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Du L, Ding X, Tian Y, Chen J, Li W. Effect of anthocyanins on metabolic syndrome through interacting with gut microbiota. Pharmacol Res 2024; 210:107511. [PMID: 39577753 DOI: 10.1016/j.phrs.2024.107511] [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: 08/18/2024] [Revised: 10/22/2024] [Accepted: 11/16/2024] [Indexed: 11/24/2024]
Abstract
Metabolic syndrome, as a complex pathological condition, is caused by a series of pathogenic factors and has become a global public health challenge. Anthocyanins, a natural water-soluble flavonoid pigment, have attracted much attention due to their antioxidant, anti-inflammatory, and anticancer biological activities. After ingestion, a majority of anthocyanins is not directly absorbed but rather reaches the colon. Hence, the exertion of their biological benefits is closely intertwined with the role played by gut microbiota. In this review, we introduce the pathogenesis and intervention methods of metabolic syndrome, as well as the interaction between anthocyanins and gut microbiota. We also discuss the therapeutic potential of anthocyanins through gut microbiota in addressing a range of metabolic syndrome conditions, including obesity, type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver disease, inflammatory bowel disease, polycystic ovary syndrome, osteoporosis, and cancer.
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Affiliation(s)
- Lanlan Du
- State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China, College of Forestry and Grassland, Nanjing Forestry University, Nanjing 210037, China
| | - Xiaoqin Ding
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Yuwen Tian
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Jian Chen
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
| | - Weilin Li
- State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China, College of Forestry and Grassland, Nanjing Forestry University, Nanjing 210037, China.
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2
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Karimi M, Shirsalimi N, Hashempour Z, Salehi Omran H, Sedighi E, Beigi F, Mortezazadeh M. Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: a comprehensive literature review. Front Immunol 2024; 15:1439176. [PMID: 39391303 PMCID: PMC11464302 DOI: 10.3389/fimmu.2024.1439176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 09/09/2024] [Indexed: 10/12/2024] Open
Abstract
The human gastrointestinal (GI) tract microbiome is a complex and all-encompassing ecological system of trillions of microorganisms. It plays a vital role in digestion, disease prevention, and overall health. When this delicate balance is disrupted, it can lead to various health issues. Fecal microbiota transplantation (FMT) is an emerging therapeutic intervention used as an adjuvant therapy for many diseases, particularly those with dysbiosis as their underlying cause. Its goal is to restore this balance by transferring fecal material from healthy donors to the recipients. FMT has an impressive reported cure rate between 80% and 90% and has become a favored treatment for many diseases. While FMT may have generally mild to moderate transient adverse effects, rare severe complications underscore the importance of rigorous donor screening and standardized administration. FMT has enormous potential as a practical therapeutic approach; however, additional research is required to further determine its potential for clinical utilization, as well as its safety and efficiency in different patient populations. This comprehensive literature review offers increased confidence in the safety and effectiveness of FMT for several diseases affecting the intestines and other systems, including diabetes, obesity, inflammatory and autoimmune illness, and other conditions.
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Affiliation(s)
- Mehdi Karimi
- Bogomolets National Medical University (NMU), Kyiv, Ukraine
| | - Niyousha Shirsalimi
- Faculty of Medicine, Hamadan University of Medical Science (UMSHA), Hamadan, Iran
| | - Zahra Hashempour
- School of Medicine, Shiraz University of Medical Sciences (SUMS), Shiraz, Iran
| | - Hossein Salehi Omran
- School of Medicine, Shahid Beheshti University of Medical Sciences (SBMUS), Tehran, Iran
| | - Eshagh Sedighi
- Department of Veterinary Medicine, Islamic Azad University Branch of Urmia, Urmia, Iran
| | - Farzan Beigi
- Students Research Committee, Arak University of Medical Sciences, Arak, Iran
| | - Masoud Mortezazadeh
- Department of Internal Medicine, Sina Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
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Oliva-Hemker M, Kahn SA, Steinbach WJ. Fecal Microbiota Transplantation: Information for the Pediatrician. Pediatrics 2023; 152:e2023062922. [PMID: 37981872 DOI: 10.1542/peds.2023-062922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/25/2023] [Indexed: 11/21/2023] Open
Abstract
Fecal microbiota transplantation (FMT) involves the delivery of an entire microbial community from a healthy donor to a recipient with the intention of ameliorating or curing a specific disease. Current evidence strongly supports a role for FMT in the treatment of Clostridiodes difficile infection, with cure rates of approximately 80% to 90%. This success has led to increasing attention for FMT as a potential therapeutic intervention for other conditions associated with disturbances of the intestinal microbiome, including inflammatory bowel diseases, autism spectrum disorder, and obesity. This clinical report endorses the joint society statement by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition and is meant to provide the general pediatrician with a broad overview to enable appropriate guidance to families seeking FMT as treatment of a child's condition.
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Affiliation(s)
- Maria Oliva-Hemker
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Stacy A Kahn
- FMT and Microbial Therapeutics Program, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Cambridge, Massachusetts
| | - William J Steinbach
- Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's, Fayetteville, Arkansas
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Zhao Q, Chen Y, Huang W, Zhou H, Zhang W. Drug-microbiota interactions: an emerging priority for precision medicine. Signal Transduct Target Ther 2023; 8:386. [PMID: 37806986 PMCID: PMC10560686 DOI: 10.1038/s41392-023-01619-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 07/20/2023] [Accepted: 08/24/2023] [Indexed: 10/10/2023] Open
Abstract
Individual variability in drug response (IVDR) can be a major cause of adverse drug reactions (ADRs) and prolonged therapy, resulting in a substantial health and economic burden. Despite extensive research in pharmacogenomics regarding the impact of individual genetic background on pharmacokinetics (PK) and pharmacodynamics (PD), genetic diversity explains only a limited proportion of IVDR. The role of gut microbiota, also known as the second genome, and its metabolites in modulating therapeutic outcomes in human diseases have been highlighted by recent studies. Consequently, the burgeoning field of pharmacomicrobiomics aims to explore the correlation between microbiota variation and IVDR or ADRs. This review presents an up-to-date overview of the intricate interactions between gut microbiota and classical therapeutic agents for human systemic diseases, including cancer, cardiovascular diseases (CVDs), endocrine diseases, and others. We summarise how microbiota, directly and indirectly, modify the absorption, distribution, metabolism, and excretion (ADME) of drugs. Conversely, drugs can also modulate the composition and function of gut microbiota, leading to changes in microbial metabolism and immune response. We also discuss the practical challenges, strategies, and opportunities in this field, emphasizing the critical need to develop an innovative approach to multi-omics, integrate various data types, including human and microbiota genomic data, as well as translate lab data into clinical practice. To sum up, pharmacomicrobiomics represents a promising avenue to address IVDR and improve patient outcomes, and further research in this field is imperative to unlock its full potential for precision medicine.
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Affiliation(s)
- Qing Zhao
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, PR China
| | - Yao Chen
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, PR China
| | - Weihua Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, PR China
| | - Honghao Zhou
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, PR China
| | - Wei Zhang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China.
- The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, PR China.
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, PR China.
- Central Laboratory of Hunan Cancer Hospital, Central South University, 283 Tongzipo Road, Changsha, 410013, PR China.
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5
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Chen M, Zhong W, Xu W. Alcohol and the mechanisms of liver disease. J Gastroenterol Hepatol 2023; 38:1233-1240. [PMID: 37423758 DOI: 10.1111/jgh.16282] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/13/2023] [Accepted: 06/14/2023] [Indexed: 07/11/2023]
Abstract
Alcoholic liver disease (ALD), which is a leading cause of morbidity and mortality worldwide, covers a large spectrum of liver injuries ranging from simple steatosis to steatohepatitis, advanced fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of ALD includes genetic and epigenetic alterations, oxidative stress, acetaldehyde-mediated toxicity and cytokine and chemokine-induced inflammation, metabolic reprogramming, immune damage, and dysbiosis of the gut microbiota. This review discusses the progress in the pathogenesis and molecular mechanism of ALD, which could provide evidence for further research on the potential therapeutic strategies targeting these pathways.
