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1
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Hussein MA, Al-zaban MI, Mahmoud YA, Al-Doaiss AA, Bahshwan SM, El-Dougdoug KA, EL-Shanshory MR. How does a Saccharomyces cerevisiae extract influence the components of isolated rotavirus particles from stool samples collected in a clinical setting from children? Saudi J Biol Sci 2024; 31:104031. [PMID: 38946847 PMCID: PMC11214517 DOI: 10.1016/j.sjbs.2024.104031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 05/21/2024] [Accepted: 05/25/2024] [Indexed: 07/02/2024] Open
Abstract
Human Rotavirus (HRV) is the causative pathogen of severe acute enteric infections that cause mortality among children worldwide. This study focuses on developing a new and effective treatment for rotavirus infection using an extract from Saccharomyces cerevisiae, aiming to make this treatment easily accessible to everyone. 15 antigens and 26 antibodies were detected in serum and stool using ELISA. The titers of HRVq1, HRVq2, HRVC1, and HRVC2 on Vero cells were determined to be 1.2x106, 3.0x106, 4.2x106, and 7.5x105 (Plaque forming unit, PFU/ml) four days after infection, respectively. The HRVq1 isolate induced cytopathic effects, i.e., forming multinucleated, rounded, enlarged, and expanding gigantic cells. RT-PCR identified this isolate, and the accession number 2691714 was assigned to GeneBank. The molecular docking analysis revealed that nonstructural proteins (NSPs) NSP1, NSP2, NSP3, NSP4, NSP5, and NSP6 exhibited significant binding with RNA. NSP2 demonstrated the highest binding affinity and the lowest binding energy (-8.9 kcal/mol). This affinity was maintained via hydrophobic interactions and hydrogen bonds spanning in length from 1.12 Å to 3.11 Å. The ADMET and bioactivity predictions indicated that the yeast extract possessed ideal solubility, was nontoxic, and did not cause cancer. The inhibitory constant values predicted for the S. cerevisiae extract in the presence of HRV vital proteins varied from 5.32 to 7.45 mM, indicating its potential as a viable drug candidate. Saccharomyces cerevisiae extract could be utilized as a dietary supplement to combat HRV as an alternative dietary supplement.
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Affiliation(s)
- Mona A.M. Hussein
- Botany Department, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Mayasar I. Al-zaban
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Yahia A.G. Mahmoud
- Botany Department, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Amin A. Al-Doaiss
- Biology Department, College of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia
| | - Safia M.A. Bahshwan
- Biological Sciences Department, College of Science and Arts, King Abdulaziz University, Rabigh 21911, Saudi Arabia
| | - Khalid A. El-Dougdoug
- Microbiology Department, Faculty of Agriculture, Ain Shams University, PO Box 68, Hadayek Shobra 11241, Cairo, Egypt
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2
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Huang H, Wang Q, Yang Y, Zhong W, He F, Li J. The mycobiome as integral part of the gut microbiome: crucial role of symbiotic fungi in health and disease. Gut Microbes 2024; 16:2440111. [PMID: 39676474 PMCID: PMC11651280 DOI: 10.1080/19490976.2024.2440111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 11/27/2024] [Accepted: 12/04/2024] [Indexed: 12/17/2024] Open
Abstract
The gut mycobiome significantly affects host health and immunity. However, most studies have focused on symbiotic bacteria in the gut microbiome, whereas less attention has been given to symbiotic fungi. Although fungi constitute only 0.01%-0.1% of the gut microbiome, their larger size and unique immunoregulatory functions make them significant. Factors like diet, antimicrobials use, and age can disrupt the fungal community, leading to dysbiosis. Fungal-bacterial-host immune interactions are critical in maintaining gut homeostasis, with fungi playing a role in mediating immune responses such as Th17 cell activation. This review highlights methods for studying gut fungi, the composition and influencing factors of the gut mycobiome, and its potential in therapeutic interventions for intestinal and hepatic diseases. We aim to provide new insights into the underexplored role of gut fungi in human health.
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Affiliation(s)
- Hui Huang
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
- Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, P. R. China
| | - Qiurong Wang
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
- Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, P. R. China
| | - Ying Yang
- Department of Gastroenterology, Sichuan Fifth People’s Hospital, Chengdu, China
| | - Wei Zhong
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
| | - Feng He
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
- Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, P. R. China
| | - Jun Li
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
- Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, P. R. China
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Razali FN, Teoh WY, Ramli MZ, Loo CY, Gnanaraj C. Role of prebiotics, probiotics, and synbiotics in the management of colonic disorders. ADVANCED DRUG DELIVERY SYSTEMS FOR COLONIC DISORDERS 2024:243-270. [DOI: 10.1016/b978-0-443-14044-0.00002-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Elahi Z, Shariati A, Bostanghadiri N, Dadgar-Zankbar L, Razavi S, Norzaee S, Vazirbani Arasi S, Darban-Sarokhalil D. Association of Lactobacillus, Firmicutes, Bifidobacterium, Clostridium, and Enterococcus with colorectal cancer in Iranian patients. Heliyon 2023; 9:e22602. [PMID: 38089982 PMCID: PMC10711133 DOI: 10.1016/j.heliyon.2023.e22602] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 11/08/2023] [Accepted: 11/15/2023] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the primary causes of cancer-associated deaths worldwide, and growing evidence shows that alteration in the gut microbiota may be a contributing factor to the development and progression of the disease. This study investigates the correlation between CRC and specific intestinal microbiota abundance, including Firmicutes, Lactobacillus, Enterococcus, Clostridium, and Bifidobacterium. MATERIAL AND METHODS In this study, 100 CRC samples and adjacent normal tissues were obtained from Iranian patients. Afterward, we assessed the abundance of the mentioned bacteria in matched tumor and normal tissue samples from 100 CRC patients, by TaqMan quantitative real-time polymerase chain reaction (qPCR). RESULTS Most of the patients (55 %) had grade II cancer (moderately differentiated), followed by grade III (poorly Differentiated) in 19 %, and the distribution of the tumor location was 65 % in the colon and 35 % in the rectum. Our research showed a substantial difference in the relative abundance of specific bacteria in tumors and healthy tissues. To this end, four genera of bacteria, including Bifidobacterium, Lactobacillus, Clostridium, and Firmicutes, exhibited statistically significant reductions in tumor tissues compared to adjacent normal tissue (p < 0.05). Conversely, Enterococcus demonstrated a statistically significant increase in tumor tissue samples (p < 0.05). Noteworthy, statistical analysis revealed a significant relationship between Enterococcus and prior cancer (p < 0.05). CONCLUSIONS These findings provide significant insight into the complex association between the gut microbiota and CRC and may pave the way for future research on novel screening methods, preventive measures, and therapeutic strategies targeting the gut microbiota in CRC patients.
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Affiliation(s)
- Zahra Elahi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Aref Shariati
- Student Research Committee, Khomein University of Medical Sciences, Khomein, Iran
- Molecular and Medicine Research Centre, Khomein University of Medical Sciences, Khomein, Iran
| | - Narjess Bostanghadiri
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Leila Dadgar-Zankbar
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Samira Norzaee
- Research Center for Environmental Health Technology, Iran University of Medical Sciences, Tehran, Iran
- Department of Environmental Health Engineering, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Davood Darban-Sarokhalil
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Zeighamy Alamdary S, Halimi S, Rezaei A, Afifirad R. Association between Probiotics and Modulation of Gut Microbial Community Composition in Colorectal Cancer Animal Models: A Systematic Review (2010-2021). THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2023; 2023:3571184. [PMID: 37719797 PMCID: PMC10505085 DOI: 10.1155/2023/3571184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 07/09/2023] [Accepted: 07/21/2023] [Indexed: 09/19/2023]
Abstract
Background Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies and is considered the third major cause of mortality globally. Probiotics have been shown to protect against the CRC cascade in numerous studies. Aims The goal of this systematic review was to gather the preclinical studies that examined the impact of probiotics on the alteration of gut microbiota profiles (bacterial communities) and their link to colorectal carcinogenesis as well as the potential processes involved. Methods The search was performed using Scopus, Web of Science, and PubMed databases. Five parameters were used to develop search filters: "probiotics," "prebiotics," "synbiotics," "colorectal cancer," and "animal model." Results Of the 399 full texts that were screened, 33 original articles met the inclusion criteria. According to the current findings, probiotics/synbiotics could significantly attenuate aberrant crypt foci (ACF) formation, restore beneficial bacteria in the microbiota population, increase short-chain fatty acids (SCFAs), and change inflammatory marker expression. Conclusions The present systematic review results indicate that probiotics could modulate the gut microbial composition and immune regulation to combat/inhibit CRC in preclinical models. However, where the evidence is more limited, it is critical to transfer preclinical research into clinical data.
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Affiliation(s)
| | - Shahnaz Halimi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Rezaei
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Roghayeh Afifirad
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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6
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Masood M, Nasser MI. Gut microbial metabolites and colorectal cancer. MICROBIAL BIOMOLECULES 2023:353-373. [DOI: 10.1016/b978-0-323-99476-7.00011-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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7
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Yinhang W, Wei W, Jing Z, Qing Z, Yani Z, Yangyanqiu W, Shuwen H. Biological roles of toll-like receptors and gut microbiota in colorectal cancer. Future Microbiol 2022; 17:1071-1089. [PMID: 35916158 DOI: 10.2217/fmb-2021-0072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most considerably common malignancies of the alimentary system, with high mortality and incidence rates. The present study suggested that the occurrence of CRC is closely related to bacteria, as the large intestine is a gathering place for human micro-organisms. However, the nosogenesis of bacteria leading to tumorigenesis is still obscure. Recently, many studies have reported that toll-like receptors and their related molecular pathways are involved in the process of gut micro-organisms generating CRC. Gut micro-organisms can promote or inhibit the development of CRC via binding to special toll-like receptors. In this paper, the authors review the relationship among toll-like receptors, gut micro-organisms and CRC in order to provide a reference for future tumor immunotherapy and targeted therapy.
