig
- Germany
- Friedrich Schiller University Jena
- Institute of Nutritional Sciences
| | - C. Dawczynski
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD)
- Halle-Jena-Leipzig
- Germany
- Friedrich Schiller University Jena
- Institute of Nutritional Sciences
| | - M. Glei
- Friedrich Schiller University Jena
- Institute of Nutritional Sciences
- Department of Nutritional Toxicology
- 07743 Jena
- Germany
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17
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Royston KJ, Adedokun B, Olopade OI. Race, the microbiome and colorectal cancer. World J Gastrointest Oncol 2019; 11:773-787. [PMID: 31662819 PMCID: PMC6815924 DOI: 10.4251/wjgo.v11.i10.773] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 07/17/2019] [Accepted: 07/26/2019] [Indexed: 02/05/2023] Open
Abstract
In the past decade, more cancer researchers have begun to understand the significance of cancer prevention, which has prompted a shift in the increasing body of scientific literature. An area of fascination and great potential is the human microbiome. Recent studies suggest that the gut microbiota has significant roles in an individual's ability to avoid cancer, with considerable focus on the gut microbiome and colorectal cancer. That in mind, racial disparities with regard to colorectal cancer treatment and prevention are generally understudied despite higher incidence and mortality rates among Non-Hispanic Blacks compared to other racial and ethnic groups in the United States. A comprehension of ethnic differences with relation to colorectal cancer, dietary habits and the microbiome is a meritorious area of investigation. This review highlights literature that identifies and bridges the gap in understanding the role of the human microbiome in racial disparities across colorectal cancer. Herein, we explore the differences in the gut microbiota, common short chain fatty acids produced in abundance by microbes, and their association with racial differences in cancer acquisition.
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Affiliation(s)
- Kendra J Royston
- Division of Hematology Oncology, University of Chicago, Chicago, IL 60637, United States
| | - Babatunde Adedokun
- Center for Clinical Cancer Genetics and Global Health Department of Medicine, University of Chicago, Chicago, IL 60637, United States
| | - Olufunmilayo I Olopade
- Division of Hematology Oncology, University of Chicago, Chicago, IL 60637, United States
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18
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O'Keefe SJD. Plant-based foods and the microbiome in the preservation of health and prevention of disease. Am J Clin Nutr 2019; 110:265-266. [PMID: 31268135 PMCID: PMC6669048 DOI: 10.1093/ajcn/nqz127] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Affiliation(s)
- Stephen J D O'Keefe
- Division of Gastroenterology, University of Pittsburgh, Pittsburgh, PA, USA,African Microbiome Institute, University of Stellenbosch, Stellenbosch, South Africa,Address correspondence to SJDO (e-mail: )
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19
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Jiang X, Lu N, Xue Y, Liu S, Lei H, Tu W, Lu Y, Xia D. Crude fiber modulates the fecal microbiome and steroid hormones in pregnant Meishan sows. Gen Comp Endocrinol 2019; 277:141-147. [PMID: 30951727 DOI: 10.1016/j.ygcen.2019.04.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 03/11/2019] [Accepted: 04/01/2019] [Indexed: 01/22/2023]
Abstract
The beneficial effects of dietary fiber on the reproductive performance and welfare of sows have been discussed broadly, but few researches examined the causal changes and the association of gut microbiota and the steroid hormones, the main regulators of reproductive function. To shed light on this, thirty-six Meishan sows were allocated into 2.5% crude fiber (CF) group and 7.5% CF group respectively for an entire farrowing interval. On the 90th day of gestation, the saliva and fresh stool of sows were individually collected in the morning (06:00-07:00) for steroid hormones, short-chain fatty acids (SCFAs) and microbiome analysis. In addition, the parameter of pregnant behavioral and farrowing performance was recorded and evaluated. We observed that, as compared with the 2.5% CF treatment, 7.5% CF significantly increased the litter size (p = 0.01), reduced the stereotypic behaviors including sham chewing, rolling tongue and licking ground (p = 0.02, 0.04, 0.01) at later gestation stage, but increased lying time (p = 0.00). In coincide with this, 7.5% CF diet increased the salivary progesterone (p = 0.00), fecal estradiol and progesterone (p = 0.01, 0.02) level, fecal water and SCFAs content (p = 0.02, 0.03), decreased the salivary and fecal cortisol (p = 0.01, 0.00) level. Further, 7.5% CF diet increased the fecal microbiota richness (ACE, p = 0.04; Chao, p = 0.07) and diversity (Shannon, p = 0.01; Simpson, p = 0.04), the proportion of genus Ruminococcus, Butyrivibrio, Lactobacillus and Fibrobacter (p = 0.02, 0.05, 0.04, 0.00), whereas reduced the proportion of genus Clostridium, Streptococcus, Bacteroides and Escherichia-Shigella (p = 0.00, 0.00, 0.04, 0.04). These results indicate that, fibrous diet can regulate the steroid hormones secretion and modulate the gut with more cellulose-degrading and probiotic bacterium, but less opportunistic pathogens, and this may contribute to the improvement of reproductive performance and welfare in sows.
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Affiliation(s)
- Xueyuan Jiang
- Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences, Shanghai, PR China
| | - Naisheng Lu
- Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences, Shanghai, PR China
| | - Yun Xue
- Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences, Shanghai, PR China; Shanghai Animal Disease Control Center, Shanghai, PR China
| | - Suli Liu
- Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences, Shanghai, PR China
| | - Hulong Lei
- Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences, Shanghai, PR China
| | - Weilong Tu
- Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences, Shanghai, PR China
| | - Yang Lu
- Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences, Shanghai, PR China
| | - Dong Xia
- Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences, Shanghai, PR China.
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20
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Kumar M, Ji B, Babaei P, Das P, Lappa D, Ramakrishnan G, Fox TE, Haque R, Petri WA, Bäckhed F, Nielsen J. Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling. Metab Eng 2018; 49:128-142. [PMID: 30075203 PMCID: PMC6871511 DOI: 10.1016/j.ymben.2018.07.018] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 07/30/2018] [Accepted: 07/30/2018] [Indexed: 12/31/2022]
Abstract
Malnutrition is a severe non-communicable disease, which is prevalent in children from low-income countries. Recently, a number of metagenomics studies have illustrated associations between the altered gut microbiota and child malnutrition. However, these studies did not examine metabolic functions and interactions between individual species in the gut microbiota during health and malnutrition. Here, we applied genome-scale metabolic modeling to model the gut microbial species, which were selected from healthy and malnourished children from three countries. Our analysis showed reduced metabolite production capabilities in children from two low-income countries compared with a high-income country. Additionally, the models were also used to predict the community-level metabolic potentials of gut microbes and the patterns of pairwise interactions among species. Hereby we found that due to bacterial interactions there may be reduced production of certain amino acids in malnourished children compared with healthy children from the same communities. To gain insight into alterations in the metabolism of malnourished (stunted) children, we also performed targeted plasma metabolic profiling in the first 2 years of life of 25 healthy and 25 stunted children. Plasma metabolic profiling further revealed that stunted children had reduced plasma levels of essential amino acids compared to healthy controls. Our analyses provide a framework for future efforts towards further characterization of gut microbial metabolic capabilities and their contribution to malnutrition.