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Affiliation(s)
- Mo Chen
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wanglei Zhong
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Weiqi Xu
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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6
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Sun C, Zhou X, Guo T, Meng J. The immune role of the intestinal microbiome in knee osteoarthritis: a review of the possible mechanisms and therapies. Front Immunol 2023; 14:1168818. [PMID: 37388748 PMCID: PMC10306395 DOI: 10.3389/fimmu.2023.1168818] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 06/02/2023] [Indexed: 07/01/2023] Open
Abstract
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage damage and synovial inflammation and carries an enormous public health and economic burden. It is crucial to uncover the potential mechanisms of OA pathogenesis to develop new targets for OA treatment. In recent years, the pathogenic role of the gut microbiota in OA has been well recognized. Gut microbiota dysbiosis can break host-gut microbe equilibrium, trigger host immune responses and activate the "gut-joint axis", which aggravates OA. However, although the role of the gut microbiota in OA is well known, the mechanisms modulating the interactions between the gut microbiota and host immunity remain unclear. This review summarizes research on the gut microbiota and the involved immune cells in OA and interprets the potential mechanisms for the interactions between the gut microbiota and host immune responses from four aspects: gut barrier, innate immunity, adaptive immunity and gut microbiota modulation. Future research should focus on the specific pathogen or the specific changes in the gut microbiota composition to identify the related signaling pathways involved in the pathogenesis of OA. In addition, future studies should include more novel interventions on immune cell modifications and gene regulation of specific gut microbiota related to OA to validate the application of gut microbiota modulation in the onset of OA.
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Affiliation(s)
- Chang Sun
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Xing Zhou
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Ting Guo
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jia Meng
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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7
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Boicean A, Birlutiu V, Ichim C, Anderco P, Birsan S. Fecal Microbiota Transplantation in Inflammatory Bowel Disease. Biomedicines 2023; 11:biomedicines11041016. [PMID: 37189634 DOI: 10.3390/biomedicines11041016] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/21/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn’s disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host’s immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.
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8
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Aydin OC, Aydın S, Barun S. Role of natural products and intestinal flora on type 2 diabetes mellitus treatment. World J Clin Cases 2023; 11:65-72. [PMID: 36687192 PMCID: PMC9846977 DOI: 10.12998/wjcc.v11.i1.65] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/12/2022] [Accepted: 12/15/2022] [Indexed: 01/04/2023] Open
Abstract
Diabetes mellitus (DM) is a complicated, globally expanding disease that is influenced by hereditary and environmental variables. Changes in modern society's food choices, physical inactivity, and obesity are significant factors in the development of type 2 DM (T2DM). The association between changes in intestinal flora and numerous disorders, including obesity, diabetes, and cardiovascular diseases, has been studied in recent years. The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients' intestinal flora, as well as their therapeutic choices. Also included is a summary of the anti-diabetic benefits of natural compounds demonstrated by studies. The short-chain fatty acids theory, the bile acid theory, and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM. Due to an intestinal flora imbalance, abnormalities in short-chain fatty acids and secondary bile acids have been found in diabetic patients. Additionally, metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation. The agenda for diabetes treatment includes the use of short-chain fatty acids, probiotics, prebiotics in the diet, fecal bacteria transplantation, and antibiotics. Animal studies have proven the antidiabetic benefits of numerous bioactive substances, including Flavonoids, Alkaloids, Saponin, and Allicin. However, further research is required to contribute to the treatment of diabetes.
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Affiliation(s)
- Ozlem Celik Aydin
- Department of Medical Pharmacology, Erzincan Mengücek Gazi Training and Research Hospital, Erzincan 24100, Turkey
| | - Sonay Aydın
- Department of Radiology, Erzincan Binali Yıldırım University, Mengücek Gazi Training and Research Hospital, Erzincan 24100, Turkey
| | - Sureyya Barun
- Department of Medical Pharmacology, Gazi University Faculty of Medicine, Ankara 06500, Turkey
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9
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Ma Y, Ke D, Li D, Zhang Q. Donors' experiences and attitudes of fecal microbiota transplantation: An empirical bioethics study from China. IMETA 2022; 1:e62. [PMID: 38867907 PMCID: PMC10989884 DOI: 10.1002/imt2.62] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 09/12/2022] [Accepted: 10/22/2022] [Indexed: 06/14/2024]
Abstract
Donor participation is a critical part of ensuring the development of human microbiome research and the clinical application of fecal microbiota transplantation (FMT). Most FMT donors are still not sufficiently aware of the risks associated with the act of donating gut microbiota, especially the risk of data privacy disclosure. Enhanced awareness of the moral responsibility of the researchers and ethical oversight by ethics committees are needed.
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Affiliation(s)
- Yonghui Ma
- Medical Humanities and Bioethics Center, School of MedicineXiamen UniversityXiamenChina
| | - Dawei Ke
- Medical Humanities and Bioethics Center, School of MedicineXiamen UniversityXiamenChina
| | - Danyi Li
- R Institute Co. Ltd.BeijingChina
| | - Quan Zhang
- National Institute for Data Science in Health and MedicineXiamen UniversityXiamenChina
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10
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Peroumal D, Sahu SR, Kumari P, Utkalaja BG, Acharya N. Commensal Fungus Candida albicans Maintains a Long-Term Mutualistic Relationship with the Host To Modulate Gut Microbiota and Metabolism. Microbiol Spectr 2022; 10:e0246222. [PMID: 36135388 PMCID: PMC9603587 DOI: 10.1128/spectrum.02462-22] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 09/12/2022] [Indexed: 01/04/2023] Open
Abstract
Candida albicans survives as a commensal fungus in the gastrointestinal tract, and that its excessive growth causes infections in immunosuppressed individuals is widely accepted. However, any mutualistic relationship that may exist between C. albicans and the host remains undetermined. Here, we showed that a long-term feeding of C. albicans does not cause any noticeable infections in the mouse model. Our 16S and 18S ribosomal DNA (rDNA) sequence analyses suggested that C. albicans colonizes in the gut and modulates microbiome dynamics, which in turn mitigates high-fat-diet-induced uncontrolled body weight gain and metabolic hormonal imbalances. Interestingly, adding C. albicans to a nonobesogenic diet stimulated the appetite-regulated hormones and helped the mice maintain a healthy body weight. In concert, our results suggest a mutualism between C. albicans and the host, contrary to the notion that C. albicans is always an adversary and indicating it can instead be a bona fide admirable companion of the host. Finally, we discuss its potential translational implication as a probiotic, especially in obese people or people dependent on high-fat calorie intakes to manage obesity associated complications. IMPORTANCE Candida albicans is mostly considered an opportunistic pathogen that causes fetal systemic infections. However, this study demonstrates that in its commensal state, it maintains a long-term mutualistic relationship with the host and regulates microbial dynamics in the gut and host physiology. Thus, we concluded that C. albicans is not always an adversary but rather can be a bona fide admirable companion of the host. More importantly, as several genomic knockout strains of C. albicans were shown to be avirulent, such candidate strains may be explored further as preferable probiotic isolates to control obesity.
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Affiliation(s)
- Doureradjou Peroumal
- Laboratory of Genomic Instability and Diseases, Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India
| | - Satya Ranjan Sahu
- Laboratory of Genomic Instability and Diseases, Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India
- Regional Centre for Biotechnology, Faridabad, India
| | - Premlata Kumari
- Laboratory of Genomic Instability and Diseases, Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India
- Regional Centre for Biotechnology, Faridabad, India
| | - Bhabasha Gyanadeep Utkalaja
- Laboratory of Genomic Instability and Diseases, Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India
- Regional Centre for Biotechnology, Faridabad, India
| | - Narottam Acharya
- Laboratory of Genomic Instability and Diseases, Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India
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11
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Ke S, Weiss ST, Liu YY. Rejuvenating the human gut microbiome. Trends Mol Med 2022; 28:619-630. [PMID: 35781423 PMCID: PMC9339459 DOI: 10.1016/j.molmed.2022.05.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/23/2022] [Accepted: 05/03/2022] [Indexed: 12/13/2022]
Abstract
Industrial advances have caused significant loss of diversity in our gut microbiome, potentially increasing our susceptibility to many diseases. Recently, rewilding the human gut microbiome - that is, bringing it back to an ancestral or preindustrial state (e.g., by transplanting stool material from donors in nonindustrial societies) - has been hotly debated from medical, ethical, and evolutionary perspectives. Here we propose an alternative solution: rejuvenating the human gut microbiome by stool banking and autologous fecal microbiota transplantation, that is, collecting the hosts' stool samples at a younger age when they are at optimal health, and cryopreserving the samples in a stool bank for the hosts' own future use. In this article we discuss the motivation, applications, feasibility, and challenges of this solution.