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Affiliation(s)
- Wu Yinhang
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,The Second School of Clinical Medicine, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang Province, 310053, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Wu Wei
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhuang Jing
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhou Qing
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhou Yani
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Graduate School of Medicine Faculty, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou, Zhejiang Province, 310058, China
| | - Wang Yangyanqiu
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Graduate School of Medicine Faculty, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou, Zhejiang Province, 310058, China
| | - Han Shuwen
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
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8
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Rana D, Salave S, Perla A, Nadkarni A, Kohle S, Jindal AB, Mandoli A, Dwivedi P, Benival D. Bugs as Drugs: Understanding the Linkage between Gut Microbiota and Cancer Treatment Microbiome in Cancer Therapy. Curr Drug Targets 2022; 23:869-888. [PMID: 35264088 DOI: 10.2174/1389450123666220309101345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/03/2022] [Accepted: 01/12/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND The commensal microbiota is known to regulate host physiology. Dysbiosis or compromised Resilience in the microbial ecology is related to the impending risk of cancer. A potential link between cancer and microbiota is indicated by a lot of evidence. OBJECTIVE The current review explores in detail the various links leading to and /or facilitating oncogenesis, providing sound reasoning or a basis for its utilization as potential therapeutic targets. The present review emphasizes the existing knowledge of the microbiome in cancer and further elaborates on the factors like genetic modifications, effects of dietary components, and environmental agents that are considered to assess the direct and indirect effect of microbes in the process of oncogenesis and on the host's health. Strategies modulating the microbiome and novel biotherapeutics are also discussed. Pharmacomicrobiomics is one such niche accounting for the interplay between the microbiome, xenobiotic, and host responses is also looked upon. METHODS The literature search strategy for this review was conducted by following the methodology of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The method includes the collection of data from different search engines like PubMed, ScienceDirect, SciFinder etc. to get coverage of relevant literature for accumulating appropriate information regarding microbiome, cancer, and their linkages. RESULTS These considerations are made to expand the existing literature on the role of gut microbiota on the host's health, the interaction between host and microbiota, and the reciprocal relationship between the microbiome and modified neoplastic cells. CONCLUSION Potential therapeutic implications of cancer microbiomes that are yet unexplored and have rich therapeutic dividends improving human health are discussed in detail in this review.
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Affiliation(s)
- Dhwani Rana
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Sagar Salave
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Akhil Perla
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Akanksha Nadkarni
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Shital Kohle
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Anil B Jindal
- Department of Pharmacy, Birla Institute of Technology and Science Pilani (BITS PILANI), Pilani Campus, Rajasthan, 333031, India
| | - Amit Mandoli
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Pradeep Dwivedi
- Department of Pharmacology, All India Institute of Medical Sciences- Jodhpur (AIIMS), 342005, India
| | - Derajram Benival
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
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Ojwach J, Adetunji AI, Mutanda T, Mukaratirwa S. Oligosaccharides production from coprophilous fungi: An emerging functional food with potential health-promoting properties. BIOTECHNOLOGY REPORTS (AMSTERDAM, NETHERLANDS) 2022; 33:e00702. [PMID: 35127459 PMCID: PMC8803601 DOI: 10.1016/j.btre.2022.e00702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 01/08/2022] [Accepted: 01/13/2022] [Indexed: 11/26/2022]
Abstract
Functional foods are essential food products that possess health-promoting properties for the treatment of infectious diseases. In addition, they provide energy and nutrients, which are required for growth and survival. They occur as prebiotics or dietary supplements, including oligosaccharides, processed foods, and herbal products. However, oligosaccharides are more efficiently recognized and utilized, as they play a fundamental role as functional ingredients with great potential to improve health in comparison to other dietary supplements. They are low molecular weight carbohydrates with a low degree of polymerization. They occur as fructooligosaccharide (FOS), inulooligosaccharadie (IOS), and xylooligosaccahride (XOS), depending on their monosaccharide units. Oligosaccharides are produced by acid or chemical hydrolysis. However, this technique is liable to several drawbacks, including inulin precipitation, high processing temperature, low yields, and high production costs. As a consequence, the application of microbial enzymes for oligosaccharide production is recognized as a promising strategy. Microbial enzymatic production of FOS and IOS occurs by submerged or solid-state fermentation in the presence of suitable substrates (sucrose, inulin) and catalyzed by fructosyltransferases and inulinases. Incorporation of FOS and IOS enriches the rheological and physiological characteristics of foods. They are used as low cariogenic sugar substitutes, suitable for diabetics, and as prebiotics, probiotics and nutraceutical compounds. In addition, these oligosaccharides are employed as anticancer, antioxidant agents and aid in mineral absorption, lipid metabolism, immune regulation etc. This review, therefore, focuses on the occurrence, physico-chemical characteristics, and microbial enzymatic synthesis of FOS and IOS from coprophilous fungi. In addition, the potential health benefits of these oligosaccharides were discussed in detail.
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Affiliation(s)
- Jeff Ojwach
- School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom
- Department of Biodiversity and Conservation Biology, Faculty of Natural Science, University of the Western Cape, Private Bag X17 Bellville 7530, South Africa
- School of Life Sciences, College of Agriculture Engineering and Science, University of KwaZulu-Natal (Westville Campus), Private Bag X54001, Durban 4000, South Africa
| | - Adegoke Isiaka Adetunji
- School of Life Sciences, College of Agriculture Engineering and Science, University of KwaZulu-Natal (Westville Campus), Private Bag X54001, Durban 4000, South Africa
| | - Taurai Mutanda
- Centre for Algal Biotechnology, Department of Nature Conservation, Faculty of Natural Sciences, Mangosuthu University of Technology, P.O. Box 12363, Jacobs 4026, Durban, South Africa
| | - Samson Mukaratirwa
- School of Life Sciences, College of Agriculture Engineering and Science, University of KwaZulu-Natal (Westville Campus), Private Bag X54001, Durban 4000, South Africa
- One Health Center for Zoonoses and Tropical Veterinary Medicine, Ross University, School of Veterinary Medicine, P.O. Box 334, Basseterre, St. Kitts, West Indies
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10
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D'Amico F, Barone M, Tavella T, Rampelli S, Brigidi P, Turroni S. Host microbiomes in tumor precision medicine: how far are we? Curr Med Chem 2022; 29:3202-3230. [PMID: 34986765 DOI: 10.2174/0929867329666220105121754] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/13/2021] [Accepted: 11/22/2021] [Indexed: 11/22/2022]
Abstract
The human gut microbiome has received a crescendo of attention in recent years, due to the countless influences on human pathophysiology, including cancer. Research on cancer and anticancer therapy is constantly looking for new hints to improve the response to therapy while reducing the risk of relapse. In this scenario, the gut microbiome and the plethora of microbial-derived metabolites are considered a new opening in the development of innovative anticancer treatments for a better prognosis. This narrative review summarizes the current knowledge on the role of the gut microbiome in the onset and progression of cancer, as well as in response to chemo-immunotherapy. Recent findings regarding the tumor microbiome and its implications for clinical practice are also commented on. Current microbiome-based intervention strategies (i.e., prebiotics, probiotics, live biotherapeutics and fecal microbiota transplantation) are then discussed, along with key shortcomings, including a lack of long-term safety information in patients who are already severely compromised by standard treatments. The implementation of bioinformatic tools applied to microbiomics and other omics data, such as machine learning, has an enormous potential to push research in the field, enabling the prediction of health risk and therapeutic outcomes, for a truly personalized precision medicine.
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Affiliation(s)
- Federica D'Amico
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Monica Barone
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Teresa Tavella
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Simone Rampelli
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Patrizia Brigidi
- Microbiome Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
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11
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Hua Y, Lou YX, Li C, Sun JY, Sun W, Kong XQ. Clinical outcomes of bariatric surgery - Updated evidence. Obes Res Clin Pract 2021; 16:1-9. [PMID: 34848153 DOI: 10.1016/j.orcp.2021.11.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/15/2021] [Accepted: 11/22/2021] [Indexed: 12/20/2022]
Abstract
Obesity has grown to become a major health problem over the past few decades. Obesity-related comorbidities, such as diabetes mellitus, hypertension, obstructive sleep apnea, and dyslipidemia, are inextricably linked with increased adverse clinical consequences and mortality. Compared with other strategies for obesity, bariatric surgery is efficient in weight loss and has been proved to exert positive effects on obesity-related risk factors. This broad improvement in risk factors has resulted in substantial remission or reductions of comorbidities and better performance on clinical outcomes, including cardiovascular diseases, cancer, and mortality. With the development of surgical procedures, the safety of bariatric surgery has been validated and the rate of peri-operative death is low all over the world. Nonetheless, surgeons ought to be careful about potential complications, such as nutrition deficiencies, psychological disorders, or new digestive tract tumors after surgery. For patients with obesity, bariatric surgery might be a precious and crucial tool to bring additional benefits including comorbidities protection and life span extension. All patients with obesity should be engaged in a union consultation group to select a suitable treatment.
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Affiliation(s)
- Yang Hua
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Yu-Xuan Lou
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Cong Li
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Jin-Yu Sun
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Wei Sun
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.
| | - Xiang-Qing Kong
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.
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12
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Moszak M, Szulińska M, Walczak-Gałęzewska M, Bogdański P. Nutritional Approach Targeting Gut Microbiota in NAFLD-To Date. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:1616. [PMID: 33567710 PMCID: PMC7916007 DOI: 10.3390/ijerph18041616] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/05/2021] [Accepted: 01/25/2021] [Indexed: 12/18/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a significant clinical and epidemiological problem that affects around 25% of the adult global population. A large body of clinical evidence highlights that NAFLD is associated with increased liver-related morbidity and mortality and an increased risk of cardiovascular disease, extrahepatic cancers, type 2 diabetes, and chronic kidney disease. Recently, a series of studies revealed the pivotal role of gut microbiota (GM) dysbiosis in NAFLD's pathogenesis. The GM plays an essential role in different metabolic pathways, including the fermentation of diet polysaccharides, energy harvest, choline regulation, and bile acid metabolism. One of the most critical factors in GM stabilization is the diet; therefore, nutritional therapyappearsto be a promising tool in NAFLD therapy. This paper aims to review the current knowledge regardingthe nutritional approach and its implications with GM and NAFLD treatment. We discuss the positive impact of probiotics, prebiotics, and symbiotics in a reverse dysbiosis state in NAFLD and show the potential beneficial effects of bioactive substances from the diet. The full description of the mechanism of action and comprehensive examination of the impact of nutritional interventions on GM modulation may, in the future, be a simple but essential tool supporting NAFLD therapy.