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Affiliation(s)
- Manish Kumar
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE41128 Gothenburg, Sweden
| | - Boyang Ji
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE41128 Gothenburg, Sweden
| | - Parizad Babaei
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE41128 Gothenburg, Sweden
| | - Promi Das
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE41128 Gothenburg, Sweden
| | - Dimitra Lappa
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE41128 Gothenburg, Sweden
| | - Girija Ramakrishnan
- Department of Medicine/Division of Infectious Diseases, and University of Virginia, Charlottesville, VA, USA
| | - Todd E Fox
- Department of Pharmacology, University of Virginia, Charlottesville, VA, USA
| | - Rashidul Haque
- International Centre for Diarrheal Disease Research, Dhaka, Bangladesh
| | - William A Petri
- Department of Medicine/Division of Infectious Diseases, and University of Virginia, Charlottesville, VA, USA
| | - Fredrik Bäckhed
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Jens Nielsen
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE41128 Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK2800 Lyngby, Denmark.
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21
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Yin DT, Fu Y, Zhao XH. In vitro activities of inulin fermentation products to HCT-116 cells enhanced by the cooperation between exogenous strains and adult faecal microbiota. Int J Food Sci Nutr 2018; 69:814-823. [PMID: 29318896 DOI: 10.1080/09637486.2017.1418844] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Inulin was fermented by adult faecal microbiota and 10 exogenous strains for 24 or 48 h. The contents of acetate, propionate, butyrate and lactate were quantified in the fermented products, and the growth-inhibitory and apoptosis-inducing effects on a human colon cell line (HCT-116 cells) were assessed. Most of these strains increased contents of acetate, propionate and butyrate, and promoted lactate conversion. Correlation analysis suggested that butyrate and lactate in the fermentation products were positively and negatively correlated with the measured inhibition ratios (p < .05). The results were mostly consistent with the verification trial results using standard acid solutions. The fermentation products could cause apoptosis via inducing DNA fragmentation and increasing total apoptotic populations in the treated cells. Moreover, the fermentation products with higher growth-inhibitory activities demonstrated the increased apoptosis-inducing properties. In conclusion, these strains could cooperate with adult faecal microbiota to confer inulin fermentation products with higher anti-colon cancer activity.
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Affiliation(s)
- Dan-Ting Yin
- a Key Laboratory of Dairy Science, Ministry of Education , Northeast Agricultural University , Harbin , People's Republic of China
| | - Yu Fu
- b Department of Food Science, Faculty of Science , University of Copenhagen , Frederiksberg C , Denmark
| | - Xin-Huai Zhao
- a Key Laboratory of Dairy Science, Ministry of Education , Northeast Agricultural University , Harbin , People's Republic of China.,c Department of Food Science , Northeast Agricultural University , Harbin , People's Republic of China
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22
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Xiao X, Cao Y, Chen H. Profiling and characterization of microRNAs responding to sodium butyrate treatment in A549 cells. J Cell Biochem 2018; 119:3563-3573. [PMID: 29231270 DOI: 10.1002/jcb.26547] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Accepted: 11/30/2017] [Indexed: 01/01/2023]
Abstract
Butyrate inhibits growth of lung cancer. However, the molecular mechanism is still unclear. Here we profiled miRNAs that responded to sodium butyrate(NaB) stimulation in A549 cells, a non-small cell lung cancer cell line, using microarray. We found 33 up-regulated microRNAs and 22 down-regulated microRNAs (log2 ≥1.5 folds, P-value <0.05). The expression of miR-3935, miR-574-3p, and miR-494-3p was confirmed by realtime qPCR. Then,we explored their potential targets of miR-3935 and miR-494-3p using long noncoding RNA(LncRNA) microarray. Using cell expressing negative microRNA as control, we found 103 up-regulated transcripts (including 69 mRNA and 34 LncRNA), and 36 down-regulated transcripts (including 34 mRNAs and 2 LncRNA), in miR-3935 over-expressing A549 cells; 128 up-regulated transcripts (121 mRNAs, 7 LncRNAs) and 180 down-regulated transcripts (169 mRNAs, 11 LncRNAs) in mir-494-3p, respectively (log2 Fold change ≥ 1 & P < 0.05). The expression of RNF115, NTRK3, SLC39A6, and USB1 was confirmed with qPCR. Immunoblotting was adopted to detect RNF115 expression in miR-3935 overexpressed A549 cells. Then, using a luciferase reporter assay system, we found that miR-3935 overexpression significantly decreased 3UTR of RNF115 mediated luciferase expression .In addition, we also observed that the proliferation and migration of A549 cells was obviously prevented by miR-3935 overexpression. Finally, we showed miR-3935 and miR-494-3p induced interferon stimulated gene 15(ISG15) expression through activating its promoter transcription. Together, we profiled microRNAs that responded to NaB treatment and characterized their biological functions in A549 cells. Those results provided new clue for the future treatment of non small cell lung cancer.
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Affiliation(s)
- Xiaoqiang Xiao
- Joint Shantou International Eye Center, Shantou University and the Chinese University of Hong Kong, Shantou, China
| | - Yingjie Cao
- Joint Shantou International Eye Center, Shantou University and the Chinese University of Hong Kong, Shantou, China
| | - Haoyu Chen
- Joint Shantou International Eye Center, Shantou University and the Chinese University of Hong Kong, Shantou, China
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Di Ciaula A, Wang DQH, Molina-Molina E, Lunardi Baccetto R, Calamita G, Palmieri VO, Portincasa P. Bile Acids and Cancer: Direct and Environmental-Dependent Effects. Ann Hepatol 2017; 16:s87-s105. [PMID: 29080344 DOI: 10.5604/01.3001.0010.5501] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Accepted: 09/06/2017] [Indexed: 02/05/2023]
Abstract
Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i.e. prostate, breast) through a complex series of mechanisms including direct oxidative stress with DNA damage, apoptosis, epigenetic factors regulating gene expression, reduced/increased expression of nuclear receptors (mainly farnesoid X receptor, FXR) and altered composition of gut microbiota, also acting as a common interface between environmental factors (including diet, lifestyle, exposure to toxics) and the molecular events promoting cancerogenesis. Primary prevention strategies (i.e. changes in dietary habits and lifestyle, reduced exposure to environmental toxics) mainly able to modulate gut microbiota and the epigenome, and the therapeutic use of hydrophilic BAs to counterbalance the negative effects of the more hydrophobic BAs might be, in the near future, part of useful tools for cancer prevention and management.