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Affiliation(s)
- Shanlin Ke
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Scott T Weiss
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Yang-Yu Liu
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
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12
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Riva A, Pozzati E, Grasso M, De Caro C, Russo E, Verrotti A, Striano P. Targeting the MGBA with -biotics in epilepsy: New insights from preclinical and clinical studies. Neurobiol Dis 2022; 170:105758. [PMID: 35588991 DOI: 10.1016/j.nbd.2022.105758] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 05/09/2022] [Accepted: 05/11/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Data accumulation reveals that the bidirectional communication between the gut microbiota and the brain, called the microbiota-gut-brain axis (MGBA), can be modulated by different compounds including prebiotics, probiotics, symbiotic (a fair combination of both), and diet, thus exerting a beneficial impact on brain activity and behaviors. This review aims to give an overview of the possible beneficial effects of the supplementation of -biotics in epilepsy treatment. METHODS A search on PubMed and ClinicalTrials.gov databases using the terms "probiotics", OR "prebiotics", AND "gut microbiota", AND "epilepsy" was performed. The search covered the period of the last eleven years (2010-2021). CONCLUSIONS Nowadays, studies analyzing the clinical impact of gut microbiota-modulating intervention strategies on epilepsy are limited and heterogenous due either to the different experimental populations studied (i.e., genetic vs lesional mouse models) or the various primary outcomes measure evaluated. However, positive effects have invariably been noticed; particularly, there have been improvements in behavioral comorbidities and associated gastrointestinal (GI) symptoms. More studies will be needed in the next few years to strictly evaluate the feasibility to introduce these new therapeutic strategies in the clinical treatment of highly refractory epilepsies.
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Affiliation(s)
- Antonella Riva
- Paediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova, Genova, Italy
| | - Elisa Pozzati
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova, Genova, Italy
| | - Mattia Grasso
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova, Genova, Italy
| | - Carmen De Caro
- Science of Health Department, School of Medicine, University of Catanzaro, Catanzaro, Italy
| | - Emilio Russo
- Science of Health Department, School of Medicine, University of Catanzaro, Catanzaro, Italy
| | - Alberto Verrotti
- Department of Paediatrics, University of Perugia, Perugia, Italy
| | - Pasquale Striano
- Paediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova, Genova, Italy.
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13
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Garbuzenko DV. Principles of diagnosis and treatment of alcohol-induced liver fibrosis. MEDITSINSKIY SOVET = MEDICAL COUNCIL 2022. [DOI: 10.21518/2079-701x-2022-16-7-104-114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Alcohol-related liver diseases are one of the leading causes of death worldwide, primarily due to complications of liver cirrhosis (LC). Early detection of alcohol-induced liver fibrosis (LF) is a difficult task, since often alcoholic liver disease (ALD) is clinically manifested only at late stages. Given that not all alcoholic suffer from ALD, the widespread use of liver biopsy to verify the diagnosis is not advisable. Despite the variety of proposed non-invasive methods for assessing the severity of LF in patients with ALD, none of them has sufficient validation and therefore cannot be recommended for widespread use in clinical practice. The most well-studied transient elastography, due to its suboptimal specificity, can be effectively used only to exclude clinically significant LF or LC. The only proven approach to treat ALD is persistent and total alcohol abstinence. While the therapeutic options for patients with severe forms of acute hepatitis remain unchanged since the 70s of the last century and are based mainly on the use of corticosteroids, currently, there are no approaches to antifibrotic therapy of ALD approved by the guidelines. At the same time, modern achievements in understanding the pathophysiological mechanisms of this disease have served as an impetus for the development of ways to solve the problem. In particular, providing intestinal eubiosis may be an important goal for the prevention and treatment of alcohol-induced LF. Randomized controlled multicenter trials involving a large number of patients are needed to confirm this and other hypotheses related to antifibrotic therapy of ALD and to accept them as a standard of medical care.
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Ramires LC, Santos GS, Ramires RP, da Fonseca LF, Jeyaraman M, Muthu S, Lana AV, Azzini G, Smith CS, Lana JF. The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut? Int J Mol Sci 2022; 23:1494. [PMID: 35163417 PMCID: PMC8835947 DOI: 10.3390/ijms23031494] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/11/2022] [Accepted: 01/25/2022] [Indexed: 02/05/2023] Open
Abstract
Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.
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Affiliation(s)
- Luciano C. Ramires
- Department of Orthopaedics and Sports Medicine, Mãe de Deus Hospital, Porto Alegre 90110-270, RS, Brazil;
| | - Gabriel Silva Santos
- Department of Orthopaedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, SP, Brazil; (G.A.); (J.F.L.)
| | - Rafaela Pereira Ramires
- Department of Biology, Cellular, Molecular and Biomedical Science, Boise State University, 1910 W University Drive, Boise, ID 83725, USA;
| | - Lucas Furtado da Fonseca
- Department of Orthopaedics, The Federal University of São Paulo, São Paulo 04024-002, SP, Brazil
| | - Madhan Jeyaraman
- Department of Orthopaedics, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India;
| | - Sathish Muthu
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624304, Tamil Nadu, India;
| | - Anna Vitória Lana
- Department of Medicine, Max Planck University Center, Indaiatuba 13343-060, SP, Brazil;
| | - Gabriel Azzini
- Department of Orthopaedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, SP, Brazil; (G.A.); (J.F.L.)
| | - Curtis Scott Smith
- Department of Medicine, University of Washington School of Medicine, Seattle, WA 83703, USA;
| | - José Fábio Lana
- Department of Orthopaedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, SP, Brazil; (G.A.); (J.F.L.)
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Zare M, Vehreschild MJGT, Wagenlehner F. Management of uncomplicated recurrent urinary tract infections. BJU Int 2021; 129:668-678. [PMID: 34741796 DOI: 10.1111/bju.15630] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To discuss optimal management of recurrent urinary tract infections (UTIs) in women. About every second woman experiences at least one UTI in her lifetime, of those 30% experience another UTI, and 3% further recurrences. Especially young healthy women without underlying anatomical deficiencies suffer from recurrent UTIs (rUTI), which are associated with significant morbidity and reduction in quality of life. METHODS This is a narrative review, investigating publications dealing with recurrent UTI in women. Risk factors and options for management are discussed. RESULTS The increased susceptibility of women to rUTI is based on the female anatomy in addition to behavioural, genetic, and urological factors. However, why some women are more likely than others to develop and maintain rUTI remains to be clarified. Invasive characteristics of certain uropathogenic Escherichia coli that are able to form extra- and intracellular biofilms and may therefore cause delayed release of bacteria into the bladder, may play a role in this setting. Treatment recommendations for an acute episode of rUTI do not differ from those for isolated episodes. Given the nature of rUTI, different prophylactic approaches also play an important role. Women with rUTI should first be counselled to use non-antibiotic strategies including behavioural changes, anti-adhesive treatments, antiseptics, and immunomodulation, before antibiotic prophylaxis is considered. In addition to the traditional treatment and prophylactic therapies, new experimental strategies are emerging and show promising effects, such as faecal microbiota transfer (FMT), a treatment option that transfers microorganisms and metabolites of a healthy donor's faecal matter to patients using oral capsules, enemas, or endoscopy. Initial findings suggest that FMT might be a promising treatment approach to interrupt the cycle of rUTI. Furthermore, bacteriophages, infecting and replicating in bacteria, have been clinically trialled for UTIs. CONCLUSION Due to the limitation of available data, novel treatment options require further clinical research to objectify the potential in treating bacterial infections, particularly UTIs.