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Affiliation(s)
- Małgorzata Moszak
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| | - Monika Szulińska
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| | - Marta Walczak-Gałęzewska
- Department of Internal Medicine, Metabolic Disorders, and Hypertension, Poznań University of Medical Sciences, 61-701 Poznań, Poland;
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
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13
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Gut Microbiota and Colon Cancer: A Role for Bacterial Protein Toxins? Int J Mol Sci 2020; 21:ijms21176201. [PMID: 32867331 PMCID: PMC7504354 DOI: 10.3390/ijms21176201] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/25/2020] [Accepted: 08/26/2020] [Indexed: 02/06/2023] Open
Abstract
Accumulating evidence indicates that the human intestinal microbiota can contribute to the etiology of colorectal cancer. Triggering factors, including inflammation and bacterial infections, may favor the shift of the gut microbiota from a mutualistic to a pro-carcinogenic configuration. In this context, certain bacterial pathogens can exert a pro-tumoral activity by producing enzymatically-active protein toxins that either directly induce host cell DNA damage or interfere with essential host cell signaling pathways involved in cell proliferation, apoptosis, and inflammation. This review is focused on those toxins that, by mimicking carcinogens and cancer promoters, could represent a paradigm for bacterially induced carcinogenesis.
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14
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Liu CZ, Chen W, Wang MX, Wang Y, Chen LQ, Zhao F, Shi Y, Liu HJ, Dou XB, Liu C, Chen H. Dendrobium officinale Kimura et Migo and American ginseng mixture: A Chinese herbal formulation for gut microbiota modulation. Chin J Nat Med 2020; 18:446-459. [PMID: 32503736 DOI: 10.1016/s1875-5364(20)30052-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Indexed: 02/07/2023]
Abstract
Dendrobium officinale Kimura et Migo (D. officinale) is a famous traditional Chinese medicine (TCM). A mixture of D. officinale and American ginseng has been shown to enhance cell-mediated immunity, humoral immunity, and monocyte/macrophage functions in mice. Here, the effects of a D. officinale and American ginseng mixture on the structure of gut microbial community in dogs were examined using high-throughput 16S rRNA gene amplicon sequencing. The data revealed that while the mixture did not change the diversity of gut microbial community significantly, differences among individuals were significantly reduced. Furthermore, the mixture-responsive operational taxonomic units (OTUs) exhibited a phase-dependent expression pattern. Fifty-five OTUs were found to exhibit a mixture-induced expression pattern, among which one third were short-chain fatty acid (SCFA)-producing genera and the others were probiotic genera included Lactobacillus spp., Sutterella, Alistipes, Anaerovorax, Bilophila, Coprococcus, Gordonibacter, Oscillibacter, among others. By contrast, 36% of the OTUs exhibiting a mixture-repressed expression pattern were disease-associated microorganisms, and six genera, namely Actinomyces, Escherichia/Shigella, Fusobacterium, Slackia, Streptococcus and Solobacterium, were associated with cancer. In addition, five genera were closely associated with diabetes, namely Collinsella, Rothia, Howardella, Slackia and Intestinibacter. Our results indicate that this D. officinale and American ginseng mixture may be used as a prebiotic agent to enhance SCFA-producing genera and prevent gut dysbiosis.
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Affiliation(s)
- Cheng-Zhi Liu
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Wei Chen
- Hangzhou Huqing yu tang Traditional Chinese Medicine Mordernize Institute, Hangzhou 311100, China
| | - Mei-Xia Wang
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Ying Wang
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Li-Qing Chen
- Hangzhou Huqing yu tang Traditional Chinese Medicine Mordernize Institute, Hangzhou 311100, China
| | - Feng Zhao
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Ya Shi
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Hui-Jun Liu
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Xiao-Bing Dou
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Chao Liu
- Department of Orthopaedics, Sir Sun Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
| | - Huan Chen
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China.
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15
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Shen W, Sun J, Yao F, Lin K, Yuan Y, Chen Y, Han H, Li Z, Zou J, Jiao X. Microbiome in Intestinal Lavage Fluid May Be A Better Indicator in Evaluating The Risk of Developing Colorectal Cancer Compared with Fecal Samples. Transl Oncol 2020; 13:100772. [PMID: 32298987 PMCID: PMC7160452 DOI: 10.1016/j.tranon.2020.100772] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE Intestinal microbiota plays a vital role in the pathogenesis of colorectal cancer (CRC), which is crucial for assessing the risk and prognosis of CRC. Most studies regarding human gut microbiota mainly based on the feces, but the exact composition of microbiota vary significantly due to fecal composition is easily affected by many factors. We aim to evaluate whether intestinal lavage fluid (IVF) is a better substitution mirroring the gut microbiota. METHODS We performed 16S rRNA gene analysis on fecal and IVF samples from 30 CRC patients and 25 healthy individuals, comparison in luminal (feces) / mucosal (IVF) adherent bacterial community profiles were analyzed. RESULTS The difference between feces and IVF were observed, including the diversity and abundance of pathogenic bacteria (either in single strain or in co-occurrence pattern). IVF group shared 605 OTUs with the fecal group, but there was 94 OTUs only observed in fecal samples, while 247 OTUs were mainly existing in the IVF group. Among them, 27 vital bacterial species detected in IVF, while 10 critical species detected in fecal samples. The co-occurrence bacteria Fusobacteria Cluster and Proteobacteria Cluster 2 significantly increased in IVF than in control (P < .01), while Firmicutes Cluster 1, Firmicutes Cluster 2 and Proteobacteria Cluster 1 were markedly lower in IVF than in control (P < .001). In CRC feces, Fusobacteria Cluster was higher than in control (P < .05), but Firmicutes Cluster 1 was of substantially less abundance than in control (P < .001). Proteobacteria Cluster 2 was increased dramatically in IVF than in feces (P < .05), Firmicutes Cluster 1 were of substantially less abundance than in feces (P < .05). CONCLUSION Pathogenic microbiota is more abundant in IVF than in feces. Microbiota of IVF may closely be related to the mucosal-associated microbial communities, which benefit from elucidating the relationship of the intestinal microbiota and CRC carcinogenesis.
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Affiliation(s)
- Weitao Shen
- The second affiliated hospital of Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Jiayu Sun
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Fen Yao
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Kaihuang Lin
- The second affiliated hospital of Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Yumeng Yuan
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Yexi Chen
- The second affiliated hospital of Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Hui Han
- The second affiliated hospital of Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Zhiyang Li
- The second affiliated hospital of Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Juan Zou
- The second affiliated hospital of Shantou University Medical College, Shantou, Guangdong, China 515041.
| | - Xiaoyang Jiao
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China 515041.
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16
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Guarino MPL, Altomare A, Emerenziani S, Di Rosa C, Ribolsi M, Balestrieri P, Iovino P, Rocchi G, Cicala M. Mechanisms of Action of Prebiotics and Their Effects on Gastro-Intestinal Disorders in Adults. Nutrients 2020; 12:1037. [PMID: 32283802 PMCID: PMC7231265 DOI: 10.3390/nu12041037] [Citation(s) in RCA: 103] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 04/04/2020] [Accepted: 04/06/2020] [Indexed: 02/06/2023] Open
Abstract
In recent years, research has focused on the use of dietary fibers and prebiotics, since many of these polysaccharides can be metabolized by intestinal microbiota, leading to the production of short-chain fatty acids. The metabolites of prebiotic fermentation also show anti-inflammatory and immunomodulatory capabilities, suggesting an interesting role in the treatment of several pathological conditions. Galacto-oligosaccharide and short- and long-chain fructans (Fructo-oligosaccharides and inulin) are the most studied prebiotics, even if other dietary compounds seem to show the same features. There is an increasing interest in dietary strategies to modulate microbiota. The aim of this review is to explore the mechanisms of action of prebiotics and their effects on the principal gastro-intestinal disorders in adults, with a special focus on Galacto-oligosaccharides, Fructo-oligosaccharides, lactulose and new emerging substances which currently have evidence of prebiotics effects, such as xilooligosaccharides, soybean oligosaccharides, isomaltooligosaccharides, lactobionic acid, resistant starch and polyphenols.
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Affiliation(s)
- Michele Pier Luca Guarino
- Gastroenterology Unit, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy; (M.P.L.G.); (S.E.); (M.R.); (P.B.); (G.R.); (M.C.)
| | - Annamaria Altomare
- Gastroenterology Unit, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy; (M.P.L.G.); (S.E.); (M.R.); (P.B.); (G.R.); (M.C.)
| | - Sara Emerenziani
- Gastroenterology Unit, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
- (M.P.L.G.)
- (S.E.)
- (M.R.)
- (P.B.)
- (G.R.)
- (M.C.)
| | - Claudia Di Rosa
- Unit of Food Science and Human Nutrition, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy;
| | - Mentore Ribolsi
- Gastroenterology Unit, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy; (M.P.L.G.); (S.E.); (M.R.); (P.B.); (G.R.); (M.C.)
| | - Paola Balestrieri
- Gastroenterology Unit, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy; (M.P.L.G.); (S.E.); (M.R.); (P.B.); (G.R.); (M.C.)
| | - Paola Iovino
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, Università di Salerno, Via Allende, 84081 Salerno, Italy;
| | - Giulia Rocchi
- Gastroenterology Unit, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy; (M.P.L.G.); (S.E.); (M.R.); (P.B.); (G.R.); (M.C.)
| | - Michele Cicala
- Gastroenterology Unit, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy; (M.P.L.G.); (S.E.); (M.R.); (P.B.); (G.R.); (M.C.)
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17
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Qiu Q, Li Y, Fan Z, Yao F, Shen W, Sun J, Yuan Y, Chen J, Cai L, Xie Y, Liu K, Chen X, Jiao X. Gene Expression Analysis of Human Papillomavirus-Associated Colorectal Carcinoma. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5201587. [PMID: 32258125 PMCID: PMC7103040 DOI: 10.1155/2020/5201587] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 01/21/2020] [Accepted: 02/20/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE Human papillomavirus (HPV) antigens had been found in colorectal cancer (CRC) tissue, but little evidence demonstrates the association of HPV with oncogene mutations in CRC. We aim to elucidate the mutated genes that link HPV infection and CRC carcinogenesis. METHODS Cancerous and adjacent noncancerous tissues were obtained from CRC patients. HPV antigen was measured by using the immunohistochemical (IHC) technique. The differentially expressed genes (DEGs) in HPV-positive and HPV-negative tumor tissues were measured by using TaqMan Array Plates. The target genes were validated with the qPCR method. RESULTS 15 (31.9%) cases of CRC patients were observed to be HPV positive, in which HPV antigen was expressed in most tumor tissues rather than in adjacent noncancerous tissues. With TaqMan Array Plates analyses, we found that 39 differentially expressed genes (DEGs) were upregulated, while 17 DEGs were downregulated in HPV-positive CRC tissues compared with HPV-negative tissues. Four DEGs (MMP-7, MYC, WNT-5A, and AXIN2) were upregulated in tumor vs. normal tissues, or adenoma vs. normal tissue in TCGA, which was overlapped with our data. In the confirmation test, MMP-7, MYC, WNT-5A, and AXIN2 were upregulated in cancerous tissue compared with adjacent noncancerous tissue. MYC, WNT-5A, and AXIN2 were shown to be upregulated in HPV-positive CRC tissues when compared to HPV-negative tissues. CONCLUSION HPV-encoding genome may integrate into the tumor genomes that involved in multiple signaling pathways. Further genomic and proteomic investigation is necessary for obtaining a more comprehensive knowledge of signaling pathways associated with the CRC carcinogenesis.