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Affiliation(s)
| | - David Q-H Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Emilio Molina-Molina
- Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy
| | - Raquel Lunardi Baccetto
- Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy
| | - Giuseppe Calamita
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari. Italy
| | - Vincenzo O Palmieri
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari. Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy
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Bile acids and colon cancer: Is FXR the solution of the conundrum? Mol Aspects Med 2017; 56:66-74. [DOI: 10.1016/j.mam.2017.04.002] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 03/20/2017] [Accepted: 04/07/2017] [Indexed: 02/07/2023]
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25
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Nurdin SU, Le Leu RK, Young GP, Stangoulis JCR, Christophersen CT, Abbott CA. Analysis of the Anti-Cancer Effects of Cincau Extract (Premna oblongifolia Merr) and Other Types of Non-Digestible Fibre Using Faecal Fermentation Supernatants and Caco-2 Cells as a Model of the Human Colon. Nutrients 2017; 9:nu9040355. [PMID: 28368356 PMCID: PMC5409694 DOI: 10.3390/nu9040355] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 03/16/2017] [Accepted: 03/29/2017] [Indexed: 02/04/2023] Open
Abstract
Green cincau (Premna oblongifolia Merr) is an Indonesian food plant with a high dietary fibre content. Research has shown that dietary fibre mixtures may be more beneficial for colorectal cancer prevention than a single dietary fibre type. The aim of this study was to investigate the effects of green cincau extract on short chain fatty acid (SCFA) production in anaerobic batch cultures inoculated with human faecal slurries and to compare these to results obtained using different dietary fibre types (pectin, inulin, and cellulose), singly and in combination. Furthermore, fermentation supernatants (FSs) were evaluated in Caco-2 cells for their effect on cell viability, differentiation, and apoptosis. Cincau increased total SCFA concentration by increasing acetate and propionate, but not butyrate concentration. FSs from all dietary fibre sources, including cincau, reduced Caco-2 cell viability. However, the effects of all FSs on cell viability, cell differentiation, and apoptosis were not simply explainable by their butyrate content. In conclusion, products of fermentation of cincau extracts induced cell death, but further work is required to understand the mechanism of action. This study demonstrates for the first time that this Indonesian traditional source of dietary fibre may be protective against colorectal cancer.
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Affiliation(s)
- Samsu U Nurdin
- School of Biological Sciences, Flinders University, Adelaide, SA 5042, Australia.
- Department of Agricultural Product Technology, Lampung University, Bandar Lampung 35145, Indonesia.
- Flinders Centre for Innovation in Cancer, Adelaide, SA 5042, Australia.
| | - Richard K Le Leu
- Flinders Centre for Innovation in Cancer, Adelaide, SA 5042, Australia.
- CSIRO Food and Nutrition, Adelaide, SA 5000, Australia.
| | - Graeme P Young
- Flinders Centre for Innovation in Cancer, Adelaide, SA 5042, Australia.
| | - James C R Stangoulis
- School of Biological Sciences, Flinders University, Adelaide, SA 5042, Australia.
| | - Claus T Christophersen
- CSIRO Food and Nutrition, Adelaide, SA 5000, Australia.
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.
| | - Catherine A Abbott
- School of Biological Sciences, Flinders University, Adelaide, SA 5042, Australia.
- Flinders Centre for Innovation in Cancer, Adelaide, SA 5042, Australia.
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26
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Abstract
Colorectal cancer is one of the so-called westernized diseases and the second leading cause of cancer death worldwide. On the basis of global epidemiological and scientific studies, evidence suggests that the risk of colorectal cancer is increased by processed and unprocessed meat consumption but suppressed by fibre, and that food composition affects colonic health and cancer risk via its effects on colonic microbial metabolism. The gut microbiota can ferment complex dietary residues that are resistant to digestion by enteric enzymes. This process provides energy for the microbiota but culminates in the release of short-chain fatty acids including butyrate, which are utilized for the metabolic needs of the colon and the body. Butyrate has a remarkable array of colonic health-promoting and antineoplastic properties: it is the preferred energy source for colonocytes, it maintains mucosal integrity and it suppresses inflammation and carcinogenesis through effects on immunity, gene expression and epigenetic modulation. Protein residues and fat-stimulated bile acids are also metabolized by the microbiota to inflammatory and/or carcinogenic metabolites, which increase the risk of neoplastic progression. This Review will discuss the mechanisms behind these microbial metabolite effects, which could be modified by diet to achieve the objective of preventing colorectal cancer in Western societies.
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27
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Hegedüs R, Pauschert A, Orbán E, Szabó I, Andreu D, Marquardt A, Mező G, Manea M. Modification of daunorubicin-GnRH-III bioconjugates with oligoethylene glycol derivatives to improve solubility and bioavailability for targeted cancer chemotherapy. Biopolymers 2016; 104:167-77. [PMID: 25753049 DOI: 10.1002/bip.22629] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Revised: 02/18/2015] [Accepted: 02/24/2015] [Indexed: 12/16/2022]
Abstract
Daunorubicin-GnRH-III bioconjugates have recently been developed as drug delivery systems with potential applications in targeted cancer chemotherapy. In order to improve their biochemical properties, several strategies have been pursued: (1) incorporation of an enzymatic cleavable spacer between the anticancer drug and the peptide-based targeting moiety, (2) peptide modification by short chain fatty acids, or (3) attachment of two anticancer drugs to the same GnRH-III derivative. Although these modifications led to more potent bioconjugates, a decrease in their solubility was observed. Here we report on the design, synthesis and biochemical characterization of daunorubicin-GnRH-III bioconjugates with increased solubility, which could be achieved by incorporating oligoethylene glycol-based spacers in their structure. First, we have evaluated the effect of an oligoethylene glycol-based spacer on the solubility, enzymatic stability/degradation, cellular uptake, and in vitro cytostatic effect of a bioconjugate containing only one daunorubicin attached through a GFLG tetrapeptide spacer to the GnRH-III targeting moiety. Thereafter, more complex compounds containing two copies of daunorubicin, GFLG spacers as well as Lys(nBu) in position 4 of GnRH-III were synthesized and biochemically characterized. Our results indicated that all synthesized oligoethylene glycol-containing bioconjugates had higher solubility in cell culture medium than the unmodified analogs. They were degraded in the presence of rat liver lysosomal homogenate leading to the formation of small drug containing metabolites. In the case of bioconjugates containing two copies of daunorubicin, the incorporation of oligoethylene glycol-based spacers led to increased in vitro cytostatic effect on MCF-7 human breast cancer cells.