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Affiliation(s)
- Mary Zare
- Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Maria J G T Vehreschild
- Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Florian Wagenlehner
- Department of Urology, Pediatric Urology and Andrology, Justus Liebig University of Giessen, Giessen, Germany
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Liu L, Wang Y, Zhang J, Wang C, Li Y, Dai W, Piao C, Liu J, Yu H, Li X, Wang Y, Liu J. Probiotics in treating with alcoholic liver disease and nonalcoholic fatty liver disease. FOOD REVIEWS INTERNATIONAL 2021. [DOI: 10.1080/87559129.2021.1967380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Lingchong Liu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- College of Life Science, Changchun Sci-Tech University, Changchun, China
| | - Yu Wang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
| | - Jing Zhang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
| | - Chao Wang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
| | - Youbao Li
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Weichang Dai
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Chunhong Piao
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Junmei Liu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Hansong Yu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Xia Li
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Yuhua Wang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Jingsheng Liu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
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Dixit K, Chaudhari D, Dhotre D, Shouche Y, Saroj S. Restoration of dysbiotic human gut microbiome for homeostasis. Life Sci 2021; 278:119622. [PMID: 34015282 DOI: 10.1016/j.lfs.2021.119622] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/08/2021] [Accepted: 05/11/2021] [Indexed: 02/07/2023]
Abstract
The human microbiome is a complex and dynamic ecosystem, and the imbalance of its microbial community structure from the normal state is termed dysbiosis. The dysbiotic gut microbiome has been proved to be related to several pathological conditions like Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Colorectal Cancer (CRC), etc., and several other extra-intestinal conditions like Type 1 & 2 diabetes, obesity, etc. The complex gut microbial ecosystem starts to build before the birth of an individual. It is known to get affected by several factors such as birth mode, individual lifestyle, dietary practices, medications, and antibiotics. A dysbiotic microbiome can potentially hamper host homeostasis due to its role in immune modulation, metabolism, nutrient synthesis, etc. Restoration of the dysbiotic gut microbiome has emerged as a promising aid and a better therapeutic approach. Several approaches have been investigated to achieve this goal, including prebiotics and probiotics, Fecal Microbiota Transplantation (FMT), extracellular vesicles, immune modulation, microbial metabolites, dietary interventions, and phages. This review discusses the various factors that influence the human microbiome with respect to their cause-effect relationship and the effect of gut microbiome compositional changes on the brain through the gut-brain axis. We also discuss the practices used globally for gut microbiome restoration purposes, along with their effectiveness.
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Affiliation(s)
- Kunal Dixit
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Pune, India
| | - Diptaraj Chaudhari
- National Center for Microbial Resource (NCMR), National Center for Cell Science (NCCS), Pune, India
| | - Dhiraj Dhotre
- Innovative Technology Group, Reliance Life Sciences Pvt Ltd., Navi-Mumbai, India
| | - Yogesh Shouche
- National Center for Microbial Resource (NCMR), National Center for Cell Science (NCCS), Pune, India
| | - Sunil Saroj
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Pune, India.
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De Musis C, Granata L, Dallio M, Miranda A, Gravina AG, Romano M. Inflammatory Bowel Diseases: The Role of Gut Microbiota. Curr Pharm Des 2021; 26:2951-2961. [PMID: 32310042 DOI: 10.2174/1381612826666200420144128] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022]
Abstract
Inflammatory bowel diseases (IBD) are chronic multifactorial diseases characterized by partially unclear pathogenic mechanisms including changes in intestinal microbiota. Despite the microbiota, alteration is well established in IBD patients, as reported by 16RNA sequencing analysis, an important goal is to define if it is just a consequence of the disease progression or a trigger factor of the disease itself. To date, gut microbiota composition and gut microbiota-related metabolites seem to affect the host healthy state both by modulating metabolic pathways or acting on the expression of different genes through epigenetic effects. Because of this, it has been suggested that intestinal microbiota might represent a promising therapeutic target for IBD patients. The aim of this review is to summarize both the most recent acquisitions in the field of gut microbiota and its involvement in intestinal inflammation together with the available strategies for the modulation of microbiota, such as prebiotics and/or probiotics administration or fecal microbiota transplantation.
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Affiliation(s)
- Cristiana De Musis
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ''Luigi Vanvitelli'' and University Hospital, Naples, Italy
| | - Lucia Granata
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ''Luigi Vanvitelli'' and University Hospital, Naples, Italy
| | - Marcello Dallio
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ''Luigi Vanvitelli'' and University Hospital, Naples, Italy
| | - Agnese Miranda
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ''Luigi Vanvitelli'' and University Hospital, Naples, Italy
| | - Antonietta G Gravina
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ''Luigi Vanvitelli'' and University Hospital, Naples, Italy
| | - Marco Romano
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ''Luigi Vanvitelli'' and University Hospital, Naples, Italy
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Zhang W, Zou G, Li B, Du X, Sun Z, Sun Y, Jiang X. Fecal Microbiota Transplantation (FMT) Alleviates Experimental Colitis in Mice by Gut Microbiota Regulation. J Microbiol Biotechnol 2020; 30:1132-1141. [PMID: 32423189 PMCID: PMC9728197 DOI: 10.4014/jmb.2002.02044] [Citation(s) in RCA: 113] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 05/10/2020] [Indexed: 12/15/2022]
Abstract
Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.
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Affiliation(s)
- Wanying Zhang
- Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, P.R. China,Heilongjiang Longwei Precision Medical Laboratory Center, Longchuan Road, Songbei District, Harbin 150028, P.R. China
| | - Guiling Zou
- Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, P.R. China,Heilongjiang Longwei Precision Medical Laboratory Center, Longchuan Road, Songbei District, Harbin 150028, P.R. China
| | - Bin Li
- Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, P.R. China,Heilongjiang Longwei Precision Medical Laboratory Center, Longchuan Road, Songbei District, Harbin 150028, P.R. China
| | - Xuefei Du
- Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, P.R. China,Heilongjiang Longwei Precision Medical Laboratory Center, Longchuan Road, Songbei District, Harbin 150028, P.R. China
| | - Zhe Sun
- Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, P.R. China,Heilongjiang Longwei Precision Medical Laboratory Center, Longchuan Road, Songbei District, Harbin 150028, P.R. China
| | - Yu Sun
- Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, P.R. China,Heilongjiang Longwei Precision Medical Laboratory Center, Longchuan Road, Songbei District, Harbin 150028, P.R. China
| | - Xiaofeng Jiang
- Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, P.R. China,Heilongjiang Longwei Precision Medical Laboratory Center, Longchuan Road, Songbei District, Harbin 150028, P.R. China,Corresponding author Phone: +86-0451-85716079 Fax: +86-0451-85716079 E-mail:
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Stallmach A, Steube A, Grunert P, Hartmann M, Biehl LM, Vehreschild MJGT. Fecal Microbiota Transfer. DEUTSCHES ARZTEBLATT INTERNATIONAL 2020; 117:31-38. [PMID: 32031511 DOI: 10.3238/arztebl.2020.0031] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 08/19/2019] [Accepted: 11/05/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Fecal microbiota transfer (FMT) is increasingly being used in Ger- many, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary. METHODS This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad. RESULTS Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI. CONCLUSION Encapsulation of the fecal microbiome (FM) and storage at -20°C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active e FM. It is not yet clear when the ultimate goal of recombinant production can be achieved.
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Affiliation(s)
- Andreas Stallmach
- Department of Internal Medicine IV (Gastroenterology, Hepatology, Infectious Diseases), Jena University Hospital, Jena, Germany; University Pharmacy, Jena University Hospital, Jena, Germany; University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen, Bonn, Cologne, Duesseldorf, Germany; German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Germany; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
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Abstract
Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders including steatosis, steatohepatitis, fibrosis, and cirrhosis. Despite intensive research in the last two decades, there is currently no Food and Drug Administration-approved therapy for treating ALD. Several studies have demonstrated the importance of the gut-liver axis and gut microbiome on the pathogenesis of ALD. Alcohol may induce intestinal dysbiosis and increased intestinal permeability, which in turn result in increased levels of pathogen-associated molecular patterns such as lipopolysaccharide (LPS) and translocation of microbial products from the gut to the liver (bacterial translocation). LPS is an inflammatory signal that activates toll-like receptor 4 on Kupffer cells, contributing to the inflammation observed in ALD. Recently, probiotics have been shown to be effective in reducing or preventing the progression of ALD. A potential mechanism is that the probiotics transforms the composition of intestinal microbiota, which leads to reductions in alcohol-induced dysbiosis, intestinal permeability, bacterial translocation, endotoxemia, and consequently, the development of ALD. While transformation of intestinal microbiota by probiotics appears to be a promising therapeutic strategy for the treatment of intestinal barrier dysfunction, there is a scarcity of research that studies probiotics in the context of ALD. In this review, we discuss the potential therapeutic applications of probiotics in the treatment of ALD.
