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1
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Napolitano M, Covasa M. Microbiota Transplant in the Treatment of Obesity and Diabetes: Current and Future Perspectives. Front Microbiol 2020; 11:590370. [PMID: 33304339 PMCID: PMC7693552 DOI: 10.3389/fmicb.2020.590370] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 10/23/2020] [Indexed: 12/15/2022] Open
Abstract
A wealth of evidence has revealed the critical role of the gut microbiota in health and disease. Many chronic diseases have been associated with gut microbiota imbalance in its composition, diversity and functional capacity. Several types of interventions have been shown to correct microbiota imbalance and restore the beneficial metabolic outcomes of a normal microbiota. Among them, fecal microbiota transplantation (FMT) is an emergent, promising technology employed to improve clinical outcomes of various pathological conditions through modifications in the gut microbiota composition. FMT has been used successfully as a treatment option in recurrent Clostridium difficile infection, a condition characterized by severe gut microbiota dysbiosis. However, the potential usage of FMT in other microbiota-associated conditions different from C. difficile such as metabolic syndrome or obesity that are also marked by gut dysbiosis is still under investigation. Furthermore, the contribution of the gut microbiota as a cause or consequence in metabolic disease is still largely debated. This review provides critical information on the methodological approaches of FMT and its technological innovation in clinical applications. This review sheds light on the current findings and gaps in our understanding of how FMT can be used as a future biotherapeutic to restore microbial homeostasis in amelioration of obesity and diabetes.
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Affiliation(s)
- Michael Napolitano
- Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA, United States
| | - Mihai Covasa
- Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA, United States.,Department of Health and Human Development, Stefan Cel Mare University of Suceava, Suceava, Romania
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2
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Leung PC, Cheng KF. Fecal microbiota transplantation: Historical review and current perspective. World J Meta-Anal 2019; 7:423-427. [DOI: 10.13105/wjma.v7.i9.423] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/21/2019] [Accepted: 10/25/2019] [Indexed: 02/06/2023] Open
Abstract
There is a growing interest in the use of fecal transplantation for chronic intestinal conditions. We aim to review the methodology and safety of fecal microbiota transplantation and the evidence to support its use in treating a variety of diseases. We reviewed the history of fecal transplantation in China and found that there were varieties of fecal material used in ancient China. The first written record on fecal treatment was found in an ancient tomb in Middle China. This paper explores the historical and current perspectives of fecal microbiota transplantation. The ancient fecal transplantations did not have any background support from life science. In those ancient days, short of knowledge about bacteria, clinicians were aiming at a change of intestinal environment. Today, we aim at a change of the intestinal microbiome.
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Affiliation(s)
- Ping-Chung Leung
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants (The Chinese University of Hong Kong), Hong Kong, China
| | - King-Fai Cheng
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China
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3
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Kahn SA, Rubin DT. When Subjects Violate the Research Covenant: Lessons Learned from a Failed Clinical Trial of Fecal Microbiota Transplantation. Am J Gastroenterol 2016; 111:1508-1510. [PMID: 27166127 DOI: 10.1038/ajg.2016.153] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Stacy A Kahn
- Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, Illinois, USA.,The MacLean Center for Clinical Medical Ethics, The University of Chicago Medicine, Chicago, Illinois, USA.,Section of Pediatric Gastroenterology, Hepatology, & Nutrition, The University of Chicago Medicine, Chicago, Illinois, USA
| | - David T Rubin
- Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, Illinois, USA.,The MacLean Center for Clinical Medical Ethics, The University of Chicago Medicine, Chicago, Illinois, USA
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4
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Houben T, Brandsma E, Walenbergh SMA, Hofker MH, Shiri-Sverdlov R. Oxidized LDL at the crossroads of immunity in non-alcoholic steatohepatitis. Biochim Biophys Acta Mol Cell Biol Lipids 2016; 1862:416-429. [PMID: 27472963 DOI: 10.1016/j.bbalip.2016.07.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 07/01/2016] [Accepted: 07/21/2016] [Indexed: 02/08/2023]
Abstract
Non-alcoholic steatohepatitis (NASH) is viewed as the hepatic manifestation of the metabolic syndrome and is a condition hallmarked by lipid accumulation in the liver (steatosis) along with inflammation (hepatitis). Currently, the etiology and mechanisms leading to obesity-induced hepatic inflammation are not clear and, as a consequence, strategies to diagnose or treat NASH in an accurate manner do not exist. In the current review, we put forward the concept of oxidized lipids as a significant risk factor for NASH. We will focus on the contribution of the different types of oxidized lipids as part of the oxidized low-density lipoprotein (oxLDL) to the hepatic inflammatory response. Furthermore, we will elaborate on the underlying mechanisms linking oxLDL to inflammatory responses in the liver and on how these cascades can be used as therapeutic targets to combat NASH. This article is part of a Special Issue entitled: Lipid modification and lipid peroxidation products in innate immunity and inflammation edited by Christoph J. Binder.