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Affiliation(s)
- Qiancheng Qiu
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Yazhen Li
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China
- Jiangmen Central Hosptial (Affiliated Jiangmen Hospital of Sun Yat-Sen University), Guangdong 529000, China
| | - Zhiqiang Fan
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Fen Yao
- Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Wenjun Shen
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Jiayu Sun
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Yumeng Yuan
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Jinghong Chen
- Center for Disease Control and Prevention of Shantou, Guangdong 515041, China
| | - Leshan Cai
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Yanxuan Xie
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Kaixi Liu
- Shantou Central Hospital, Shantou, Guangdong 515041, China
| | - Xiang Chen
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Xiaoyang Jiao
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China
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18
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Castagneto-Gissey L, Casella-Mariolo J, Casella G, Mingrone G. Obesity Surgery and Cancer: What Are the Unanswered Questions? Front Endocrinol (Lausanne) 2020; 11:213. [PMID: 32351453 PMCID: PMC7174700 DOI: 10.3389/fendo.2020.00213] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 03/25/2020] [Indexed: 12/19/2022] Open
Abstract
Obesity has become a global epidemic with a soaring economic encumbrance due to its related morbidity and mortality. Amongst obesity-related conditions, cancer is indeed the most redoubtable. Bariatric surgery has been proven to be the most effective treatment for obesity and its associated metabolic and cardiovascular disorders. However, the understanding of whether and how bariatric surgery determines a reduction in cancer risk is limited. Obesity-related malignancies primarily include colorectal and hormone-sensitive (endometrium, breast, prostate) cancers. Additionally, esophago-gastric tumors are growing to be recognized as a new category mainly associated with post-bariatric surgery outcomes. In fact, certain types of surgical procedures have been described to induce the development and subsequent progression of pre-cancerous esophageal and gastric lesions. This emerging category is of great concern and further research is required to possibly prevent such risks. Published data has generated conflicting results. In fact, while overall cancer risk reduction was reported particularly in women, some authors showed no improvement or even increased cancer incidence. Although various studies have reported beneficial effects of surgery on risk of specific cancer development, fundamental insights into the pathogenesis of obesity-related cancer are indispensable to fully elucidate its mechanisms.
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Affiliation(s)
- Lidia Castagneto-Gissey
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
- *Correspondence: Lidia Castagneto-Gissey
| | | | - Giovanni Casella
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Geltrude Mingrone
- Division of Diabetes & Nutritional Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Division of Diabetes & Nutritional Sciences, Università Cattolica del Sacro Cuore Rome, Rome, Italy
- Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom
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19
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Fabbri A, Travaglione S, Rosadi F, Ballan G, Maroccia Z, Giambenedetti M, Guidotti M, Ødum N, Krejsgaard T, Fiorentini C. The Escherichia coli protein toxin cytotoxic necrotizing factor 1 induces epithelial mesenchymal transition. Cell Microbiol 2019; 22:e13138. [PMID: 31698538 DOI: 10.1111/cmi.13138] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 09/18/2019] [Accepted: 10/28/2019] [Indexed: 12/14/2022]
Abstract
Some toxigenic bacteria produce protein toxins with carcinogenic signatures, which either directly damage DNA or stimulate signalling pathways related to cancer. So far, however, only a few of them have been proved to favour the induction or progression of cancer. In this work, we report that the Rho-activating Escherichia coli protein toxin, cytotoxic necrotising factor 1 (CNF1), induces epithelial to mesenchymal transition (EMT) in intestinal epithelial cells. EMT is a crucial step in malignant tumour conversion and invasiveness. In the case of CNF1, it occurs by up-regulation of the transcription factors ZEB1 and Snail1, delocalisation of E-cadherin and β-catenin, activation of the serine/threonine kinase mTOR, accelerated wound healing, and invasion. However, our results highlight that nontransformed epithelial cells entail the presence of inflammatory factors, in addition to CNF1, to acquire a mesenchymal-like behaviour. All this suggests that the surrounding microenvironment, as well as the cell type, dramatically influences the CNF1 ability to promote carcinogenic traits.
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Affiliation(s)
- Alessia Fabbri
- Italian Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Sara Travaglione
- Italian Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Francesca Rosadi
- Italian Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Giulia Ballan
- Italian Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Zaira Maroccia
- Italian Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | | | - Marco Guidotti
- Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
| | - Niels Ødum
- LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Thorbjørn Krejsgaard
- LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Carla Fiorentini
- Italian Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.,Preclinical Research Section, Associazione Ricerca Terapie Oncologiche Integrate (ARTOI), Rome, Italy
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20
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Tarashi S, Siadat SD, Ahmadi Badi S, Zali M, Biassoni R, Ponzoni M, Moshiri A. Gut Bacteria and their Metabolites: Which One Is the Defendant for Colorectal Cancer? Microorganisms 2019; 7:E561. [PMID: 31766208 PMCID: PMC6920974 DOI: 10.3390/microorganisms7110561] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 08/22/2019] [Accepted: 09/04/2019] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC. However, several studies have already evaluated the different aspects of the association between microbiota and CRC. The current study aimed at reviewing and summarizing most of the studies on the modifications of gut bacteria detected in stool and tissue samples of CRC cases. In addition, the importance of metabolites derived from gut bacteria, their relationship with the microbiota, and epigenetic modifications have been evaluated.
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Affiliation(s)
- Samira Tarashi
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Sara Ahmadi Badi
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Mohammadreza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran;
| | - Roberto Biassoni
- Laboratory of Molecular Medicine, IRCCS Instituto Giannina Gaslini, 16147 Genova, Italy;
| | - Mirco Ponzoni
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
| | - Arfa Moshiri
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran;
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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21
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Liang D, Li M, Wei R, Wang J, Li Y, Jia W, Chen T. Strategy for Intercorrelation Identification between Metabolome and Microbiome. Anal Chem 2019; 91:14424-14432. [PMID: 31638380 DOI: 10.1021/acs.analchem.9b02948] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Accumulating evidence points to the strong and complicated associations between the metabolome and the microbiome, which play diverse roles in physiology and pathology. Various correlation analysis approaches were applied to identify microbe-metabolite associations. Given the strengths and weaknesses of the existing methods and considering the characteristics of different types of omics data, we designed a special strategy, called Generalized coRrelation analysis for Metabolome and Microbiome (GRaMM), for the intercorrelation discovery between the metabolome and microbiome. GRaMM can properly deal with two types of omics data, the effect of confounders, and both linear and nonlinear correlations by integrating several complementary methods such as the classical linear regression, the emerging maximum information coefficient (MIC), the metabolic confounding effect elimination (MCEE), and the centered log-ratio transformation (CLR). GRaMM contains four sequential computational steps: (1) metabolic and microbial data preprocessing, (2) linear/nonlinear type identification, (3) data correction and correlation detection, and (4) p value correction. The performances of GRaMM, including the accuracy, sensitivity, specificity, false positive rate, applicability, and effects of preprocessing and confounder adjustment steps, were evaluated and compared with three other methods in multiple simulated and real-world datasets. To our knowledge, GRaMM is the first strategy designed for the intercorrelation analysis between metabolites and microbes. The Matlab function and an R package were developed and are freely available for academic use (comply with GNU GPL.V3 license).
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Affiliation(s)
- Dandan Liang
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233 , China
| | - Mengci Li
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233 , China.,School of Biomedical Engineering and Med-X Research Institute , Shanghai Jiao Tong University , Shanghai 200030 , China
| | - Runmin Wei
- University of Hawaii Cancer Center , 701 Ilalo Street , Honolulu , Hawaii 96813 , United States
| | - Jingye Wang
- University of Hawaii Cancer Center , 701 Ilalo Street , Honolulu , Hawaii 96813 , United States
| | - Yitao Li
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233 , China.,Hong Kong Traditional Chinese Medicine Phenome Research Centre, School of Chinese Medicine , Hong Kong Baptist University , Kowloon Tong , Hong Kong 999077 , China
| | - Wei Jia
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233 , China.,University of Hawaii Cancer Center , 701 Ilalo Street , Honolulu , Hawaii 96813 , United States.,Hong Kong Traditional Chinese Medicine Phenome Research Centre, School of Chinese Medicine , Hong Kong Baptist University , Kowloon Tong , Hong Kong 999077 , China
| | - Tianlu Chen
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233 , China
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22
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Martin OCB, Bergonzini A, D'Amico F, Chen P, Shay JW, Dupuy J, Svensson M, Masucci MG, Frisan T. Infection with genotoxin-producing Salmonella enterica synergises with loss of the tumour suppressor APC in promoting genomic instability via the PI3K pathway in colonic epithelial cells. Cell Microbiol 2019; 21:e13099. [PMID: 31414579 PMCID: PMC6899655 DOI: 10.1111/cmi.13099] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 07/16/2019] [Accepted: 07/30/2019] [Indexed: 12/18/2022]
Abstract
Several commensal and pathogenic Gram‐negative bacteria produce DNA‐damaging toxins that are considered bona fide carcinogenic agents. The microbiota of colorectal cancer (CRC) patients is enriched in genotoxin‐producing bacteria, but their role in the pathogenesis of CRC is poorly understood. The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in the majority of sporadic CRCs. We investigated whether the loss of APC alters the response of colonic epithelial cells to infection by Salmonella enterica, the only genotoxin‐producing bacterium associated with cancer in humans. Using 2D and organotypic 3D cultures, we found that APC deficiency was associated with sustained activation of the DNA damage response, reduced capacity to repair different types of damage, including DNA breaks and oxidative damage, and failure to induce cell cycle arrest. The reduced DNA repair capacity and inability to activate adequate checkpoint responses was associated with increased genomic instability in APC‐deficient cells exposed to the genotoxic bacterium. Inhibition of the checkpoint response was dependent on activation of the phosphatidylinositol 3‐kinase pathway. These findings highlight the synergistic effect of the loss of APC and infection with genotoxin‐producing bacteria in promoting a microenvironment conducive to malignant transformation.