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Affiliation(s)
- Rózsa Hegedüs
- MTA-ELTE Research Group of Peptide Chemistry, Eötvös L. University, 1117, Budapest, Hungary
| | - Aline Pauschert
- Department of Chemistry, University of Konstanz, 78457, Konstanz, Germany
| | - Erika Orbán
- MTA-ELTE Research Group of Peptide Chemistry, Eötvös L. University, 1117, Budapest, Hungary
| | - Ildikó Szabó
- MTA-ELTE Research Group of Peptide Chemistry, Eötvös L. University, 1117, Budapest, Hungary
| | - David Andreu
- Department of Experimental and Health Sciences, Pompeu Fabra University, 08003, Barcelona, Spain
| | - Andreas Marquardt
- Proteomics Facility, Department of Biology, University of Konstanz, 78457, Konstanz, Germany
| | - Gábor Mező
- MTA-ELTE Research Group of Peptide Chemistry, Eötvös L. University, 1117, Budapest, Hungary
| | - Marilena Manea
- Department of Chemistry, University of Konstanz, 78457, Konstanz, Germany.,Zukunftskolleg, University of Konstanz, 78457, Konstanz, Germany
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Myint H, Kishi H, Koike S, Kobayashi Y. Effect of chickpea husk dietary supplementation on blood and cecal parameters in rats. Anim Sci J 2016; 88:372-378. [PMID: 27328875 DOI: 10.1111/asj.12651] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Revised: 03/24/2016] [Accepted: 04/07/2016] [Indexed: 12/22/2022]
Abstract
Chickpea husk was functionally evaluated for antioxidant status, blood parameters, cecal fermentation and microbial profiles in rats. Fifteen male rats (5 weeks of age) were divided into three groups; they were individually housed and fed one of the following diets for 3 weeks: purified diet containing 5% cellulose (Cellulose), an identical diet in which cellulose was replaced by corn starch (Starch) or by chickpea husk (Chick). Rats were sacrificed to obtain blood and cecal digesta samples. Chickpea husk contained high polyphenolic content and significant superoxide dismutase and 2,2-diphenyl-picrylhydrazyl scavenging activities. In a feeding experiment, Chick showed lowered cholesterol levels and improved antioxidant activity represented by reduced thiobarbituric acid reactive substances in blood. Chick showed increased cecal levels of total short chain fatty acids and butyrate, leading to a lower pH. Chick presented with lowered cecal indole and skatole concentrations, as did Cellulose. Cecal bacterial changes were notable in Chick, evidenced by differences in denaturing gradient gel electrophoresis banding patterns. However, representative bacteria quantified by real-time PCR assay did not support this bacterial change. These results indicate that chickpea husk feeding can improve the antioxidative status of rats through its polyphenolic components and modulate the hindgut environment by its fibrous components.
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Affiliation(s)
- Htun Myint
- Graduate School of Agriculture, Hokkaido University, Kita, Sapporo, Japan
| | - Hiroyuki Kishi
- Graduate School of Agriculture, Hokkaido University, Kita, Sapporo, Japan
| | - Satoshi Koike
- Graduate School of Agriculture, Hokkaido University, Kita, Sapporo, Japan
| | - Yasuo Kobayashi
- Graduate School of Agriculture, Hokkaido University, Kita, Sapporo, Japan
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Kapuvári B, Hegedüs R, Schulcz Á, Manea M, Tóvári J, Gacs A, Vincze B, Mező G. Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice. Invest New Drugs 2016; 34:416-23. [PMID: 27146514 PMCID: PMC4919375 DOI: 10.1007/s10637-016-0354-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 04/12/2016] [Indexed: 12/01/2022]
Abstract
Compared to classical chemotherapy, peptide-based drug targeting is a promising therapeutic approach for cancer, which can provide increased selectivity and decreased side effects to anticancer drugs. Among various homing devices, gonadotropin-releasing hormone-III (GnRH-III) peptide represents a suitable targeting moiety, in particular in the treatment of hormone independent tumors that highly express GnRH receptors (e.g. colon carcinoma). We have previously shown that GnRH-III[4Lys(Ac),8Lys(Dau = Aoa)] bioconjugate, in which daunorubicin was attached via oxime linkage to the 8Lys of a GnRH-III derivative, exerted significant in vivo antitumor effect on subcutaneously developed HT-29 colon tumor. In contrast, results of the study reported here indicated that this compound was not active on an orthotopically developed tumor. However, if Lys in position 4 was acylated with butyric acid instead of acetic acid, the resulting bioconjugate GnRH-III[4Lys(Bu),8Lys(Dau = Aoa)] had significant tumor growth inhibitory effect. Furthermore, it prevented tumor neovascularization, without detectable side effects. Nevertheless, the development of metastases could not be inhibited by the bioconjugate; therefore, its application in combination with a metastasis preventive agent might be necessary in order to achieve complete tumor remission. In spite of this result, the treatment with GnRH-III[4Lys(Bu),8Lys(Dau = Aoa)] bioconjugate proved to have significant benefits over the administration of free daunorubicin, which was used at the maximum tolerated dose.
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Affiliation(s)
| | - Rózsa Hegedüs
- MTA-ELTE, Research Group of Peptide Chemistry, Pázmány P. stny. 1/A, Budapest, 1117, Hungary
| | - Ákos Schulcz
- National Institute of Oncology, Budapest, 1122, Hungary
| | - Marilena Manea
- Department of Chemistry and Zukunftskolleg, University of Konstanz, 78457, Constance, Germany
| | - József Tóvári
- National Institute of Oncology, Budapest, 1122, Hungary
| | | | | | - Gábor Mező
- MTA-ELTE, Research Group of Peptide Chemistry, Pázmány P. stny. 1/A, Budapest, 1117, Hungary.
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Peukert M, Thiel J, Mock HP, Marko D, Weschke W, Matros A. Spatiotemporal Dynamics of Oligofructan Metabolism and Suggested Functions in Developing Cereal Grains. FRONTIERS IN PLANT SCIENCE 2016; 6:1245. [PMID: 26834760 PMCID: PMC4717867 DOI: 10.3389/fpls.2015.01245] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Accepted: 12/21/2015] [Indexed: 05/21/2023]
Abstract
Oligofructans represent one of the most important groups of sucrose-derived water-soluble carbohydrates in the plant kingdom. In cereals, oligofructans accumulate in above ground parts of the plants (stems, leaves, seeds) and their biosynthesis leads to the formation of both types of glycosidic linkages [β(2,1); β(2,6)-fructans] or mixed patterns. In recent studies, tissue- and development- specific distribution patterns of the various oligofructan types in cereal grains have been shown, which are possibly related to the different phases of grain development, such as cellular differentiation of grain tissues and storage product accumulation. Here, we summarize the current knowledge about oligofructan biosynthesis and accumulation kinetics in cereal grains. We focus on the spatiotemporal dynamics and regulation of oligofructan biosynthesis and accumulation in developing barley grains (deduced from a combination of metabolite, transcript and proteome analyses). Finally, putative physiological functions of oligofructans in developing grains are discussed.