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Affiliation(s)
- T Houben
- Department of Molecular Genetics, Maastricht University, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht, the Netherlands
| | - E Brandsma
- Molecular Genetics Section, Department of Pediatrics, University Medical Center Groningen, University of Groningen, the Netherlands
| | - S M A Walenbergh
- Department of Molecular Genetics, Maastricht University, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht, the Netherlands
| | - M H Hofker
- Molecular Genetics Section, Department of Pediatrics, University Medical Center Groningen, University of Groningen, the Netherlands
| | - R Shiri-Sverdlov
- Department of Molecular Genetics, Maastricht University, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht, the Netherlands.
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5
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Aguirre M, Venema K. The art of targeting gut microbiota for tackling human obesity. GENES AND NUTRITION 2015; 10:472. [PMID: 25991499 DOI: 10.1007/s12263-015-0472-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 05/11/2015] [Indexed: 02/07/2023]
Abstract
Recently, a great deal of interest has been expressed regarding strategies to tackle worldwide obesity because of its accelerated wide spread accompanied with numerous negative effects on health and high costs. Obesity has been traditionally associated with an imbalance in energy consumed when compared to energy expenditure. However, growing evidence suggests a less simplistic event in which gut microbiota plays a key role. Obesity, in terms of microbiota, is a complicated disequilibrium that presents many unclear complications. Despite this, there is special interest in characterizing compositionally and functionally the obese gut microbiota with the help of in vitro, animal and human studies. Considering the gut microbiota as a factor contributing to human obesity represents a tool of great therapeutic potential. This paper reviews the use of antimicrobials, probiotics, fecal microbial therapy, prebiotics and diet to manipulate obesity through the human gut microbiota and reveals inconsistencies and implications for future study.
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Affiliation(s)
- Marisol Aguirre
- Top Institute of Food and Nutrition, PO Box 557, 6700 AA, Wageningen, The Netherlands
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6
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Nanki K, Naganuma M, Mizuno S, Matsuoka K, Kanai T. Bacteriotherapy reintroduces “old friends” in IBD. Inflamm Regen 2015. [DOI: 10.2492/inflammregen.35.122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Kosaku Nanki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Makoto Naganuma
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Shinta Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Central Hospital, Tokyo, Japan
| | - Katsuyoshi Matsuoka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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7
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Baty V, Mougin B, Dekeuwer C, Carret G. Gut Health in the era of the human gut microbiota: from metaphor to biovalue. MEDICINE, HEALTH CARE, AND PHILOSOPHY 2014; 17:579-597. [PMID: 24610296 DOI: 10.1007/s11019-014-9552-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
The human intestinal ecosystem, previously called the gut microflora is now known as the Human Gut Microbiota (HGM). Microbiome research has emphasized the potential role of this ecosystem in human homeostasis, offering unexpected opportunities in therapeutics, far beyond digestive diseases. It has also highlighted ethical, social and commercial concerns related to the gut microbiota. As diet factors are accepted to be the major regulator of the gut microbiota, the modulation of its composition, either by antibiotics or by food intake, should be regarded as a fascinating tool for improving the human health. Scientists, the food industry, consumers and policymakers alike are involved in this new field of nutrition. Defining how knowledge about the HGM is being translated into public perception has never been addressed before. This raises the question of metaphors associated with the HGM, and how they could be used to improve public understanding, and to influence individual decision-making on healthcare policy. This article suggests that a meeting of stakeholders from the social sciences, basic research and the food industry, taking an epistemological approach to the HGM, is needed to foster close, innovative partnerships that will help shape public perception and enable novel behavioural interventions that would benefit public health.