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Affiliation(s)
- Océane C B Martin
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
| | - Anna Bergonzini
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.,Department of Molecular Biology, Umeå University, Umeå, Sweden
| | - Federica D'Amico
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
| | - Puran Chen
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Jerry W Shay
- Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Jacques Dupuy
- INRA, ToxAlim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France
| | - Mattias Svensson
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Maria G Masucci
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
| | - Teresa Frisan
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.,Department of Molecular Biology, Umeå University, Umeå, Sweden
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23
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Saus E, Iraola-Guzmán S, Willis JR, Brunet-Vega A, Gabaldón T. Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential. Mol Aspects Med 2019; 69:93-106. [PMID: 31082399 PMCID: PMC6856719 DOI: 10.1016/j.mam.2019.05.001] [Citation(s) in RCA: 209] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 05/08/2019] [Indexed: 02/08/2023]
Abstract
The gastrointestinal tract harbors most of the microbiota associated with humans. In recent years, there has been a surge of interest in assessing the relationships between the gut microbiota and several gut alterations, including colorectal cancer. Changes in the gut microbiota in patients suffering colorectal cancer suggest a possible role of host-microbe interactions in the origin and development of this malignancy and, at the same time, open the door for novel ways of preventing, diagnosing, or treating this disease. In this review we survey current knowledge on the healthy microbiome of the gut and how it is altered in colorectal cancer and other related disease conditions. In describing past studies we will critically assess technical limitations of different approaches and point to existing challenges in microbiome research. We will have a special focus on host-microbiome interaction mechanisms that may be important to explain how dysbiosis can lead to chronic inflammation and drive processes that influence carcinogenesis and tumor progression in colon cancer. Finally, we will discuss the potential of recent developments of novel microbiota-based therapeutics and diagnostic tools for colorectal cancer.
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Affiliation(s)
- Ester Saus
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Susana Iraola-Guzmán
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Jesse R Willis
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Anna Brunet-Vega
- Oncology Service, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.
| | - Toni Gabaldón
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain; ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain.
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24
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Wang Z, Qi Q. Gut microbial metabolites associated with HIV infection. Future Virol 2019; 14:335-347. [PMID: 31263508 PMCID: PMC6595475 DOI: 10.2217/fvl-2019-0002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 04/25/2019] [Indexed: 02/06/2023]
Abstract
HIV infection has been associated with alterations in gut microbiota and related microbial metabolite production. However, the mechanisms of how these functional microbial metabolites may affect HIV immunopathogenesis and comorbidities, such as cardiovascular disease and other metabolic diseases, remain largely unknown. Here we review the current understanding of gut microbiota and related metabolites in the context of HIV infection. We focus on several bacteria-produced metabolites, including tryptophan catabolites, short-chain fatty acids and trimethylamine-N-oxide (TMAO), and discuss their implications in HIV infection and comorbidities. We also prospect future studies using integrative multiomics approaches to better understand host-microbiota-metabolites interactions in HIV infection, and facilitate integrative medicine utilizing the microbiota in HIV infection.
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Affiliation(s)
- Zheng Wang
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Qibin Qi
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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25
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Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, Berenjian A, Ghasemi Y. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods 2019; 8:E92. [PMID: 30857316 PMCID: PMC6463098 DOI: 10.3390/foods8030092] [Citation(s) in RCA: 701] [Impact Index Per Article: 116.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 03/04/2019] [Accepted: 03/05/2019] [Indexed: 12/20/2022] Open
Abstract
Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship with human overall health has been an area of increasing interest in recent years. They can feed the intestinal microbiota, and their degradation products are short-chain fatty acids that are released into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups of prebiotics with beneficial effects on human health. Since low quantities of fructo-oligosaccharides and galacto-oligosaccharides naturally exist in foods, scientists are attempting to produce prebiotics on an industrial scale. Considering the health benefits of prebiotics and their safety, as well as their production and storage advantages compared to probiotics, they seem to be fascinating candidates for promoting human health condition as a replacement or in association with probiotics. This review discusses different aspects of prebiotics, including their crucial role in human well-being.
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Affiliation(s)
- Dorna Davani-Davari
- Pharmaceutical Biotechnology Incubator, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
| | - Manica Negahdaripour
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
| | - Iman Karimzadeh
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
| | - Mostafa Seifan
- Faculty of Science and Engineering, University of Waikato, Hamilton 3216, New Zealand.
| | - Milad Mohkam
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
| | - Seyed Jalil Masoumi
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
| | - Aydin Berenjian
- Faculty of Science and Engineering, University of Waikato, Hamilton 3216, New Zealand.
| | - Younes Ghasemi
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz 71348, Iran.
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26
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Wang L, Wang E, Wang Y, Mines R, Xiang K, Sun Z, Zhou G, Chen KY, Rakhilin N, Chao S, Ye G, Wu Z, Yan H, Shen H, Everitt J, Bu P, Shen X. miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis. eLife 2018; 7:e39479. [PMID: 30543324 PMCID: PMC6314783 DOI: 10.7554/elife.39479] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 12/06/2018] [Indexed: 12/22/2022] Open
Abstract
Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the microRNA miR-34a acts as a central safeguard to protect the inflammatory stem cell niche and reparative regeneration. Although playing little role in regular homeostasis, miR-34a deficiency leads to colon tumorigenesis after Citrobacter rodentium infection. miR-34a targets both immune and epithelial cells to restrain inflammation-induced stem cell proliferation. miR-34a targets Interleukin six receptor (IL-6R) and Interleukin 23 receptor (IL-23R) to suppress T helper 17 (Th17) cell differentiation and expansion, targets chemokine CCL22 to hinder Th17 cell recruitment to the colon epithelium, and targets an orphan receptor Interleukin 17 receptor D (IL-17RD) to inhibit IL-17-induced stem cell proliferation. Our study highlights the importance of microRNAs in protecting the stem cell niche during inflammation despite their lack of function in regular tissue homeostasis.
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Affiliation(s)
- Lihua Wang
- Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in BiomacromoleculesInstitute of Biophysics, Chinese Academy of SciencesBeijingChina
- University of Chinese Academy of SciencesBeijingChina
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
| | - Ergang Wang
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
| | - Yi Wang
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
- Affiliated Hospital of Nanjing University of TCMNanjingChina
| | - Robert Mines
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
| | - Kun Xiang
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
| | - Zhiguo Sun
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
| | - Gaiting Zhou
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
| | - Kai-Yuan Chen
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
| | - Nikolai Rakhilin
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- School of Electrical and Computer EngineeringCornell UniversityNew yorkUnited States
| | - Shanshan Chao
- Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in BiomacromoleculesInstitute of Biophysics, Chinese Academy of SciencesBeijingChina
- University of Chinese Academy of SciencesBeijingChina
| | - Gaoqi Ye
- Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in BiomacromoleculesInstitute of Biophysics, Chinese Academy of SciencesBeijingChina
- University of Chinese Academy of SciencesBeijingChina
| | - Zhenzhen Wu
- Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in BiomacromoleculesInstitute of Biophysics, Chinese Academy of SciencesBeijingChina
- University of Chinese Academy of SciencesBeijingChina
| | - Huiwen Yan
- Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in BiomacromoleculesInstitute of Biophysics, Chinese Academy of SciencesBeijingChina
- University of Chinese Academy of SciencesBeijingChina
| | - Hong Shen
- Affiliated Hospital of Nanjing University of TCMNanjingChina
| | - Jeffrey Everitt
- Department of Pathology, Animal Pathology CoreDuke UniversityDurhamUnited States
| | - Pengcheng Bu
- Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, CAS Center for Excellence in BiomacromoleculesInstitute of Biophysics, Chinese Academy of SciencesBeijingChina
- University of Chinese Academy of SciencesBeijingChina
| | - Xiling Shen
- Center for Genomics and Computational BiologyDuke UniversityDurhamUnited States
- Department of Biomedical EngineeringDuke UniversityDurhamUnited States
- School of Electrical and Computer EngineeringCornell UniversityNew yorkUnited States
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27
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Gholizadeh P, Mahallei M, Pormohammad A, Varshochi M, Ganbarov K, Zeinalzadeh E, Yousefi B, Bastami M, Tanomand A, Mahmood SS, Yousefi M, Asgharzadeh M, Kafil HS. Microbial balance in the intestinal microbiota and its association with diabetes, obesity and allergic disease. Microb Pathog 2018; 127:48-55. [PMID: 30503960 DOI: 10.1016/j.micpath.2018.11.031] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/19/2018] [Accepted: 11/22/2018] [Indexed: 02/07/2023]
Abstract
Recent studies have been considered to symbiotic interactions of the human gastrointestinal microbiota and human lifestyle-related disorders. The human gastrointestinal microbiota continuously stimulates the immune system against opportunistic and pathogen bacteria from infancy. Changes in gastrointestinal microbiota have been associated with numbers of human diseases such as allergic diseases, autoimmune encephalitis, atherosclerosis, colorectal cancer, obesity, diabetes etc. In this review article, we evaluate studies on the roles of human gastrointestinal microbiota and interference pathogenicity in allergic diseases, obesity, and diabetes. Several studies indicated association between allergic diseases and changes in bacterial balance such as increased of Clostridium spp., some species of Bifidobacterium spp., or decreased of Bacteroidetes phylum and some species of Bifiobacterium spp. and production of specific short-chain fatty acids due to food type, delivery modes of infant, infant evolvement environment and time of getting bacteria at an early-life age. In addition, obesity and diabetes are associated with food type, production of short chain fatty acids undergo fermentation of the intestinal microbiota, metabolic endotoxemia, endocannabinoid system and properties of the immune system. Well-characterized underlying mechanisms may provide novel strategies for using prebiotic and probiotic to prevent and treatment of allergic diseases, obesity, diabetes, and other lifestyle-related disorders.