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Affiliation(s)
- Manuela Peukert
- Applied Biochemistry Group, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK-Gatersleben)Gatersleben, Germany
- University of CologneCologne, Germany
| | - Johannes Thiel
- Plant Architecture Group, IPK-GaterslebenGatersleben, Germany
| | - Hans-Peter Mock
- Applied Biochemistry Group, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK-Gatersleben)Gatersleben, Germany
| | - Doris Marko
- Department of Food Chemistry and Toxicology, University of ViennaVienna, Austria
| | | | - Andrea Matros
- Applied Biochemistry Group, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK-Gatersleben)Gatersleben, Germany
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Cruz-Bravo RK, Guevara-González RG, Ramos-Gómez M, Oomah BD, Wiersma P, Campos-Vega R, Loarca-Piña G. The fermented non-digestible fraction of common bean (Phaseolus vulgaris L.) triggers cell cycle arrest and apoptosis in human colon adenocarcinoma cells. GENES AND NUTRITION 2013; 9:359. [PMID: 24293398 DOI: 10.1007/s12263-013-0359-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 11/07/2013] [Indexed: 01/10/2023]
Abstract
Cancer is a leading cause of death worldwide with colorectal cancer (CRC) ranking as the third contributing to overall cancer mortality. Non-digestible compounds such as dietary fiber have been inversely associated with CRC in epidemiological in vivo and in vitro studies. In order to investigate the effect of fermentation products from a whole non-digestible fraction of common bean versus the short-chain fatty acid (SCFAs) on colon cancer cells, we evaluated the human gut microbiota fermented non-digestible fraction (hgm-FNDF) of cooked common bean (Phaseolus vulgaris L.) cultivar Negro 8025 and a synthetic mixture SCFAs, mimicking their concentration in the lethal concentration 50 (SCFA-LC50) of FNDF (hgm-FNDF-LC50), on the molecular changes in human colon adenocarcinoma cells (HT-29). Total mRNA from hgm-FNDF-LC50 and SCFA-LC50 treated HT-29 cells were used to perform qPCR arrays to determine the effect of the treatments on the transcriptional expression of 84 genes related to the p53-pathway. This study showed that both treatments inhibited cell proliferation in accordance with modulating RB1, CDC2, CDC25A, NFKB and E2F genes. Furthermore, we found an association between the induction of apoptosis and the modulation of APAF1, BID, CASP9, FASLG, TNFR10B and BCL2A genes. The results suggest a mechanism of action by which the fermentation of non-digestible compounds of common bean exert a beneficial effect better than the SCFA mixture by modulating the expression of antiproliferative and pro-apoptotic genes in HT-29 cells to a greater extent, supporting previous results on cell behavior, probably due to the participation of other compounds, such as phenolic fatty acids derivatives and biopetides.
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Affiliation(s)
- R K Cruz-Bravo
- Programa de Posgrado en Alimentos del Centro de la República (PROPAC), Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, 76010, Querétaro, QRO, Mexico
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Enhanced cellular uptake and in vitro antitumor activity of short-chain fatty acid acylated daunorubicin-GnRH-III bioconjugates. Eur J Med Chem 2012; 56:155-65. [PMID: 22967796 DOI: 10.1016/j.ejmech.2012.08.014] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Revised: 07/13/2012] [Accepted: 08/08/2012] [Indexed: 11/23/2022]
Abstract
Here we report on the synthesis and biochemical characterization (enzymatic stability, cellular uptake, in vitro antitumor activity, membrane interaction and GnRH-receptor binding affinity) of novel short-chain fatty acid (SCFA) acylated daunorubicin-GnRH-III bioconjugates, which may serve as drug delivery systems for targeted cancer chemotherapy. Ser in position 4 of GnRH-III was replaced by Lys, followed by the acylation of its ε-amino group with various fatty acids. SCFAs are potentially chemoprotective agents by suppressing the growth of cancer cells and therefore may enhance the antitumor activity of the bioconjugates. We found that all synthesized bioconjugates had high cytostatic effect in vitro, were stable in cell culture medium for 6 h and degraded in the presence of rat liver lysosomal homogenate leading to the formation of an oxime bond-linked daunorubicin-Lys as the smallest active metabolite. In the presence of α-chymotrypsin, all compounds were digested, the degradation rate strongly depending on the type of fatty acid. The bioconjugate containing Lys(nBu) in position 4 was taken up most efficiently by the cancer cells and exerted higher in vitro cytostatic effect than the previously developed GnRH-III((4)Lys(Ac), (8)Lys(Dau = Aoa)) or the parent GnRH-III(Dau = Aoa) bioconjugate. Our results could be explained by the increased binding affinity of the newly developed compound containing Lys(nBu) to the GnRH receptors.
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Abstract
It is proven that nuts contain essential macro- and micronutrients, e.g. fatty acids, vitamins and dietary fibre (DF). Fermentation of DF by the gut microflora results in the formation of SCFA which are recognised for their chemopreventive potential, especially by influencing cell growth. However, little is known about cellular response to complex fermentation samples of nuts. Therefore, we prepared and analysed (pH, SCFA, bile acids, tocopherol, antioxidant capacity) fermentation supernatant (fs) fractions of nuts (almonds, macadamias, hazelnuts, pistachios, walnuts) after in vitro fermentation and determined their effects on growth of HT29 cells as well as their genotoxic/anti-genotoxic potential. The fermented nut samples contained 2- to 3-fold higher amounts of SCFA than the faeces control, but considerable reduced levels of bile acids. While most of the investigated native nuts comprised relatively high amounts of tocopherol (α-tocopherol in almonds and hazelnuts and γ- and δ-tocopherol in pistachios and walnuts), rather low concentrations were found in the fs. All nut extracts and nut fs showed a strong antioxidant potential. Furthermore, all fs, except the fs pistachio, reduced growth of HT29 cells significantly. DNA damage induced by H₂O₂ was significantly reduced by the fs of walnuts after 15 min co-incubation of HT29 cells. In conclusion, this is the first study which presents the chemopreventive effects (reduction of tumour-promoting desoxycholic acid, rise in chemopreventive SCFA, protection against oxidative stress) of different nuts after in vitro digestion and fermentation, and shows the potential importance of nuts in the prevention of colon cancer.
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Kilner J, Waby JS, Chowdry J, Khan AQ, Noirel J, Wright PC, Corfe BM, Evans CA. A proteomic analysis of differential cellular responses to the short-chain fatty acids butyrate, valerate and propionate in colon epithelial cancer cells. MOLECULAR BIOSYSTEMS 2011; 8:1146-56. [PMID: 22075547 DOI: 10.1039/c1mb05219e] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The short chain fatty acids (SCFAs) are inhibitors of histone deacetylases (HDACi); they are produced naturally in the colon by fermentation. They affect cellular processes at a molecular and transcriptional level, the mechanisms of which may involve large numbers of proteins and integrated pathways. Butyrate is the most biologically potent of the SCFAs in colon epithelial cells, inhibiting human colon carcinoma cell proliferation and inducing apoptosis in vitro. In order to investigate the hypothesis that propionate and valerate possess unique and independent actions from butyrate, we combined proteomic and cellomic approaches for large-scale comparative analysis. Proteomic evaluation was undertaken using an iTRAQ tandem mass-spectrometry workflow and high-throughput High-content Analysis microscopy (HCA) was applied to generate cellomic information on the cell cycle and the cytoskeletal structure. Our results show that these SCFAs possess specific effects. Butyrate was shown to have more pronounced effects on the keratins and intermediate filaments (IFs); while valerate altered the β-tubulin isotypes' expression and the microtubules (MTs); propionate was involved in both mechanisms, displaying intermediate effects. These data suggest distinct physiological roles for SCFAs in colon epithelial function, offering new possibilities for cancer therapeutics.