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Affiliation(s)
- Vincent Baty
- Service de Gastroentérologie, Clinique Mutualiste, 107 rue Trarieux, 69003, Lyon, France,
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Wang ZK, Yang YS, Chen Y, Yuan J, Sun G, Peng LH. Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease. World J Gastroenterol 2014; 20:14805-14820. [PMID: 25356041 PMCID: PMC4209544 DOI: 10.3748/wjg.v20.i40.14805] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2014] [Revised: 06/16/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.
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9
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Cammarota G, Ianiro G, Bibbò S, Gasbarrini A. Gut microbiota modulation: probiotics, antibiotics or fecal microbiota transplantation? Intern Emerg Med 2014; 9:365-73. [PMID: 24664520 DOI: 10.1007/s11739-014-1069-4] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Accepted: 03/10/2014] [Indexed: 12/11/2022]
Abstract
Gut microbiota is known to have a relevant role in our health, and is also related to both gastrointestinal and extradigestive diseases. Therefore, restoring the alteration of gut microbiota represents an outstanding clinical target for the treatment of gut microbiota-related diseases. The modulation of gut microbiota is perhaps an ancestral, innate concept for human beings. At this time, the restoration of gut microbiota impairment is a well-established concept in mainstream medicine, and several therapeutic approaches have been developed in this regard. Antibiotics, prebiotics and probiotics are the best known and commercially available options to overcome gastrointestinal dysbiosis. Fecal microbiota transplantation is an old procedure that has recently become popular again. It has shown a clear effectiveness in the treatment of C. difficile infection, and now represents a cutting-edge option for the restoration of gut microbiota. Nevertheless, such weapons should be used with caution. Antibiotics can indeed harm and alter gut microbiota composition. Probiotics, instead, are not at all the same thing, and thinking in terms of different strains is probably the only way to improve clinical outcomes. Moreover, fecal microbiota transplantation has shown promising results, but stronger proofs are needed. Considerable efforts are needed to increase our knowledge in the field of gut microbiota, especially with regard to the future use in its modulation for therapeutic purposes.
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10
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Kellermayer R. Prospects and challenges for intestinal microbiome therapy in pediatric gastrointestinal disorders. World J Gastrointest Pathophysiol 2013; 4:91-93. [PMID: 24244876 PMCID: PMC3829459 DOI: 10.4291/wjgp.v4.i4.91] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 07/23/2013] [Accepted: 08/09/2013] [Indexed: 02/06/2023] Open
Abstract
Fecal microbiome (microbiota) transplantation is an emerging treatment not only for refractory/recurrent Clostridium difficile infections and chronic gastrointestinal diseases, but also for metabolic syndrome, and even possibly for neurological disorders. This non-conventional therapy has been perhaps more appropriately designated as fecal bacteriotherapy (FB) as well. The employment of FB is spreading into pediatric gastroenterology. This focused review highlights the pediatric applications of FB and discusses hypotheses for its mechanism of action. We propose that intestinal microbiome therapy may be a more appropriate term for FB, which integrates its potential future applications.
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11
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Smits LP, Bouter KEC, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology 2013; 145:946-53. [PMID: 24018052 DOI: 10.1053/j.gastro.2013.08.058] [Citation(s) in RCA: 468] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Revised: 08/23/2013] [Accepted: 08/26/2013] [Indexed: 02/08/2023]
Abstract
There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal conditions that were not previously considered to be associated with the intestinal microbiota. Although it is not clear if changes in the microbiota cause these conditions, we review the most current and best methods for performing fecal microbiota transplantation and summarize clinical observations that have implicated the intestinal microbiota in various diseases. We also discuss case reports of fecal microbiota transplantations for different disorders, including Clostridium difficile infection, irritable bowel syndrome, inflammatory bowel diseases, insulin resistance, multiple sclerosis, and idiopathic thrombocytopenic purpura. There has been increasing focus on the interaction between the intestinal microbiome, obesity, and cardiometabolic diseases, and we explore these relationships and the potential roles of different microbial strains. We might someday be able to mine for intestinal bacterial strains that can be used in the diagnosis or treatment of these diseases.
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Affiliation(s)
- Loek P Smits
- Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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12
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13
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Gens KD, Elshaboury RH, Holt JS. Fecal microbiota transplantation and emerging treatments for Clostridium difficile infection. J Pharm Pract 2013; 26:498-505. [PMID: 23966282 DOI: 10.1177/0897190013499527] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Due to the increased incidence and recurrence of Clostridium difficile infection, health care providers are seeking new and alternative treatments to the standard antibiotic therapy. The objective of this article is to present a review on the background, microbiologic efficacy, clinical efficacy, and safety of fecal microbiota transplantation and to provide an overview of emerging treatment options currently under investigation. Emerging treatment options discussed include the use of monoclonal antibodies directed against toxins A and B, C difficile vaccination, and transplantation of nontoxigenic C difficile strains.