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Jin CY, Hu Y, Jin B. Faecal microbiota transplantation: Application in treatment of some digestive diseases and safety concerns. Shijie Huaren Xiaohua Zazhi 2020; 28:135-143. [DOI: 10.11569/wcjd.v28.i4.135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Intestinal microbiota is an essential part of the body, and it closely relates to normal functioning of the host as well as the onset of a variety of diseases. Faecal microbiota transplantation (FMT) is the major method to modify the intestinal dysbiosis. Currently, it has been approved for treatment of refractory/recurrent Clostridium difficile infection by the US Food and Drug Administration. Clinical trials also suggested that FMT may have effects on a variety of systemic diseases. In this paper, we briefly reviewed the current status of FMT application in most studied digestive diseases such as inflammatory bowel diseases, hepatic encephalopathy, irritable bowel syndrome, and cancer. The adverse effects and complications disclosed in these studies are analyzed in the context of current administrative rules, and safety concerns are discussed.
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Affiliation(s)
- Cheng-Yue Jin
- Beijing Zhongyan Chinese Medicine Hospital, Beijing 102401, China
| | - Ying Hu
- Beijing Zhongyan Chinese Medicine Hospital, Beijing 102401, China
| | - Bo Jin
- The 8th Medical Center, Chinese PLA General Hospital, Beijing 100091, China
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Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease. Int J Hepatol 2020; 2020:1874570. [PMID: 32047670 PMCID: PMC7007953 DOI: 10.1155/2020/1874570] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 12/22/2019] [Accepted: 01/17/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant Clostridioides difficile infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive. AIMS We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center. METHODS A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or recurrent CDI was identified. Patients were monitored for a year after FMT. Descriptive analysis was conducted to compare the effect of FMT in patients with and without CLD. RESULTS A total of 201 patients with CDI received FMT, 14 of which had a history of CLD. Nine of these patients exhibited cirrhosis of the liver with a mean Child-Turcotte-Pugh score of 8. CDI development in these patients was associated with recent exposure to antibiotics and was observed to be significantly different between both groups (17% of CLD patients vs. 58% in the general cohort, p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%). CONCLUSION FMT is a safe and effective therapy against CDI for patients with CLD and cirrhosis.
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Feehan A, Garcia-Diaz J. Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms. Microorganisms 2020; 8:microorganisms8020166. [PMID: 31991615 PMCID: PMC7074682 DOI: 10.3390/microorganisms8020166] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 01/17/2020] [Accepted: 01/17/2020] [Indexed: 02/07/2023] Open
Abstract
Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.
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Affiliation(s)
- Amy Feehan
- Infectious Disease Department, Ochsner Clinic Foundation, New Orleans, LA 70121, USA;
| | - Julia Garcia-Diaz
- Infectious Disease Department, Ochsner Clinic Foundation, New Orleans, LA 70121, USA;
- The University of Queensland Faculty of Medicine, Ochsner Clinical School, New Orleans, LA 70121, USA
- Correspondence: ; Tel.: +1-504-842-4005
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Abstract
Microbiome dysbiosis is strongly associated with alcoholic liver disease (ALD). Recent studies on comprehensive analyses of microbiome compositional and functional changes have begun to uncover the mechanistic relation between microbiome and the pathogenesis of ALD. Importantly, targeting the microbiome has become a potential strategy for the prevention and treatment of ALD. In this review, we summarize the clinical evidence of microbiome dysbiosis in ALD patients, and experimental advances in microbiome and metabolomic functional changes in animals with different species and genetic backgrounds in ALD. We also summarize the studies in humanized intestinal microbiome and fecal microbiota transplantation in mice. We introduce new developments in the studies on the role of the circulating bacterial microbiome, oral bacterial microbiome and fungal microbiome in the development of ALD. We highlight the potential mechanisms by which microbiome dysbiosis contributes to ALD, including short chain fatty acid changes, bile acid metabolism, intestinal barrier function, release of bacterial and fungal products, and inflammation. In addition, we summarize the recent developments targeting the microbiome in prevention and treatment of ALD, including dietary nutrient interference, herbal medicine, antibiotics, anti-fungal agents, probiotics, engineered bacterial therapy, fecal transplantation and oral hygiene. Although recent preclinical studies have advanced our understanding of the microbiome and ALD, clinical studies, especially prospective studies with large samples, are needed to better understand the cause-effect of microbiome dysbiosis in ALD. Identifying new precision-based strategies targeting the microbiome are expected to be developed as more effective therapies in ALD.
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Abstract
Many studies have indicated that intestinal barrier dysfunction is the key mechanism of alcoholic liver disease (ALD). In this paper, we systematically review the causes of intestinal barrier dysfunction and the pathogenesis of ALD and discuss the treatment of intestinal barrier dysfunction.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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Pezo RC, Wong M, Martin A. Impact of the gut microbiota on immune checkpoint inhibitor-associated toxicities. Therap Adv Gastroenterol 2019; 12:1756284819870911. [PMID: 31555343 PMCID: PMC6747860 DOI: 10.1177/1756284819870911] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 07/17/2019] [Indexed: 02/04/2023] Open
Abstract
Immune checkpoint inhibitors (ICIs) have transformed the treatment of patients with advanced cancers. However, the majority of patients do not respond or develop early progressive disease. A substantial number also develop immune-mediated toxicities that may lead to early treatment discontinuation. Gastrointestinal toxicities in the form of diarrhea and colitis are common and may resemble that observed in patients with inflammatory bowel disease (IBD). Alterations in the gut microbiota are thought to play an important role in mediating the intestinal inflammation that is associated with immune-mediated colitis. In this review, the authors' objective is to provide an overview of the gastrointestinal and hepatic toxicities that can be seen with ICIs and discuss the interactions between gut microbiota and the immune response. The authors also highlight the potential role for fecal microbial transfer (FMT) as an approach to improve therapeutic efficacy and decrease toxicity.
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Affiliation(s)
| | - Matthew Wong
- Department of Immunology, University of Toronto, Toronto, ON, Canada
| | - Alberto Martin
- Department of Immunology, University of Toronto, Toronto, ON, Canada
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Alcohol or Gut Microbiota: Who Is the Guilty? Int J Mol Sci 2019; 20:ijms20184568. [PMID: 31540133 PMCID: PMC6770333 DOI: 10.3390/ijms20184568] [Citation(s) in RCA: 127] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 09/11/2019] [Accepted: 09/12/2019] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.
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Wu X, Dai M, Buch H, Bai J, Long W, Long C, Tang X, Tu H, Zhang R, Zhu C, Yang S, Cui B, Ji G, Zhang F. The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study. Therap Adv Gastroenterol 2019; 12:1756284819869144. [PMID: 31516555 PMCID: PMC6724572 DOI: 10.1177/1756284819869144] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 06/28/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Physicians and medical students in the world do not have high awareness of fecal microbiota transplantation (FMT). This study aimed to explore the recognition and attitude of postgraduate medical students towards FMT and to create awareness for it. METHODS A self-administered questionnaire was distributed to first-year Chinese postgraduate medical students across six medical universities. Basic descriptive statistical analyses were performed. RESULTS A total of 1828 eligible questionnaires were included into analysis. 47.76% of students did not know FMT prior to this survey. Respondents with a high-level recognition of FMT were more willing to donate feces or receive FMT therapy than those with a low-level recognition (80.26% vs. 69.62%, p = 0.000 and 56.80% vs. 41.45%, p = 0.000). The respondents from a leading institution of FMT in China showed better awareness compared with others, and 42.26% of them knew about FMT from medical lectures. The main reasons for respondents not supporting FMT were: limited reported clinical evidence (67.94%), raw technology (42.56%), and lack of analysis of patient willingness or cost-effectiveness (36.71%). However, the life-saving value (84.41%), the automatic purification system (38.68%), low expenses (36.00%), and convenient delivering ways (35.67%) were the major considerations for supporting FMT. CONCLUSIONS This study revealed the low recognition level of postgraduate medical students about FMT. Therefore, medical education should not neglect the knowledge of FMT. Studies of FMT and standardized FMT should be carried out to promote its development.