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Affiliation(s)
- Pourya Gholizadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Mahallei
- Children Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Pormohammad
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mojtaba Varshochi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Elham Zeinalzadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahman Yousefi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Milad Bastami
- Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Asghar Tanomand
- Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Suhad Saad Mahmood
- Department of Biotechnology, College of Science, University of Baghdad, Baghdad, Iraq
| | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Asgharzadeh
- Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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28
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Wang Z, Zolnik CP, Qiu Y, Usyk M, Wang T, Strickler HD, Isasi CR, Kaplan RC, Kurland IJ, Qi Q, Burk RD. Comparison of Fecal Collection Methods for Microbiome and Metabolomics Studies. Front Cell Infect Microbiol 2018; 8:301. [PMID: 30234027 PMCID: PMC6127643 DOI: 10.3389/fcimb.2018.00301] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 08/07/2018] [Indexed: 12/24/2022] Open
Abstract
Background: Integrated microbiome and metabolomics analyses hold the potential to reveal interactions between host and microbiota in relation to disease risks. However, there are few studies evaluating how field methods influence fecal microbiome characterization and metabolomics profiling. Methods: Five fecal collection methods [immediate freezing at -20°C without preservative, OMNIgene GUT, 95% ethanol, RNAlater, and Flinders Technology Associates (FTA) cards] were used to collect 40 fecal samples from eight healthy volunteers. We performed gut microbiota 16S rRNA sequencing, untargeted metabolomics profiling, and targeted metabolomics focusing on short chained fatty acids (SCFAs). Metrics included α-diversity and β-diversity as well as distributions of predominant phyla. To evaluate the concordance with the "gold standard" immediate freezing, the intraclass correlation coefficients (ICCs) for alternate fecal collection systems were calculated. Correlations between SCFAs and gut microbiota were also examined. Results: The FTA cards had the highest ICCs compared to the immediate freezing method for α-diversity indices (ICCs = 0.96, 0.96, 0.76 for Shannon index, Simpson's Index, Chao-1 Index, respectively), followed by OMNIgene GUT, RNAlater, and 95% ethanol. High ICCs (all >0.88) were observed for all methods for the β-diversity metric. For untargeted metabolomics, in comparison to immediate freezing which detected 621 metabolites at ≥75% detectability level, 95% ethanol showed the largest overlapping set of metabolites (n = 430; 69.2%), followed by FTA cards (n = 330; 53.1%) and OMNIgene GUT (n = 213; 34.3%). Both OMNIgene GUT (ICCs = 0.82, 0.93, 0.64) and FTA cards (ICCs = 0.87, 0.85, 0.54) had acceptable ICCs for the top three predominant SCFAs (butyric acid, propionic acid and acetic acid). Nominally significant correlations between bacterial genera and SCFAs (P < 0.05) were observed in fecal samples collected by different methods. Of note, a high correlation between the genus Blautia (known butyrate producer) and butyric acid was observed for both immediate freezing (r = 0.83) and FTA cards (r = 0.74). Conclusions: Four alternative fecal collection methods are generally comparable with immediate freezing, but there are differences in certain measures of the gut microbiome and fecal metabolome across methods. Choice of method depends on the research interests, simplicity of fecal collection procedures and ease of transportation to the lab, especially for large epidemiological studies.
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Affiliation(s)
- Zheng Wang
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Christine P. Zolnik
- Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, United States
- Department of Biology, Long Island University, Brooklyn, NY, United States
| | - Yunping Qiu
- Department of Medicine, Stable Isotope and Metabolomics Core Facility, Diabetes Center, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Mykhaylo Usyk
- Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Tao Wang
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Howard D. Strickler
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Carmen R. Isasi
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Robert C. Kaplan
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
| | - Irwin J. Kurland
- Department of Medicine, Stable Isotope and Metabolomics Core Facility, Diabetes Center, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Qibin Qi
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Robert D. Burk
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
- Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, United States
- Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, United States
- Obstetrics, Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, United States
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29
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Wassenaar TM. E. coli and colorectal cancer: a complex relationship that deserves a critical mindset. Crit Rev Microbiol 2018; 44:619-632. [DOI: 10.1080/1040841x.2018.1481013] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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30
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Gut microbiome of Moroccan colorectal cancer patients. Med Microbiol Immunol 2018; 207:211-225. [PMID: 29687353 PMCID: PMC6096775 DOI: 10.1007/s00430-018-0542-5] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 03/24/2018] [Indexed: 12/18/2022]
Abstract
Although colorectal cancer is the third leading cause of death in Morocco, there are no studies of the microbiome changes associated with the disease in the Moroccan population. The aim of our study was to compare the stool microbiome of Moroccan cancer patients with healthy individuals. We analyzed the microbiome composition of samples from 11 CRC patients and 12 healthy individuals by 16S rRNA amplicon sequencing. Principal coordinate analysis of samples revealed defined cancer versus healthy clusters. Our findings showed that cancer samples had higher proportions of Firmicutes (T = 50.5%; N = 28.4%; p = 0.04), specifically of Clostridia (T = 48.3%; N = 19.0%; p = 0.002), and Fusobacteria (T = 0.1%; N = 0.0%; p = 0.02), especially of Fusobacteriia (T = 0.1%; N = 0.0%; p = 0.02), while Bacteroidetes were enriched in healthy samples (T = 35.1%; N = 62.8%; p = 0.06), particularly the class Bacteroidia (T = 35.1%; N = 62.6%; p = 0.06). Porphyromonas, Clostridium, Ruminococcus, Selenomonas, and Fusobacterium were significantly overrepresented in diseased patients, similarly to other studies. Predicted functional information showed that bacterial motility proteins, flagellar assembly, and fatty acid biosynthesis metabolism were significantly overrepresented in cancer patients, while amino acid metabolism and glycan biosynthesis were overrepresented in controls. This suggests that involvement of these functional metagenomes is similar and relevant in the carcinogenesis process, independent of the origin of the samples. Results from this study allowed identification of bacterial taxa relevant to the Moroccan population and encourages larger studies to facilitate population-directed therapeutic approaches.
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32
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Chong J, Xia J. Computational Approaches for Integrative Analysis of the Metabolome and Microbiome. Metabolites 2017; 7:E62. [PMID: 29156542 PMCID: PMC5746742 DOI: 10.3390/metabo7040062] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 11/14/2017] [Accepted: 11/16/2017] [Indexed: 12/31/2022] Open
Abstract
The study of the microbiome, the totality of all microbes inhabiting the host or an environmental niche, has experienced exponential growth over the past few years. The microbiome contributes functional genes and metabolites, and is an important factor for maintaining health. In this context, metabolomics is increasingly applied to complement sequencing-based approaches (marker genes or shotgun metagenomics) to enable resolution of microbiome-conferred functionalities associated with health. However, analyzing the resulting multi-omics data remains a significant challenge in current microbiome studies. In this review, we provide an overview of different computational approaches that have been used in recent years for integrative analysis of metabolome and microbiome data, ranging from statistical correlation analysis to metabolic network-based modeling approaches. Throughout the process, we strive to present a unified conceptual framework for multi-omics integration and interpretation, as well as point out potential future directions.
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Affiliation(s)
- Jasmine Chong
- Institute of Parasitology, McGill University, Montreal, QC H3A 0G4, Canada.
| | - Jianguo Xia
- Institute of Parasitology, McGill University, Montreal, QC H3A 0G4, Canada.
- Department of Animal Science, McGill University, Montreal, QC H3A 0G4, Canada.
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33
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Abstract
The high affinity leukotriene B4 receptor, BLT1 mediates chemotaxis of diverse leukocyte subsets to the sites of infection or inflammation. Whereas the pathological functions of LTB4/BLT1 axis in allergy, autoimmunity and cardiovascular disorders are well established; its role in cancer is only beginning to emerge. In this review, we summarize recent findings on LTB4/BLT1 axis enabling distinct outcomes toward tumor progression. In a mouse lung tumor model promoted by silicosis-induced inflammation, genetic deletion of BLT1 attenuated neutrophilic inflammation and tumor promotion. In contrast, in a spontaneous model of intestinal tumorigenesis, absence of BLT1 led to defective mucosal host response, altered microbiota and bacteria dependent colon tumor progression. Furthermore, BLT1 mediated CD8+ T cell recruitment was shown to be essential for initiating anti-tumor immunity in number of xenograft models and is critical for effective PD1 based immunotherapy. BLT2 mediated chemotherapy resistance, tumor promotion and metastasis are also discussed. This new information points to a paradigm shift in our understanding of the LTB4 pathways in cancer.
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34
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Banna GL, Torino F, Marletta F, Santagati M, Salemi R, Cannarozzo E, Falzone L, Ferraù F, Libra M. Lactobacillus rhamnosus GG: An Overview to Explore the Rationale of Its Use in Cancer. Front Pharmacol 2017; 8:603. [PMID: 28919861 PMCID: PMC5585742 DOI: 10.3389/fphar.2017.00603] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 08/21/2017] [Indexed: 12/14/2022] Open
Abstract
Cancer is the second leading cause of death in the western world. In the era of precision medicine, a significant number of cancer patients can be cured with several anti-cancer therapeutic regimens. However, therapy failure may be caused by treatment side effects, such as diarrhea, especially occurring in patients with gastrointestinal or pelvic malignancies. In particular, diarrhea is one of the most frequent gastrointestinal toxicity during cancer treatment and it can result from nearly bot chemo- and radio-therapeutic strategies currently used. Diarrhea has a serious impact on patients’ quality of life and treatment dosing and schedule modification due to its severity can negatively influence treatment outcomes. In this context, probiotics may play an interesting role in several human diseases with an inflammatory bowel involvement and, among these, Lactobacillus rhamnosus GG (LGG) is one of the most characterized and utilized. In particular, LGG is able to reverse intestinal dysbiosis and moderate diarrhea. Moreover, preclinical studies have documented its effects in reducing chronic inflammation associated with cancer development. This review summarizes the preclinical results of LGG on cancer cells proliferation and tumor invasion as well as the potential role of LGG use in cancer patients for the prevention and management of diarrhea associated with cancer treatment. Overall, these encouraging data support further investigation on the use of LGG in stratified patients undergoing specific therapeutic protocols, including chemotherapy and pelvic radiotherapy, in order to reduce the development of severe diarrhea and thus improve the adherence to the therapy and patients’ quality of life.