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Affiliation(s)
- Krista D Gens
- Department of Pharmacy, North Memorial Medical Center, Robbinsdale, MN, USA
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14
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Suwantarat N, Bobak DA. Fecal Bacteriotherapy for Recurrent Clostridium difficile Infection: What's Old Is New Again? Curr Infect Dis Rep 2013; 15:101-3. [PMID: 23549617 DOI: 10.1007/s11908-013-0314-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In recent years, effective management of recurrent Clostridium difficile infection (CDI) has emerged as an important issue for those clinicians who treat patients with CDI. In addition to antibiotic-based therapies, including alternating use, chaser, and tapering protocols, interest has increased in the potential utility of a variety of nonantibiotic forms of adjunctive therapy. Among these alternative forms of treatment, the concept of transferring extracts of a stool from donors to patients with CDI has been met with great interest among researchers, clinicians, and patients alike. Fecal bacteriotherapy, or so-called fecal microbiota transplantation, for therapy of CDI is a procedure that dates back to the 1950s. Recently, however, a variety of studies have garnered attention in the lay press, in addition to the standard scientific-reporting community. Although no well-controlled trials have been published as yet and the details of the procedures used have varied widely between institutions, the available evidence suggests that for selected patients, fecal bacteriotherapy appears to be generally safe and effective. Concerns about true efficacy and the theoretical potential for infectious complications have prevented widespread adoption of this concept as standard therapy, but its use in academic and community practices is on the rise.
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Affiliation(s)
- Nuntra Suwantarat
- Division of Infectious Diseases and HIV Medicine, Case School of Medicine, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106, USA,
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15
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Vrieze A, de Groot PF, Kootte RS, Knaapen M, van Nood E, Nieuwdorp M. Fecal transplant: a safe and sustainable clinical therapy for restoring intestinal microbial balance in human disease? Best Pract Res Clin Gastroenterol 2013; 27:127-37. [PMID: 23768558 DOI: 10.1016/j.bpg.2013.03.003] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Revised: 03/02/2013] [Accepted: 03/14/2013] [Indexed: 02/07/2023]
Abstract
Recent studies have suggested an association between intestinal microbiota composition and human disease, however causality remains to be proven. With hindsight, the application of fecal transplantation (FMT) does indeed suggest a causal relation between interfering with gut microbiota composition and a resultant cure of several disease states. In this review, we aim to show the available evidence regarding the involvement of intestinal microbiota and human (autoimmune) disease. Moreover, we refer to (mostly case report) studies showing beneficial or adverse effects of fecal transplantation on clinical outcomes in some of these disease states. If these findings can be substantiated in larger randomized controlled double blind trials also implementing gut microbiota composition before and after intervention, fecal transplantation might provide us with novel insights into causally related intestinal microbiota, that might be serve as future diagnostic and treatment targets in human disease.
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Affiliation(s)
- A Vrieze
- Department of Internal Medicine, AMC, University of Amsterdam, The Netherlands
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Grivennikov SI. Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol 2012; 35:229-44. [PMID: 23161445 DOI: 10.1007/s00281-012-0352-6] [Citation(s) in RCA: 407] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Accepted: 09/27/2012] [Indexed: 12/12/2022]
Abstract
Connection between inflammation and cancer is a rapidly developing field. Epidemiological data suggests that inflammation along with distinct arms of host immune system plays a very important role in the development and progression of many different cancers. Inflammatory bowel disease (IBD) is an important risk factor for the development of colon cancer, namely, colitis-associated cancer (CAC). The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and may differ between CAC and other forms of colorectal cancer. Recent work has shed light on the role of distinct immune cells, cytokines, and other immune mediators in virtually all of the steps of colonic tumorigenesis, including tumor initiation and promotion as well as progression and metastasis. The close proximity of colonic tumors to the myriad of intestinal microbes, as well as instrumental role of microbiota in IBD, introduces microbes as new players capable of triggering inflammation and possibly promoting tumorigenesis. Various mechanisms of CAC tumorigenesis as well as new possible hints for the future approaches for prevention and therapy are discussed in this review.
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Affiliation(s)
- Sergei I Grivennikov
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
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