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Affiliation(s)
| | | | - Heena Buch
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianling Bai
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Wenwu Long
- Jiangxi Medical College of Nanchang University, Nanchang, China
| | - Chuyan Long
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xianyan Tang
- Department of Epidemiology and Biostatistics, School of Public Health, Guangxi Medical University, Guangxi Zhuang Autonomous Region, China
| | - Hua Tu
- Department of Gastroenterology, Hubei Provincial Hospital Traditional Chinese Medicine, Wuhan, China
| | - Renjie Zhang
- Hubei University of Chinese Medicine, Wuhan, China
| | - Cairong Zhu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Shaoqi Yang
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guozhong Ji
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Borody TJ, Clancy A. Fecal microbiota transplantation for ulcerative colitis-where to from here? Transl Gastroenterol Hepatol 2019; 4:48. [PMID: 31304425 DOI: 10.21037/tgh.2019.06.04] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 06/13/2019] [Indexed: 12/15/2022] Open
Affiliation(s)
- Thomas J Borody
- Centre for Digestive Diseases, Five Dock, Sydney, NSW, Australia
| | - Annabel Clancy
- Centre for Digestive Diseases, Five Dock, Sydney, NSW, Australia
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Turse EP, Dailey FE, Ghouri YA, Tahan V. Fecal microbiota transplantation donation: the gift that keeps on giving. Curr Opin Pharmacol 2019; 49:24-28. [PMID: 31085417 DOI: 10.1016/j.coph.2019.04.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Accepted: 04/08/2019] [Indexed: 12/13/2022]
Abstract
Fecal microbiota transplantation (FMT) is being studied and utilized for various medical conditions including Clostridium difficile colitis, inflammatory bowel diseases (IBD), obesity, myasthenia gravis, and so on. Yet, FMT donation, whether from an individual or a stool bank, can be challenging given the numerous requirements and donor costs. Furthermore, data outcomes on recipients of FMT regarding donor's health co-morbidities, age, and weight are limited but emerging. The purpose of this review is to evaluate cost, safety, and accessibility in FMT donation.
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Affiliation(s)
- Erica P Turse
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, St. Joseph's Hospital and Medical Center/Creighton University, Phoenix, AZ, USA
| | - Francis E Dailey
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Missouri-Columbia, Missouri, USA
| | - Yezaz A Ghouri
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Missouri-Columbia, Missouri, USA
| | - Veysel Tahan
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Missouri-Columbia, Missouri, USA.
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Help, hope and hype: ethical considerations of human microbiome research and applications. Protein Cell 2019; 9:404-415. [PMID: 29675808 PMCID: PMC5960465 DOI: 10.1007/s13238-018-0537-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Sarin SK, Pande A, Schnabl B. Microbiome as a therapeutic target in alcohol-related liver disease. J Hepatol 2019; 70:260-272. [PMID: 30658727 DOI: 10.1016/j.jhep.2018.10.019] [Citation(s) in RCA: 173] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 10/23/2018] [Indexed: 02/08/2023]
Abstract
Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids.
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Affiliation(s)
- Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - Apurva Pande
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
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Tabbaa OM, Aboelsoud MM, Mattar MC. Long-Term Safety and Efficacy of Fecal Microbiota Transplantation in the Treatment of Clostridium difficile Infection in Patients With and Without Inflammatory Bowel Disease: A Tertiary Care Center's Experience. Gastroenterology Res 2018; 11:397-403. [PMID: 30627262 PMCID: PMC6306107 DOI: 10.14740/gr1091] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Accepted: 10/08/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Clostridium difficile infection (CDI) carries a large burden on the national public health with its high morbidity and mortality rates. Patients with inflammatory bowel disease (IBD) are generally at higher risk of infection, recurrence and complications. Therefore, the need for more reliable and safe therapy is necessary. Our study aims to evaluate long-term fecal microbiota transplant (FMT) outcomes in the general population compared to patients with IBD. METHODS A single center long-term follow-up study was conducted to evaluate the outcomes of FMT in patients with and without IBD. Prior to FMT data including demographics, prior treatment of CDI and severity of symptoms were gathered via chart review. Post FMT, all patients were surveyed after 2 days, 30 days and > 1 year to assess clinical and laboratory response. Our study outcomes included primary cure rate (negative CDI testing > 1 year after single FMT), and secondary cure rate (negative CDI testing > 1 year after repeat FMT or after an additional course of antibiotic with or without repeat FMT). RESULTS Seventy-eight patients with recurrent or refractory CDI and subsequent FMT treatment were included. Mean age was 57 years, and 69% were females and twenty-one (27%) had IBD. Primary cure rate was achieved in 77% of the cases while secondary cure rate reached 100% at the end of the study. IBD patients were younger with an average age of 47 years, and had more complains of abdominal pain (71%), and required escalation of therapy in 50% of patients. CONCLUSIONS FMT was effective in the eradication of CDI in patients with and without IBD, but with no significant symptoms improvement in patients with IBD. Future randomized control studies are needed to examine the long-term progression of IBD and quality of life in patients treated with FMT compared to standard therapy of antibiotics for recurrent CDI.
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Affiliation(s)
- Obada M Tabbaa
- Department of Medicine, Medstar Washington Hospital Center, Washington, DC 20010, USA
| | - Mohammed M Aboelsoud
- Division of Gastroenterology and Hepatology, Medstar Georgetown University Hospital, Washington, DC 20007, USA
| | - Mark C Mattar
- Division of Gastroenterology and Hepatology, Medstar Georgetown University Hospital, Washington, DC 20007, USA
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Wei YL, Chen YQ, Gong H, Li N, Wu KQ, Hu W, Wang B, Liu KJ, Wen LZ, Xiao X, Chen DF. Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in Mice by Upregulating AhR. Front Microbiol 2018; 9:1921. [PMID: 30197631 PMCID: PMC6118168 DOI: 10.3389/fmicb.2018.01921] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 07/30/2018] [Indexed: 12/22/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is gaining attention as a clinical treatment of UC, the molecular mechanisms behind this effect have yet to be fully understood. A C57BL/6 mouse model was established to test whether FMT promotes the recovery of colon inflammation. Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as well as a decrease in body weight. FMT alleviated the severity of colon mucosa injury and improved histological alterations compared with that of the DSS group. In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore, FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in colon tissues. These results suggest that the significant anti-inflammatory effect of FMT may be attributed to its promotion of IL-10 and TGF-β production and AHR activation. Based on these results, FMT had a favorable therapeutic effect on DSS-induced colitis.
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Affiliation(s)
- Yan-Ling Wei
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Yu-Qin Chen
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Hao Gong
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Ning Li
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Kang-Qi Wu
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Wang Hu
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Bin Wang
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Kai-Jun Liu
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Liang-Zhi Wen
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Xiao Xiao
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
| | - Dong-Feng Chen
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital affiliated to the Army Medical University, Chongqing, China
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Bhutiani N, Schucht JE, Miller KR, McClave SA. Technical Aspects of Fecal Microbial Transplantation (FMT). Curr Gastroenterol Rep 2018; 20:30. [PMID: 29886561 DOI: 10.1007/s11894-018-0636-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW Fecal microbial transplantation (FMT) has become established as an effective therapeutic modality in the treatment of antibiotic-refractory recurrent Clostridium difficile colitis. A number of formulations and methods of delivery of FMT are currently available, each with distinct advantages. This review aims to review donor and patient selection for FMT as well as procedural aspects of FMT to help guide clinical practice. RECENT FINDINGS FMT can be obtained in fresh, frozen, lyophilized, and capsule-based formulations for delivery by oral ingestion, nasoenteric tube, colonoscopy, or enema (depending on the formulation used). Choosing the optimal method relies heavily on patient-related factors, including underlying pathology and severity of illness. As potential applications for FMT expand, careful donor screening and patient selection are critical to minimizing risk to patients and physicians. FMT represents an excellent therapeutic option for treatment of recurrent Clostridium difficile colitis and holds promise as a possible treatment modality in a variety of other conditions. The wide array of delivery methods allows for its application in various disease states in both the inpatient and outpatient setting.
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Affiliation(s)
- N Bhutiani
- Department of Surgery, Division of Trauma and Critical Care, University of Louisville, Louisville, KY, USA
| | - J E Schucht
- Department of Surgery, Division of Trauma and Critical Care, University of Louisville, Louisville, KY, USA
| | - K R Miller
- Department of Surgery, Division of Trauma and Critical Care, University of Louisville, Louisville, KY, USA
| | - Stephen A McClave
- Department of Medicine, Division of Gastroenterology, University of Louisville, 550 S. Jackson St., Ambulatory Care Building 3nd Floor, Louisville, KY, 40202, USA.