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Affiliation(s)
- Josephine Kilner
- ChELSI Institute, Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, United Kingdom
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35
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Schlörmann W, Hiller B, Jahns F, Zöger R, Hennemeier I, Wilhelm A, Lindhauer MG, Glei M. Chemopreventive effects of in vitro digested and fermented bread in human colon cells. Eur J Nutr 2011; 51:827-39. [PMID: 22033853 DOI: 10.1007/s00394-011-0262-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2011] [Accepted: 10/07/2011] [Indexed: 12/19/2022]
Abstract
PURPOSE Bread as a staple food product represents an important source for dietary fibre consumption. Effects of wheat bread, wholemeal wheat bread and wholemeal rye bread on mechanisms which could have impact on chemoprevention were analysed in colon cells after in vitro fermentation. METHODS Effects of fermented bread samples on gene expression, glutathione S-transferase activity and glutathione content, differentiation, growth and apoptosis were investigated using the human colon adenoma cell line LT97. Additionally, apoptosis was studied in normal and tumour colon tissue by determination of caspase activities. RESULTS The expression of 76 genes (biotransformation, differentiation, apoptosis) was significantly upregulated (1.5-fold) in LT97 cells. The fermented bread samples were able to significantly increase glutathione S-transferase activity (1.8-fold) and glutathione content (1.4-fold) of the cells. Alkaline phosphatase activity as a marker of differentiation was also significantly enhanced (1.7-fold). The fermented bread samples significantly inhibited LT97 cell growth and increased the level of apoptotic cells (1.8-fold). Only marginal effects on apoptosis in tumour compared to normal tissue were observed. CONCLUSIONS This is the first study which presents chemopreventive effects of different breads after in vitro fermentation. In spite of differences in composition, the results were comparable between the bread types. Nevertheless, they indicate a potential involvement of this staple food product regarding the prevention of colon cancer.
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Affiliation(s)
- Wiebke Schlörmann
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, Dornburger Strasse 24, 07743, Jena, Germany.
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Putaala H, Mäkivuokko H, Tiihonen K, Rautonen N. Simulated colon fiber metabolome regulates genes involved in cell cycle, apoptosis, and energy metabolism in human colon cancer cells. Mol Cell Biochem 2011; 357:235-45. [DOI: 10.1007/s11010-011-0894-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2011] [Accepted: 05/17/2011] [Indexed: 12/12/2022]
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37
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Jahns F, Wilhelm A, Jablonowski N, Mothes H, Radeva M, Wölfert A, Greulich KO, Glei M. Butyrate suppresses mRNA increase of osteopontin and cyclooxygenase-2 in human colon tumor tissue. Carcinogenesis 2011; 32:913-20. [PMID: 21459756 DOI: 10.1093/carcin/bgr061] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The short chain fatty acid (SCFA) butyrate, a product of fermentation of dietary fiber in the human colon, is found to exert multiple regulatory processes in colon carcinogenesis. The aim of this study was to find out whether butyrate affects the tumor-promoting genes osteopontin (OPN) and cyclooxygenase (COX)-2, their respective proteins and/or their functional activity in matched normal, adenoma and tumor colon tissues obtained from 20 individuals at colon cancer surgery. Quantitative real-time polymerase chain reaction experiments showed increased levels of OPN and COX-2 messenger RNA in tumor tissues when compared with the adjacent normal samples (P < 0.001). The addition of butyrate reduced OPN and COX-2 mRNA expression in all tissue types compared with the related medium controls (tumor: P < 0.05). In tumor samples, a downregulation of up to median 35% (COX-2) and 50% (OPN) was observed, respectively. Thereby, tumors with lower levels of OPN basal expression were more sensitive to inhibition and vice versa for COX-2 in normal tissue. At the protein and enzyme level, which were determined by using western blot and enzyme immunometric assays, the impact of the SCFA was not clearly visible anymore. The active proteins of OPN and COX-2 (determined by prostaglandin E(2)) were found to correlate with their respective mRNA expression only in 50-63% of analyzed donors. For the first time, our data reveal new insights into the chemoprotective potential of butyrate by showing the suppression of OPN and COX-2 mRNA in primary human colon tissue with the strongest effects observed in tumors.
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Affiliation(s)
- F Jahns
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, Dornburger Straße 24, 07743 Jena, Germany.
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38
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Cruz-Bravo R, Guevara-Gonzalez R, Ramos-Gomez M, Garcia-Gasca T, Campos-Vega R, Oomah B, Loarca-Piña G. Fermented Nondigestible Fraction from Common Bean (Phaseolus vulgaris L.) Cultivar Negro 8025 Modulates HT-29 Cell Behavior. J Food Sci 2011; 76:T41-7. [DOI: 10.1111/j.1750-3841.2010.02025.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Raninen K, Lappi J, Mykkänen H, Poutanen K. Dietary fiber type reflects physiological functionality: comparison of grain fiber, inulin, and polydextrose. Nutr Rev 2011; 69:9-21. [PMID: 21198631 DOI: 10.1111/j.1753-4887.2010.00358.x] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Dietary fiber is a nutritional concept based not on physiological functions but on defined chemical and physical properties. Recent definitions of dietary fiber differentiate inherent plant cell wall-associated fiber from isolated or synthetic fiber. For the latter to be defined as fiber, beneficial physiological effects should be demonstrated, such as laxative effects, fermentability, attenuation of blood cholesterol levels, or postprandial glucose response. Grain fibers are a major natural source of dietary fiber worldwide, while inulin, a soluble indigestible fructose polymer isolated from chicory, and polydextrose, a synthetic indigestible glucose polymer, have more simple structures. Inulin and polydextrose show many of the same functionalities of grain fiber in the large intestine, in that they are fermentable, bifidogenic, and laxative. The reported effects on postprandial blood glucose and fasting cholesterol levels have been modest, but grain fibers also show variable effects. New biomarkers are needed to link the physiological functions of specific fibers with long-term health benefits.
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Affiliation(s)
- Kaisa Raninen
- Food and Health Research Centre, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
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Modification of anin vitromodel simulating the whole digestive process to investigate cellular endpoints of chemoprevention. Br J Nutr 2011; 105:678-87. [DOI: 10.1017/s0007114510004320] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In vitrogut fermentation systems are relevant tools to study health benefits of foodstuffs. Most of them are commonly used to investigate the degradation of nutrients or the development of gut flora. Using these models, strong cytotoxic effects of the resulting samples on cultured cells were observed. Hence, the aim of the present study was to develop a modifiedin vitrofermentation model that simulates the whole digestive tract and generates fermented samples that are suitable for testing in cell culture experiments. Wholemeal wheat flour (wwf) was digested and fermentedin vitrowith a fermentation model using different ox gall concentrations (41·6 and 0·6 g/l). The resulting fermentation supernatants (fs) were characterised for metabolites and biological effects in HT29 cells. The fermentation of wwf increased chemopreventive SCFA and decreased carcinogenic deoxycholic acid (DCA). The strong cytotoxic effects of the fs, which were partly due to cholic acid and DCA, were diminished by lowering the ox gall concentration, allowing the use of the samples in cell culture experiments. In conclusion, anin vitrodigestion model, which can be used to study the effects of foodstuffs on chemoprevention and gut health in colon cells, is introduced and its physiological relevance is demonstrated.