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Affiliation(s)
| | - Francesco Torino
- Department of Systems Medicine, Chair of Medical Oncology, Tor Vergata University of RomeRome, Italy
| | | | - Maria Santagati
- Department of Biomedical and Biotechnological Sciences, Section of Microbiology, University of CataniaCatania, Italy
| | - Rossella Salemi
- Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of CataniaCatania, Italy
| | - Elisa Cannarozzo
- Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of CataniaCatania, Italy
| | - Luca Falzone
- Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of CataniaCatania, Italy
| | - Francesco Ferraù
- Division of Medical Oncology, San Vincenzo HospitalTaormina, Italy
| | - Massimo Libra
- Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of CataniaCatania, Italy
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Jala VR, Maturu P, Bodduluri SR, Krishnan E, Mathis S, Subbarao K, Wang M, Jenson AB, Proctor ML, Rouchka EC, Knight R, Haribabu B. Leukotriene B 4-receptor-1 mediated host response shapes gut microbiota and controls colon tumor progression. Oncoimmunology 2017; 6:e1361593. [PMID: 29209564 DOI: 10.1080/2162402x.2017.1361593] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Revised: 07/24/2017] [Accepted: 07/26/2017] [Indexed: 02/07/2023] Open
Abstract
Inflammation and infection are key promoters of colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in leukotriene B4 receptor1 (BLT1) are protected in inflammatory disease models of arthritis, asthma and atherosclerosis. In this study, we show that BLT1-/- mice when bred onto a spontaneous tumor (ApcMin/+) model displayed an increase in the rate of intestinal tumor development and mortality. A paradoxical increase in inflammation in the tumors from the BLT1-/-ApcMin/+ mice is coincidental with defective host response to infection. Germ-free BLT1-/-ApcMin/+ mice are free from colon tumors that reappeared upon fecal transplantation. Analysis of microbiota showed defective host response in BLT1-/- ApcMin/+ mice reshapes the gut microbiota to promote colon tumor development. The BLT1-/-MyD88-/- double deficient mice are susceptible to lethal neonatal infections. Broad-spectrum antibiotic treatment eliminated neonatal lethality in BLT1-/-MyD88-/- mice and the BLT1-/-MyD88-/-ApcMin+ mice are protected from colon tumor development. These results identify a novel interplay between the Toll-like receptor mediated microbial sensing mechanisms and BLT1-mediated host response in the control of colon tumor development.
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Affiliation(s)
- Venkatakrishna R Jala
- James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Paramahamsa Maturu
- James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Sobha R Bodduluri
- James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Elangovan Krishnan
- James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Steven Mathis
- James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Krishnaprasad Subbarao
- James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Min Wang
- James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Alfred B Jenson
- Department of Pathology, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Mary L Proctor
- Research Resources Center, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Eric C Rouchka
- Department of Computer Engineering & Computer Science, Speed School of Engineering, University of Louisville, Louisville, KY, USA
| | - Rob Knight
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Bodduluri Haribabu
- James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, USA
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Ramadass B, Rani BS, Pugazhendhi S, John K, Ramakrishna BS. Faecal microbiota of healthy adults in south India: Comparison of a tribal & a rural population. Indian J Med Res 2017; 145:237-246. [PMID: 28639601 PMCID: PMC5501057 DOI: 10.4103/ijmr.ijmr_639_14] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND & OBJECTIVES The relevance of the gut microbiota to human health is increasingly appreciated. The objective of this study was to compare the gut microbiota of a group of adult tribals with that of healthy adult villagers in Tamil Nadu, India. METHODS Faeces were collected from 10 healthy tribal adults (TAs) in the Jawadhi hills and from 10 healthy villagers [rural adults (RAs)] in Vellore district, Tamil Nadu. DNA was extracted, and 456 bp segments comprising hypervariable regions 3 and 4 of the 16S rRNA gene were amplified, barcoded and 454 sequenced. RESULTS Totally 227,710 good-quality reads were analyzed. TAs consumed a millets-based diet, ate pork every day, and did not consume milk or milk products. RAs consumed a rice-based diet with meat intake once a week. In both groups, Firmicutes was the most abundant phylum, followed by Proteobacteria, Bacteroidetes and Actinobacteria. The median Firmicutes-to-Bacteroidetes ratio was 34.0 in TA and 92.9 in RA groups. Actinobacteria were significantly low in TA, possibly due to non-consumption of milk. Clostridium constituted the most abundant genus in both groups, but was significantly more abundant in TAs than RAs, while Streptococcus was significantly more abundant in RA (P<0.05). Analyses of genetic distance revealed that the microbiota were distinctly different between TA and RA, and principal component analysis using 550 distinct taxonomically identifiable sequences revealed a clear separation of microbiota composition in the two groups. Phylogenetic analysis of major microbiota indicated clustering of microbial groups at different major branch points for TAs and RAs. INTERPRETATION & CONCLUSIONS Phylum Firmicutes and genus Clostridium constituted the bulk of the faecal microbiota, while significant differences in composition between the groups were probably due to differences in diet and lifestyle.
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Affiliation(s)
- Balamurugan Ramadass
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - B. Sandya Rani
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | | | - K.R. John
- Department of Community Health, Christian Medical College, Vellore, Chennai, India
- Institute of Gastroenterology, SRM Institutes for Medical Science, Chennai, India
| | - Balakrishnan S. Ramakrishna
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
- Institute of Gastroenterology, SRM Institutes for Medical Science, Chennai, India
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Corfield A. Eukaryotic protein glycosylation: a primer for histochemists and cell biologists. Histochem Cell Biol 2017; 147:119-147. [PMID: 28012131 PMCID: PMC5306191 DOI: 10.1007/s00418-016-1526-4] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2016] [Indexed: 12/21/2022]
Abstract
Proteins undergo co- and posttranslational modifications, and their glycosylation is the most frequent and structurally variegated type. Histochemically, the detection of glycan presence has first been performed by stains. The availability of carbohydrate-specific tools (lectins, monoclonal antibodies) has revolutionized glycophenotyping, allowing monitoring of distinct structures. The different types of protein glycosylation in Eukaryotes are described. Following this educational survey, examples where known biological function is related to the glycan structures carried by proteins are given. In particular, mucins and their glycosylation patterns are considered as instructive proof-of-principle case. The tissue and cellular location of glycoprotein biosynthesis and metabolism is reviewed, with attention to new findings in goblet cells. Finally, protein glycosylation in disease is documented, with selected examples, where aberrant glycan expression impacts on normal function to let disease pathology become manifest. The histological applications adopted in these studies are emphasized throughout the text.
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Affiliation(s)
- Anthony Corfield
- Mucin Research Group, School of Clinical Sciences, Bristol Royal Infirmary, University of Bristol, Bristol, BS2 8HW, UK.
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Borges-Canha M, Portela-Cidade JP, Dinis-Ribeiro M, Leite-Moreira AF, Pimentel-Nunes P. Role of colonic microbiota in colorectal carcinogenesis: a systematic review. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 107:659-71. [PMID: 26541655 DOI: 10.17235/reed.2015.3830/2015] [Citation(s) in RCA: 115] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND AIM The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile). Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. METHODS Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. RESULTS Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales), while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema). Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. CONCLUSION Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.
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Affiliation(s)
- Marta Borges-Canha
- Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Portugal
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Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine and Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine and Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Huang H, Krishnan HB, Pham Q, Yu LL, Wang TTY. Soy and Gut Microbiota: Interaction and Implication for Human Health. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2016; 64:8695-8709. [PMID: 27798832 DOI: 10.1021/acs.jafc.6b03725] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Soy (Glycine max) is a major commodity in the United States, and soy foods are gaining popularity due to their reported health-promoting effects. In the past two decades, soy and soy bioactive components have been studied for their health-promoting/disease-preventing activities and potential mechanisms of action. Recent studies have identified gut microbiota as an important component in the human body ecosystem and possibly a critical modulator of human health. Soy foods' interaction with the gut microbiota may critically influence many aspects of human development, physiology, immunity, and nutrition at different stages of life. This review summarizes current knowledge on the effects of soy foods and soy components on gut microbiota population and composition. It was found, although results vary in different studies, in general, both animal and human studies have shown that consumption of soy foods can increase the levels of bifidobacteria and lactobacilli and alter the ratio between Firmicutes and Bacteroidetes. These changes in microbiota are consistent with reported reductions in pathogenic bacteria populations in the gut, thereby lowering the risk of diseases and leading to beneficial effects on human health.
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Affiliation(s)
- Haiqiu Huang
- Diet, Genomics and Immunology Laboratory, U.S. Department of Agriculture-Agricultural Research Service , Beltsville, Maryland 20705, United States
| | - Hari B Krishnan
- Plant Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service, University of Missouri , Columbia, Missouri 65211, United States
| | - Quynhchi Pham
- Diet, Genomics and Immunology Laboratory, U.S. Department of Agriculture-Agricultural Research Service , Beltsville, Maryland 20705, United States
| | - Liangli Lucy Yu
- Department of Nutrition and Food Science, University of Maryland , College Park, Maryland 20742, United States
| | - Thomas T Y Wang
- Diet, Genomics and Immunology Laboratory, U.S. Department of Agriculture-Agricultural Research Service , Beltsville, Maryland 20705, United States
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Zhang M, Yang XJ. Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases. World J Gastroenterol 2016; 22:8905-8909. [PMID: 27833381 PMCID: PMC5083795 DOI: 10.3748/wjg.v22.i40.8905] [Citation(s) in RCA: 107] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Revised: 08/15/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.
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Saber A, Alipour B, Faghfoori Z, Yari Khosroushahi A. Cellular and molecular effects of yeast probiotics on cancer. Crit Rev Microbiol 2016; 43:96-115. [PMID: 27561003 DOI: 10.1080/1040841x.2016.1179622] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The cancer is one of the main causes of human deaths worldwide. The exact mechanisms of initiation and progression of malignancies are not clear yet, but there is a common agreement about the role of colonic microbiota in the etiology of different cancers. Probiotics have been examined for their anti-cancer effects, and different mechanisms have been suggested about their antitumor functions. Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. Generally safe yeasts have shown so many beneficial effects on human health. Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.
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Affiliation(s)
- Amir Saber
- a Biotechnology Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,b Student Research Committee, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,c Department of Biochemistry and Diet Therapy , Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran
| | - Beitollah Alipour
- c Department of Biochemistry and Diet Therapy , Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran.,d Nutrition Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences , Tabriz , Iran
| | - Zeinab Faghfoori
- e Faculty of Medicine, Semnan University of Medical Sciences , Semnan , Iran
| | - Ahmad Yari Khosroushahi
- f Drug Applied Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.,g Department of Pharmacognosy , Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran
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Saha P, Yeoh BS, Singh R, Chandrasekar B, Vemula PK, Haribabu B, Vijay-Kumar M, Jala VR. Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases. PLoS One 2016; 11:e0156811. [PMID: 27254317 PMCID: PMC4890745 DOI: 10.1371/journal.pone.0156811] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 05/19/2016] [Indexed: 12/15/2022] Open
Abstract
Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in acquiring limiting nutrient iron and thrive in the gut.