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Li S, Shao Y, Li K, HuangFu C, Wang W, Liu Z, Cai Z, Zhao B. Vascular Cognitive Impairment and the Gut Microbiota. J Alzheimers Dis 2018; 63:1209-1222. [PMID: 29689727 DOI: 10.3233/jad-171103] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Sinian Li
- Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Yiming Shao
- The Intensive Care Unit, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Kanglan Li
- Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Changmei HuangFu
- Department of Gerontology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Wenjie Wang
- Department of Neurosurgery, The Central Hospital of Longhua District, Shenzhen, China
| | - Zhou Liu
- Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Zhiyou Cai
- Department of Neurology, Chongqing General Hospital, Chongqing, China
| | - Bin Zhao
- Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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El-Salhy M, Mazzawi T. Fecal microbiota transplantation for managing irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2018; 12:439-445. [PMID: 29493330 DOI: 10.1080/17474124.2018.1447380] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder affecting 11.2% of the world adult population. The intestinal microbiome is thought to play a pivotal role in the pathophysiology of IBS. The composition of the fecal microbiome in IBS patients differs from that in healthy individuals, but the exact bacteria species involved in the development of IBS remain to be determined. There is also an imbalance between useful and harmful bacteria (dysbiosis) in the intestinal microbiome in patients with IBS. Consuming prebiotics, probiotics, or synbiotics has a limited effect on IBS symptoms. In contrast, fecal microbiome transplantation (FMT) in IBS patients reverses the dysbiosis to normobiosis and reduces the IBS symptoms in about 70% of patients, and is not associated with any serious adverse events. Area covered: The available data on the microbiome and FMT in IBS regarding the efficacy of FMT in managing IBS were found using a PubMed search of these topics. Expert commentary: FMT is a promising tool for managing irritable syndrome. It appears to be effective, easy, and inexpensive procedure. However, more controlled studies involving larger cohorts of IBS are needed before FMT can be used as a routine procedure in the clinic.
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Affiliation(s)
- Magdy El-Salhy
- a Section for Gastroenterology, Department of Medicine , Stord Hospital , Stord , Norway.,b Section for Gastroenterology, Department of Clinical Medicine , University of Bergen , Bergen , Norway
| | - Tarek Mazzawi
- b Section for Gastroenterology, Department of Clinical Medicine , University of Bergen , Bergen , Norway
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40
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Ma Y, Chen H, Lei R, Ren J. Biobanking for human microbiome research: promise, risks, and ethics. Asian Bioeth Rev 2017. [DOI: 10.1007/s41649-017-0033-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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Basson AR, Lam M, Cominelli F. Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches. Gastroenterol Clin North Am 2017; 46:689-729. [PMID: 29173517 PMCID: PMC5909826 DOI: 10.1016/j.gtc.2017.08.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential.
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Affiliation(s)
- Abigail R Basson
- Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Minh Lam
- Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Fabio Cominelli
- Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
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Zhou Z, Zhong W. Targeting the gut barrier for the treatment of alcoholic liver disease. LIVER RESEARCH 2017; 1:197-207. [PMID: 30034913 PMCID: PMC6051712 DOI: 10.1016/j.livres.2017.12.004] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Alcohol consumption remains one of the predominant causes of liver disease and liver-related death worldwide. Intriguingly, dysregulation of the gut barrier is a key factor promoting the pathogenesis of alcoholic liver disease (ALD). A functional gut barrier, which consists of a mucus layer, an intact epithelial monolayer and mucosal immune cells, supports nutrient absorption and prevents bacterial penetration. Compromised gut barrier function is associated with the progression of ALD. Indeed, alcohol consumption disrupts the gut barrier, increases gut permeability, and induces bacterial translocation both in ALD patients and in experimental models with ALD. Moreover, alcohol consumption also causes enteric dysbiosis with both numerical and proportional perturbations. Here, we review and discuss mechanisms of alcohol-induced gut barrier dysfunction to better understand the contribution of the gut-liver axis to the pathogenesis of ALD. Unfortunately, there is no effectual Food and Drug Administration-approved treatment for any stage of ALD. Therefore, we conclude with a discussion of potential strategies aimed at restoring the gut barrier in ALD. The principle behind antibiotics, prebiotics, probiotics and fecal microbiota transplants is to restore microbial symbiosis and subsequently gut barrier function. Nutrient-based treatments, such as dietary supplementation with zinc, niacin or fatty acids, have been shown to regulate tight junction expression, reduce intestinal inflammation, and prevent endotoxemia as well as liver injury caused by alcohol in experimental settings. Interestingly, saturated fatty acids may also directly control the gut microbiome. In summary, clinical and experimental studies highlight the significance and efficacy of the gut barrier in treating ALD.
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Affiliation(s)
- Zhanxiang Zhou
- Center for Translational Biomedical Research, School of Health and Human Sciences, University of North Carolina at Greensboro, Kannapolis, NC, USA
- Department of Nutrition, School of Health and Human Sciences, University of North Carolina at Greensboro, Greensboro, NC, USA
| | - Wei Zhong
- Center for Translational Biomedical Research, School of Health and Human Sciences, University of North Carolina at Greensboro, Kannapolis, NC, USA
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Khajah MA. The potential role of fecal microbiota transplantation in the treatment of inflammatory Bowel disease. Scand J Gastroenterol 2017; 52:1172-1184. [PMID: 28685630 DOI: 10.1080/00365521.2017.1347812] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of an unknown etiology. Its pathogenesis involves an interplay of infectious, genetic, environmental, and immunological factors. The current therapeutic options have various limitations in terms of cost, side effect profile, and the development of drug resistance and dependence. Therefore, there is a need to develop future therapeutic options which are safe and effective to control the inflammatory process. This review focuses in a method for the administration of fecal matters (which contains a mixture of various commensals) from a healthy donor to the inflamed colon called fecal microbiota transplantation (FMT) aiming to correct the underlying dysbiosis in the gut as one of the major driving force for the inflammatory process. IBD patients have reduced number of protective (e.g., clostridia and bacteroids) and increased number of pathogenic (e.g., adhesive invasive E. coli and mycobacterium avium paratuberculosis) commensals, and this method is aimed to shift these changes in the gut. Recent studies from animal models and clinical trials suggest promising effects of this method in treating patients with IBD, but more studies are urgently needed to confirm its efficacy and safety, since the etiology of this chronic inflammatory disease is not fully understood and caution should be taken when transplanting fecal matters between individuals which might transfer other infectious organisms and diseases.
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Affiliation(s)
- Maitham Abbas Khajah
- a Pharmacology & Therapeutics, Faculty of Pharmacy , Kuwait University , Kuwait , Kuwait
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Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is currently being established as a second-line treatment for recurrent Clostridium difficile infection. FMT is further being considered for other infectious and inflammatory conditions. Safe and reproducible methods for donor screening, laboratory processing and clinical application of FMT are warranted. METHODS Here, we describe the development of a complete clinical application framework for FMT. The framework has been developed to comply with the European Tissue Act, thus considering donor faeces for FMT comparable to a human tissue and not a drug. RESULTS Recruitment and screening of potential faeces donors took place in the public blood donor setting and consisted of questionnaires, blood sampling and faecal sample analysis. Once approved, and following their written informed consent, eligible donors were invited for voluntary faecal donation. Laboratory processing protocols describe the initial handling, cryopreservation and thawing for clinical application. The clinical FMT procedures took place in a gastroenterological setting using a nasojejunal tube or colonoscopy, and follow-ups were performed at 1, 8 and 26 weeks after FMT. Complete traceability of essential equipment, faecal samples and donor-recipient matching data will be maintained and secured for 30 years. CONCLUSION A clinical FMT service should be consolidated by a complete documentation system that complies with the European Tissue Act. In this paper, we provide a description of such a framework.
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Outcomes of Fecal Microbiota Transplantation for Clostridium difficile Infection in Patients with Inflammatory Bowel Disease. Dig Dis Sci 2017; 62:2870-2875. [PMID: 28451916 DOI: 10.1007/s10620-017-4580-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 04/12/2017] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND AIMS Fecal microbiota transplantation (FMT) has recently been shown to be a promising therapy for recurrent and refractory Clostridium difficile infections (CDI) despite lack of protocol standardization. Patients with inflammatory bowel disease (IBD) present a particular challenge to CDI therapy as they are reported to have worse clinical outcomes, including higher colectomy rates and increased mortality. We aimed to assess the outcomes of FMT for recurrent CDI in patients with IBD at our healthcare system. METHODS We constructed a retrospective cohort of all patients who underwent FMT at our healthcare system between December 2012 and May 2014. Patients with concurrent IBD were identified. We evaluated the differences in demographic and clinical characteristics, along with the outcomes to FMT between patients with IBD as compared to the general population. RESULTS Over the study period, 201 patients underwent FMT of which 20 patients had concurrent IBD. Patients with IBD were younger but did not differ from the general population in terms of CDI risk factors or disease severity. The response to FMT and rate of CDI relapse in the IBD group were not statistically different compared to the rest of the cohort. The overall response rate in the IBD population was 75% at 12 weeks. Of the patients who failed FMT 4 of 5 patients had active or untreated IBD. CONCLUSION Fecal microbiota transplantation provides a good alternative treatment option with high success rates for recurrent or refractory Clostridium difficile infection in patients with well-controlled IBD who fail standard antimicrobial therapy.