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41
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Oral Administration of Clostridium butyricum for Modulating Gastrointestinal Microflora in Mice. Curr Microbiol 2010; 62:512-7. [DOI: 10.1007/s00284-010-9737-8] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2010] [Accepted: 08/03/2010] [Indexed: 01/30/2023]
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42
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Fermented wheat aleurone induces enzymes involved in detoxification of carcinogens and in antioxidative defence in human colon cells. Br J Nutr 2010; 104:1101-11. [DOI: 10.1017/s0007114510001881] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Dietary fibre is fermented by the human gut flora resulting mainly in the formation of SCFA, for example, acetate, propionate and butyrate. SCFA, in particular butyrate, may be important for secondary cancer prevention by inducing apoptosis and inhibiting cell growth of cancer cells, thereby inhibiting the promotion and/or progression of cancer. Furthermore, SCFA could also act on primary cancer prevention by activation of detoxifying and antioxidative enzymes. We investigated the effects of fermented wheat aleurone on the expression of genes involved in stress response and toxicity, activity of drug-metabolising enzymes and anti-genotoxic potential. Aleurone was digested and fermented in vitro to obtain samples that reflect the content of the colon. HT29 cells and colon epithelial stripes were incubated with the resulting fermentation supernatant fractions (fs) and effects on mRNA expression of CAT, GSTP1 and SULT2B1 and enzyme activity of glutathione S-transferase (GST) and catalase (CAT) were measured. Fermented aleurone was also used to study the protection against H2O2-induced DNA damage in HT29 cells. The fs of aleurone significantly induced the mRNA expression of CAT, GSTP1 and SULT2B1 (HT29) and GSTP1 (epithelial stripes), respectively. The enzyme activities of GST (HT29) and CAT (HT29, epithelial stripes) were also unambiguously increased (1·4- to 3·7-fold) by the fs of aleurone. DNA damage induced by H2O2 was significantly reduced by the fs of aleurone after 48 h, whereupon no difference was observed compared with the faeces control. In conclusion, fermented aleurone is able to act on primary prevention by inducing mRNA expression and the activity of enzymes involved in detoxification of carcinogens and antioxidative defence.
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Borowicki A, Stein K, Scharlau D, Glei M. Fermentation supernatants of wheat ( Triticum aestivum L.) aleurone beneficially modulate cancer progression in human colon cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2010; 58:2001-2007. [PMID: 19954215 DOI: 10.1021/jf9032848] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Wheat aleurone contains high amounts of dietary fibers that are fermented by the microflora, resulting in the formation of short-chain fatty acids (SCFA), which are recognized for their chemopreventive potential. This study investigated the effects of fermented aleurone on growth, apoptosis, differentiation, and expression of several genes using two different human colon cell lines (LT97 and HT29). In LT97 cells, the fermentation supernatant (fs) aleurone reduced significantly the cell growth (EC(50) after 48 h = 7.6-8.3%), whereas the level of apoptotic cells was significantly increased (2.1-2.3-fold). Differentiation was enhanced in HT29 cells (1.8-fold) more than in LT97 cells (1.6-fold). Cell growth and apoptosis-related genes, namely WNT2B and p21, were induced by the fs (LT97, 1.7-3.3-fold; HT29, 7.9-22.2-fold). In conclusion, fermented wheat aleurone is able to act as a secondary chemopreventive agent by modulating parameters of cell growth and survival, whereas cells of an early transformation stage are more sensitive.
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Affiliation(s)
- Anke Borowicki
- Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University Jena, Dornburger Strasse 24, 07743 Jena, Germany.
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Abstract
Colorectal cancer is one of the leading causes of morbidity and mortality worldwide. An early detection of colorectal cancer determines therapeutic outcomes, while primary prevention remains a challenge. Our aim was to review the dietary, geographical and genetic factors in the causation and their possible role in the primary prevention of colorectal cancer. Data from experimental and clinical studies and population screening programmes were analysed to determine the factors responsible for causation of colorectal cancer. The role of dietary constituents, including the consumption of fat, red meat, fibre content, alcohol consumption, and other lifestyle issues, including obesity, lack of exercise and geographical variations in cancer prevalence were reviewed. The role of genetic and lifestyle factors in causation of colorectal cancer is evident from the experimental, clinical and population-based studies. Dietary factors, including the consumption of fat, fibre, red meat and alcohol, seem to have a significant influence in this regard. The role of micronutrients, vitamins, calcium may be relevant but remain largely unclear. In conclusion, there is ample evidence favouring the role of various dietary and lifestyle factors in the aetiology of colorectal cancer. Modification of these factors is an attractive option, which is likely to help in the primary prevention and reduced disease burden.
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Affiliation(s)
- Asghar Qasim
- Adelaide and Meath Hospital, Tallaght, Trinity College Dublin, AMNCH-Tallaght, Dublin 24, Ireland.
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Jiang L, Wang J, Liang S, Wang X, Cen P, Xu Z. Production of butyric acid from glucose and xylose with immobilized cells of Clostridium tyrobutyricum in a fibrous-bed bioreactor. Appl Biochem Biotechnol 2010; 160:350-359. [PMID: 18651247 DOI: 10.1007/s12010-008-8305-1] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2008] [Accepted: 06/24/2008] [Indexed: 11/28/2022]
Abstract
Butyric acid has many applications in chemical, food, and pharmaceutical industries. In the present study, Clostridium tyrobutyricum ATCC 25755 was immobilized in a fibrous-bed bioreactor to evaluate the performance of butyrate production from glucose and xylose. The results showed that the final concentration and yield of butyric acid were 13.70 and 0.46 g g(-1), respectively, in batch fermentation when 30 g L(-1) glucose was introduced into the bioreactor. Furthermore, high concentration 10.10 g L(-1) and yield 0.40 g g(-1) of butyric acid were obtained with 25 g L(-1) xylose as the carbon source. The immobilized cells of C. tyrobutyricum ensured similar productivity and yield from repeated batch fermentation. In the fed-batch fermentation, the final concentration of butyric acid was further improved to 24.88 g L(-1) with one suitable glucose feeding in the fibrous-bed bioreactor. C. tyrobutyricum immobilized in the fibrous-bed bioreactor would provide an economically viable fermentation process to convert the reducing sugars derived from plant biomass into the final bulk chemical (butyric acid).