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Affiliation(s)
- Piu Saha
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America
| | - Beng San Yeoh
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America
| | - Rajbir Singh
- Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America
| | - Bhargavi Chandrasekar
- Institute for Stem Cell Biology and Regenerative Medicine (inStem), UAS-GKVK Campus, Bellary Road, Bangalore, Karnataka, India
| | - Praveen Kumar Vemula
- Institute for Stem Cell Biology and Regenerative Medicine (inStem), UAS-GKVK Campus, Bellary Road, Bangalore, Karnataka, India
- Ramalingaswami ReEntry Fellow, Dept. of Biotechnology, Govt. of India
| | - Bodduluri Haribabu
- Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America
| | - Matam Vijay-Kumar
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America
- Department of Medicine, The Pennsylvania State University Medical Center, Hershey, Pennsylvania, United States of America
- * E-mail: (MVK); (VRJ)
| | - Venkatakrishna R. Jala
- Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America
- * E-mail: (MVK); (VRJ)
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Nistal E, Fernández-Fernández N, Vivas S, Olcoz JL. Factors Determining Colorectal Cancer: The Role of the Intestinal Microbiota. Front Oncol 2015; 5:220. [PMID: 26528432 PMCID: PMC4601259 DOI: 10.3389/fonc.2015.00220] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Accepted: 09/24/2015] [Indexed: 12/26/2022] Open
Abstract
The gastrointestinal tract, in particular the colon, holds a complex community of microorganisms, which are essential for maintaining homeostasis. However, in recent years, many studies have implicated microbiota in the development of colorectal cancer (CRC), with this disease considered a major cause of death in the western world. The mechanisms underlying bacterial contribution in its development are complex and are not yet fully understood. However, there is increasing evidence showing a connection between intestinal microbiota and CRC. Intestinal microorganisms cause the onset and progression of CRC using different mechanisms, such as the induction of a chronic inflammation state, the biosynthesis of genotoxins that interfere with cell cycle regulation, the production of toxic metabolites, or heterocyclic amine activation of pro-diet carcinogenic compounds. Despite these advances, additional studies in humans and animal models will further decipher the relationship between microbiota and CRC, and aid in developing alternate therapies based on microbiota manipulation.
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Affiliation(s)
- Esther Nistal
- Instituto de Biomedicina (IBIOMED), Universidad de León , León , Spain
| | | | - Santiago Vivas
- Instituto de Biomedicina (IBIOMED), Universidad de León , León , Spain ; Gastroenterología, Hospital Universitario de León , León , Spain
| | - José Luis Olcoz
- Gastroenterología, Hospital Universitario de León , León , Spain
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Bertuzzi M, Marelli C, Bagnati R, Colombi A, Fanelli R, Saieva C, Ceroti M, Bendinelli B, Caini S, Airoldi L, Palli D. Plasma clusterin as a candidate pre-diagnosis marker of colorectal cancer risk in the Florence cohort of the European Prospective Investigation into Cancer and Nutrition: a pilot study. BMC Cancer 2015; 15:56. [PMID: 25884309 PMCID: PMC4334607 DOI: 10.1186/s12885-015-1058-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 01/29/2015] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Colorectal cancer is one of the major causes of cancer mortality world-wide. Prevention would improve if at-risk subjects could be identified. The aim of this study was to characterise plasma protein biomarkers associated with the risk of colorectal cancer in samples collected prospectively, before the disease diagnosis. METHODS After an exploratory study on the comprehensive plasma proteome analysis by liquid chromatography-tandem mass spectrometry from ten colorectal cancer cases enrolled at diagnosis, and ten matched controls (Phase 1), a similar preliminary study was performed on prospective plasma samples from ten colorectal cancer cases, enrolled years before disease development, and ten matched controls identified in a nested case-control study within the Florence cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study (Phase 2); in Phase 3 the validation of the candidate biomarkers by targeted proteomics on 48 colorectal cancer cases and 48 matched controls from the Florence-EPIC cohort, and the evaluation of the disease risk were performed. RESULTS Systems biology tools indicated that both in the Phase 1 and Phase 2 studies circulating protein levels differing in cases more than 1.5 times from controls, were involved in inflammation and/or immune response. Eight proteins including apolipoprotein C-II, complement C4-B, complement component C9, clusterin, alpha-2-HS-glycoprotein, mannan-binding lectin serine-protease, mannose-binding protein C, and N-acetylmuramoyl-L-alanine amidase were selected as promising candidate biomarkers. Targeted proteomics of the selected proteins in the EPIC samples showed significantly higher clusterin levels in cases than controls, but only in men (mean ± SD, 1.98 ± 0.46 and 1.61 ± 0.43 nmol/mL respectively, Mann-Whitney U, two-tailed P = 0.0173). The remaining proteins were unchanged. Using multivariate logistic models a significant positive association emerged for clusterin, with an 80% increase in the colorectal cancer risk with protein's unit increase, but only in men. CONCLUSIONS The results show that plasma proteins can be altered years before colorectal cancer detection. The high circulating clusterin in pre-diagnostic samples suggests this biomarker can improve the identification of people at risk of colorectal cancer and might help in designing preventive interventions.
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Affiliation(s)
- Michela Bertuzzi
- Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156, Milano, Italy.
| | - Cristina Marelli
- Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156, Milano, Italy.
| | - Renzo Bagnati
- Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156, Milano, Italy.
| | - Alessandro Colombi
- Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156, Milano, Italy.
| | - Roberto Fanelli
- Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156, Milano, Italy.
| | - Calogero Saieva
- Molecular and Nutritional Epidemiology Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy.
| | - Marco Ceroti
- Molecular and Nutritional Epidemiology Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy.
| | - Benedetta Bendinelli
- Molecular and Nutritional Epidemiology Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy.
| | - Saverio Caini
- Molecular and Nutritional Epidemiology Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy.
| | - Luisa Airoldi
- Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156, Milano, Italy.
| | - Domenico Palli
- Molecular and Nutritional Epidemiology Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy.
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Mira-Pascual L, Cabrera-Rubio R, Ocon S, Costales P, Parra A, Suarez A, Moris F, Rodrigo L, Mira A, Collado MC. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol 2015; 50:167-79. [PMID: 24811328 DOI: 10.1007/s00535-014-0963-x] [Citation(s) in RCA: 187] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Accepted: 04/11/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Epidemiological studies demonstrate a link between gastrointestinal cancers and environmental factors such as diet. It has been suggested that environmental cancer risk is determined by the interaction between diet and microbes. Thus, the purpose of this study was to examine the hypothesis that microbiota composition during colorectal cancer (CRC) progression might differ depending on the stage of the disease. METHODS A total of 28 age-matched and sex-matched subjects, seven with CRC adenocarcinoma, 11 with tubular adenomas and ten healthy subjects with intact colon, were included into the study. Microbiomes from mucosal and fecal samples were analyzed with 16S ribosomal RNA gene pyrosequencing, together with quantitative PCR of specific bacteria and archaea. RESULTS The principal coordinates analysis clearly separated healthy tissue samples from polyps and tumors, supporting the presence of specific bacterial consortia that are associated with affected sites and that can serve as potential biomarkers of CRC progression. A higher presence of Fusobacterium nucleatum and Enterobacteriaceae was found by qPCR in samples from CRC compared to healthy controls. We observed a correlation between CRC process development and levels of Methanobacteriales (R = 0.537, P = 0.007) and Methanobrevibacterium (R = 0.574, P = 0.03) in fecal samples. CONCLUSION Differences in microbial and archaeal composition between mucosal samples from healthy and disease tissues were observed in tubular adenoma and adenocarcinoma. In addition, microbiota from mucosal samples represented the underlying dysbiosis, whereas fecal samples seem not to be appropriate to detect shifts in microbial composition. CRC risk is influenced by microbial composition, showing differences according to disease progression step and tumor severity.
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Affiliation(s)
- L Mira-Pascual
- Department of Biotechnology, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Av. Agustin Escardino 7, 49860, Paterna, Valencia, Spain
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Nyangale EP, Farmer S, Keller D, Chernoff D, Gibson GR. Effect of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation of Bacillus coagulans GBI-30, 6086. Anaerobe 2014; 30:75-81. [DOI: 10.1016/j.anaerobe.2014.09.002] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 09/01/2014] [Accepted: 09/03/2014] [Indexed: 12/16/2022]
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Abstract
Multigenic disease development is dependent on both missing and overactivated pathways, just as the homeostasis of our body systems is the product of many complex, redundant mechanisms. The goal of finding a common factor in the disease pathogenesis is difficult, as genetic and pathophysiological data are still incomplete, and the individual variability is enormous. Nevertheless, the examination of the role of human microbiota in illnesses using animal models of human diseases reared in defined (gnotobiotic) conditions could allow insight into the unusual complexity of the mechanisms involved in the initiation and maintenance of chronic diseases, including cancer. Although the most important findings in this fascinating field are still to come, a hypothesis, which is more than speculative, can be made, as it is clear that our bacterial companions affect our fates more than previously assumed.
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Food Omics Validation: Towards Understanding Key Features for Gut Microbiota, Probiotics and Human Health. FOOD ANAL METHOD 2014. [DOI: 10.1007/s12161-014-9923-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Centanni M, Turroni S, Rampelli S, Biagi E, Quercia S, Consolandi C, Severgnini M, Brigidi P, Candela M. Bifidobacterium animalisssp.lactisBI07 modulates the tumor necrosis factor alpha-dependent imbalances of the enterocyte-associated intestinal microbiota fraction. FEMS Microbiol Lett 2014; 357:157-63. [DOI: 10.1111/1574-6968.12515] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 06/06/2014] [Accepted: 06/18/2014] [Indexed: 12/12/2022] Open
Affiliation(s)
- Manuela Centanni
- Department of Pharmacy and Biotechnology; University of Bologna; Bologna Italy
| | - Silvia Turroni
- Department of Pharmacy and Biotechnology; University of Bologna; Bologna Italy
| | - Simone Rampelli
- Department of Pharmacy and Biotechnology; University of Bologna; Bologna Italy
| | - Elena Biagi
- Department of Pharmacy and Biotechnology; University of Bologna; Bologna Italy
| | - Sara Quercia
- Department of Pharmacy and Biotechnology; University of Bologna; Bologna Italy
| | - Clarissa Consolandi
- Institute of Biomedical Technologies - Italian National Research Council; Milan Italy
| | - Marco Severgnini
- Institute of Biomedical Technologies - Italian National Research Council; Milan Italy
| | - Patrizia Brigidi
- Department of Pharmacy and Biotechnology; University of Bologna; Bologna Italy
| | - Marco Candela
- Department of Pharmacy and Biotechnology; University of Bologna; Bologna Italy
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