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Abstract
OPINION STATEMENT PURPOSE OF REVIEW: This article will review current literature describing fecal microbiota transplantation (FMT) in the treatment of various diseases, and its potential role in elderly patients (age ≥ 65 years). RECENT FINDINGS Research on FMT has blossomed in the last decade and its pivotal role in the treatment of recurrent Clostridium difficile infection (CDI) has been recognized by the American College of Gastroenterology in the latest guidelines. There is also emerging evidence that FMT may be beneficial in the treatment of severe and/or complicated CDI refractory to medical therapy, resulting in decreased rates of colectomy and mortality. In the elderly, CDI is associated with markedly higher rates of mortality and colectomy; outcomes are even worse when patients have underlying inflammatory bowel disease (IBD). While the majority of patients who receive FMT for CDI are older, only a handful of studies focused specifically on FMT treatment outcomes and safety in this age group. Current data corroborate the efficacy and safety profile of FMT, while also supporting its use for recurrent, severe, and/or complicated CDI in the elderly population. FMT is recommended for the treatment of recurrent, severe, and/or complicated CDI in patients older than 65 years of age. It may be prudent to offer FMT earlier in the disease course, possibly after just the second recurrence and for the first episode of severe CDI to avert complications including colectomy and end-organ failure that elderly patients are more prone to developing.
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Ma Y, Yang J, Cui B, Xu H, Xiao C, Zhang F. How Chinese clinicians face ethical and social challenges in fecal microbiota transplantation: a questionnaire study. BMC Med Ethics 2017; 18:39. [PMID: 28569156 PMCID: PMC5452366 DOI: 10.1186/s12910-017-0200-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 05/24/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is reportedly the most effective therapy for relapsing Clostridium Difficile infection (CDI) and a potential therapeutic option for many diseases. It also poses important ethical concerns. This study is an attempt to assess clinicians' perception and attitudes towards ethical and social challenges raised by fecal microbiota transplantation. METHODS A questionnaire was developed which consisted of 20 items: four items covered general aspects, nine were about ethical aspects such as informed consent and privacy issues, four concerned social and regulatory issues, and three were about an FMT bank. This was distributed to participants at the Second China gastroenterology and FMT conference in May 2015. Basic descriptive statistical analyses and simple comparative statistical tests were performed. RESULTS Nearly three quarters of the 100 respondents were gastro-enterologist physicians. 89% of all respondents believed FMT is a promising treatment modality for some diseases and 88% of whom chose clinical efficacy as the primary reason for recommending FMT. High expectation from patients and pressure on clinicians (33%) was reported as the most frequent reasons for not recommending FMT. The clinicians who had less familiarity with FMT reported significantly more worry related to the dignity and psychological impact of FMT compared to those who have high familiarity with FMT (51.6% vs 27.8%, p = 0.021).More than half of the respondents (56.1%) were concerned about the commercialization of FMT, although almost one in five respondents did not see this as a problem. CONCLUSIONS We found most respondents have positive attitudes towards FMT but low awareness of published evidence. Informed consent for vulnerable patients, privacy and protection of donors were perceived as the most challenging ethical aspects of FMT. This study identified areas of limited knowledge and ways of addressing ethical issues and indicates the need to devise the education and training for clinicians on FMT.
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Affiliation(s)
- Yonghui Ma
- Center for Bioethics, Medical College, Xiamen University, Xiamen, China
| | - Jinqiu Yang
- Department of Nursing, Medical College, Xiamen University, Xiamen, China
| | - Bota Cui
- Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hongzhi Xu
- Department of Gastroenterology, Xiamen Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
| | - Chuanxing Xiao
- Department of Gastroenterology, Xiamen Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Ma Y, Liu J, Rhodes C, Nie Y, Zhang F. Ethical Issues in Fecal Microbiota Transplantation in Practice. THE AMERICAN JOURNAL OF BIOETHICS : AJOB 2017; 17:34-45. [PMID: 28430065 DOI: 10.1080/15265161.2017.1299240] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Fecal microbiota transplantation (FMT) has demonstrated efficacy and is increasingly being used in the treatment of patients with recurrent Clostridium difficile infection. Despite a lack of high-quality trials to provide more information on the long-term effects of FMT, there has been great enthusiasm about the potential for expanding its applications. However, FMT presents many serious ethical and social challenges that must be addressed as part of a successful regulatory policy response. In this article, we draw on a sample of the scientific and bioethics literatures to examine clusters of ethical and social issues arising in five main areas: (1) informed consent and the vulnerability of patients; (2) determining what a "suitable healthy donor" is; (3) safety and risk; (4) commercialization and potential exploitation of vulnerable patients; and (5) public health implications. We find that these issues are complex and worthy of careful consideration by health care professionals. Desperation of a patient should not be the basis for selecting treatment with FMT, and the patient's interests should always be of paramount concern. Authorities must prioritize development of appropriate and effective regulation of FMT to safeguard patients and donors, promote further research into safety and efficacy, and avoid abuse of the treatment.
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Affiliation(s)
| | | | | | | | - Faming Zhang
- e Second Affiliated Hospital of Nanjing Medical University
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Weingarden AR, Vaughn BP. Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease. Gut Microbes 2017; 8:238-252. [PMID: 28609251 PMCID: PMC5479396 DOI: 10.1080/19490976.2017.1290757] [Citation(s) in RCA: 314] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a complex set of diseases that lead to chronic inflammation in the gastrointestinal tract. Although the etiology of IBD is not fully understood, it is well-known that the intestinal microbiota is associated with the development and maintenance of IBD. Manipulation of the gut microbiota, therefore, may represent a target for IBD therapy. Fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor is transplanted into a patient's GI tract, is already a successful therapy for Clostridium difficile infection. FMT is currently being explored as a potential therapy for IBD as well. In this review, the associations between the gut microbiota and IBD and the emerging data on FMT for IBD will be discussed.
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Affiliation(s)
- Alexa R. Weingarden
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
| | - Byron P. Vaughn
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA,CONTACT Byron P. Vaughn 420 Delaware street SE, MMC36, Minneapolis, MN 55455
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Bibbò S, Dore MP, Pes GM, Delitala G, Delitala AP. Is there a role for gut microbiota in type 1 diabetes pathogenesis? Ann Med 2017; 49:11-22. [PMID: 27499366 DOI: 10.1080/07853890.2016.1222449] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by insufficient insulin production due to the destruction of insulin secreting β-cells in the Langerhans islets. A variety of factors, including chemicals, viruses, commensal bacteria and diet have been proposed to contribute to the risk of developing the disorder. In the last years, gut microbiota has been proposed as a main factor in T1D pathogenesis. Several alterations of gut microbiota composition were described both in animal model and in humans. The decrease of Firmicutes/Bacteroides ratio was the most frequent pattern described, in particular, in human studies. Furthermore, Bacteroides, Clostridium cluster XIVa, Lactobacillus, Bifidobacterium, and Prevotella relative abundances were different in healthy and affected subjects. Dysbiosis would seem to increase intestinal permeability and thus promote the development of a pro-inflammatory niche that stimulates β-cell autoimmunity in predisposed subjects. Preliminary studies on animal models were realized to investigate the role of gut microbiota modulation as therapy or prevention approach in predisposed animals: promising and stimulating results have been reported. Key message Dietary antigens and microbiota-derived products might act as triggers of T1D by causing a pro-inflammatory and metabolic dysfunctional environment.
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Affiliation(s)
- Stefano Bibbò
- a Department of Clinical and Experimental Medicine , University of Sassari , Sassari , Italy
| | - Maria Pina Dore
- a Department of Clinical and Experimental Medicine , University of Sassari , Sassari , Italy
| | - Giovanni Mario Pes
- a Department of Clinical and Experimental Medicine , University of Sassari , Sassari , Italy
| | - Giuseppe Delitala
- a Department of Clinical and Experimental Medicine , University of Sassari , Sassari , Italy
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