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Affiliation(s)
- Ling Jiang
- South China University of Technology, Guangzhou, China
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46
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Boateng J, Verghese M, Panala V, Walker L, Shackelfor L. Protective Effects of Rice Bran on Chemically Induced Colon Tumorigenesis may be Due to Synergistic/Additive Properties of Bioactive Components. ACTA ACUST UNITED AC 2009. [DOI: 10.3923/ijcr.2009.153.166] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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47
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Fermented wheat aleurone inhibits growth and induces apoptosis in human HT29 colon adenocarcinoma cells. Br J Nutr 2009; 103:360-9. [DOI: 10.1017/s0007114509991899] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Fermentation of dietary fibre by the gut microflora may enhance levels of SCFA, which are potentially chemoprotective against colon cancer. Functional food containing wheat aleurone may prevent cancer by influencing cell cycle and cell death. We investigated effects of fermented wheat aleurone on growth and apoptosis of HT29 cells. Wheat aleurone, flour and bran were digested and fermentedin vitro. The resulting fermentation supernatants (fs) were analysed for their major metabolites (SCFA, bile acids and ammonia). HT29 cells were treated for 24–72 h with the fs or synthetic mixtures mimicking the fs in SCFA, butyrate or deoxycholic acid (DCA) contents, and the influence on cell growth was determined. Fs aleurone was used to investigate the modulation of apoptosis and cell cycle. The fermented wheat samples contained two- to threefold higher amounts of SCFA than the faeces control (blank), but reduced levels of bile acids and increased concentrations of ammonia. Fs aleurone and flour equally reduced cell growth of HT29 more effectively than the corresponding blank and the SCFA mixtures. The EC50(48 h) ranged from 10 % (flour) to 19 % (blank). Markedly after 48 h, fs aleurone (10 %) significantly induced apoptosis and inhibited cell proliferation by arresting the cell cycle in the G0/G1 phase. In conclusion, fermentation of wheat aleurone results in a reduced level of tumour-promoting DCA, but higher levels of potentially chemopreventive SCFA. Fermented wheat aleurone is able to induce apoptosis and to block cell cycle – two essential markers of secondary chemoprevention.
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Li F, Hullar MAJ, Schwarz Y, Lampe JW. Human gut bacterial communities are altered by addition of cruciferous vegetables to a controlled fruit- and vegetable-free diet. J Nutr 2009; 139:1685-91. [PMID: 19640972 PMCID: PMC2728691 DOI: 10.3945/jn.109.108191] [Citation(s) in RCA: 132] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
In the human gut, commensal bacteria metabolize food components that typically serve as energy sources. These components have the potential to influence gut bacterial community composition. Cruciferous vegetables, such as broccoli and cabbage, contain distinctive compounds that can be utilized by gut bacteria. For example, glucosinolates can be hydrolyzed by certain bacteria, and dietary fibers can be fermented by a range of species. We hypothesized that cruciferous vegetable consumption would alter growth of certain bacteria, thereby altering bacterial community composition. We tested this hypothesis in a randomized, crossover, controlled feeding study. Fecal samples were collected from 17 participants at the end of 2 14-d intake periods: a low-phytochemical, low-fiber basal diet (i.e. refined grains without fruits or vegetables) and a high ("double") cruciferous vegetable diet [basal diet + 14 g cruciferous vegetables/(kg body weightd)]. Fecal bacterial composition was analyzed by the terminal restriction fragment length polymorphism (tRFLP) method using the bacterial 16S ribosomal RNA gene and nucleotide sequencing. Using blocked multi-response permutation procedures analysis, we found that overall bacterial community composition differed between the 2 consumption periods (delta = 0.603; P = 0.011). The bacterial community response to cruciferous vegetables was individual-specific, as revealed by nonmetric multidimensional scaling ordination analysis. Specific tRFLP fragments that characterized each of the diets were identified using indicator species analysis. Putative species corresponding to these fragments were identified through gene sequencing as Eubacterium hallii, Phascolarctobacterium faecium, Burkholderiales spp., Alistipes putredinis, and Eggerthella spp. In conclusion, human gut bacterial community composition was altered by cruciferous vegetable consumption, which could ultimately influence gut metabolism of bioactive food components and host exposure to these compounds.
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Affiliation(s)
- Fei Li
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109 and Interdisplinary Graduate Program in Nutritional Sciences, University of Washington, Seattle, WA 98195
| | - Meredith A. J. Hullar
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109 and Interdisplinary Graduate Program in Nutritional Sciences, University of Washington, Seattle, WA 98195
| | - Yvonne Schwarz
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109 and Interdisplinary Graduate Program in Nutritional Sciences, University of Washington, Seattle, WA 98195
| | - Johanna W. Lampe
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109 and Interdisplinary Graduate Program in Nutritional Sciences, University of Washington, Seattle, WA 98195
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Campos-Vega R, Reynoso-Camacho R, Pedraza-Aboytes G, Acosta-Gallegos J, Guzman-Maldonado S, Paredes-Lopez O, Oomah B, Loarca-Piña G. Chemical Composition and In Vitro Polysaccharide Fermentation of Different Beans (Phaseolus vulgaris L.). J Food Sci 2009; 74:T59-65. [DOI: 10.1111/j.1750-3841.2009.01292.x] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Scharlau D, Borowicki A, Habermann N, Hofmann T, Klenow S, Miene C, Munjal U, Stein K, Glei M. Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res 2009; 682:39-53. [PMID: 19383551 DOI: 10.1016/j.mrrev.2009.04.001] [Citation(s) in RCA: 236] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2008] [Revised: 04/08/2009] [Accepted: 04/14/2009] [Indexed: 05/27/2023]
Abstract
Dietary fibres are indigestible food ingredients that reach the colon and are then fermented by colonic bacteria, resulting mainly in the formation of short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate. Those SCFA, especially butyrate, are recognised for their potential to act on secondary chemoprevention by slowing growth and activating apoptosis in colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different drug metabolising enzymes. This can reduce the burden of carcinogens and, therefore, decrease the number of mutations, reducing cancer risk. Activation of GSTs by butyrate has been studied on mRNA, protein, and enzyme activity level by real-time RT-PCR, cDNA microarrays, Western blotting, or photometrical approaches, respectively. Butyrate had differential effects in colon cells of different stages of cancer development. In HT29 tumour cells, e.g., mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced. In LT97 adenoma cells, GSTM3, GSTT2, and MGST3 were induced, whereas GSTA2, GSTT2, and catalase (CAT) were elevated in primary colon cells. Colon cells of different stages of carcinogenesis differed in post-transcriptional regulatory mechanisms because butyrate increased protein levels of different GST isoforms and total GST enzyme activity in HT29 cells, whereas in LT97 cells, GST protein levels and activity were slightly reduced. Because butyrate increased histone acetylation and phosphorylation of ERK in HT29 cells, inhibition of histone deacetylases and the influence on MAPK signalling are possible mechanisms of GST activation by butyrate. Functional consequences of this activation include a reduction of DNA damage caused by carcinogens like hydrogen peroxide or 4-hydroxynonenal (HNE) in butyrate-treated colon cells. Treatment of colon cells with the supernatant from an in vitro fermentation of inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells. Additional animal and human studies are needed to define the exact role of dietary fibre and butyrate in inducing GST activity and reducing the risk of colon cancer.
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Affiliation(s)
- Daniel Scharlau
- Institute for Nutrition, Friedrich Schiller University Jena, Dornburger Strasse 24, 07743 Jena, Germany.
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