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Voziki A, Deda O, Kachrimanidou M. The Efficacy of Fecal Microbiota Transplantation in Mouse Models Infected with Clostridioides difficile from the Perspective of Metabolic Profiling: A Systematic Review. Metabolites 2024; 14:677. [PMID: 39728458 DOI: 10.3390/metabo14120677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/07/2024] [Accepted: 11/26/2024] [Indexed: 12/28/2024] Open
Abstract
Objectives: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI) in mouse models using a metabolomics-based approach. Methods: A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed. Results: These studies consistently showed that FMT effectively restored gut microbiota and altered metabolic profiles, particularly increasing short-chain fatty acids (SCFAs) and secondary bile acids, which inhibited C. difficile growth. FMT proved superior to antibiotic and probiotic treatments in re-establishing a healthy gut microbiome, as evidenced by significant changes in the amino acid and carbohydrate levels. Despite its promise, variability in the outcomes-due to factors such as immune status, treatment protocols, and donor microbiome differences-underscores the need for standardization. Rather than pursuing immediate standardization, the documentation of factors such as donor and recipient microbiome profiles, preparation methods, and administration details could help identify optimal configurations for specific contexts and patient needs. In all the studies, FMT was successful in restoring the metabolic profile in mice. Conclusions: These findings align with the clinical data from CDI patients, suggesting that FMT holds potential as a therapeutic strategy for gut health restoration and CDI management. Further studies could pave the way for adoption in clinical practice.
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Affiliation(s)
- Anna Voziki
- Department of Microbiology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Olga Deda
- Laboratory of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
- Biomic AUTh, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center B1.4, 10th km Thessaloniki-Thermi Rd., 57001 Thessaloniki, Greece
| | - Melania Kachrimanidou
- Department of Microbiology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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Khanna S. Microbiota restoration for recurrent Clostridioides difficile infection. Panminerva Med 2024; 66:417-426. [PMID: 39382853 DOI: 10.23736/s0031-0808.24.05111-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.
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Affiliation(s)
- Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA -
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Salahi A, Abd El-Ghany WA. Beyond probiotics, uses of their next-generation for poultry and humans: A review. J Anim Physiol Anim Nutr (Berl) 2024; 108:1336-1347. [PMID: 38689488 DOI: 10.1111/jpn.13972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 04/03/2024] [Accepted: 04/13/2024] [Indexed: 05/02/2024]
Abstract
The production of healthy food is one of the basic requirements and challenges. Research efforts have been introduced in the human's food industry to reduce the microbial resistance and use safe and healthy alternatives with a high durability. However, the conducted work about these issues in the field of livestock animal production have been started since 2015. Inappropriate and extensive use of antibiotics has resulted in the increase of antimicrobial resistance, presence of drug residues in tissues, and destruction of the gut microbiome. Therefore, discovering and developing antibiotic substitutes were urgent demands. Probiotic compounds containing living micro-organisms are important antibiotic alternative that have been beneficially and extensively used in humans, animals, and poultry. However, some probiotics show some obstacles during production and applications. Accordingly, this review article proposes a comprehensive description of the next-generation of probiotics including postbiotics, proteobiotics, psychobiotics, immunobiotics and paraprobiotics and their effects on poultry production and human's therapy. These compounds proved great efficiency in terms of restoring gut health, improving performance and general health conditions, modulating the immune response and reducing the pathogenic micro-organisms. However, more future research work should be carried out regarding this issue.
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Affiliation(s)
- Ahmad Salahi
- Department of Animal Science, Faculty of Agriculture, Zanjan University, Zanjan, Iran
| | - Wafaa A Abd El-Ghany
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
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Wei X, Qian S, Yang Y, Mo J. Microbiome-based therapies for periodontitis and peri-implantitis. Oral Dis 2024; 30:2838-2857. [PMID: 37890080 DOI: 10.1111/odi.14782] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 09/16/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023]
Abstract
OBJECTIVES Periodontitis and peri-implantitis are oral infectious-inflammatory diseases associated with oral microbial dysbiosis. Microbiome-based therapies, characterized by manipulation of the microbiota, are emerging as promising therapeutic approaches to resolve the microbial dysbiosis and associated dysregulation of immune system. This review aims at summarizing recent progress on microbiome-based therapies in periodontitis and peri-implantitis, promoting a further understanding of the related therapeutic mechanisms. SUBJECTS AND METHODS Pertinent literatures focused on microbiome-based therapies for periodontitis and peri-implantitis are obtained from PubMed and Web of Science. RESULTS In this article, we review the roles and therapeutic mechanisms of four microbiome-based therapies, including probiotics, postbiotics, predatory bacteria and phages, and microbiota transplantation, in the management of periodontitis and peri-implantitis. Challenges facing this field are also discussed, highlighting the areas that require more attention and investigation. CONCLUSIONS Microbiome-based therapies may serve as effective treatment for periodontitis and peri-implantitis. This review presents a new viewpoint to this field.
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Affiliation(s)
- Xindi Wei
- Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
| | - Shujiao Qian
- Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
| | - Yijie Yang
- Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
| | - Jiaji Mo
- Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
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Kasapoglu M, Yadavalli R, Nawaz S, Althwanay A, AlEdani EM, Kaur H, Butt S. The Impact of Microbiome Interventions on the Progression and Severity of Inflammatory Bowel Disease: A Systematic Review. Cureus 2024; 16:e60786. [PMID: 38779440 PMCID: PMC11110475 DOI: 10.7759/cureus.60786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 05/21/2024] [Indexed: 05/25/2024] Open
Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation. The dysbiotic gut microbiome likely contributes to IBD pathogenesis. Microbiome-directed therapies such as fecal microbiota transplantation (FMT), probiotics, and synbiotics may help induce and maintain remission. This systematic review aimed to determine the efficacy of microbiome interventions compared to standard therapy or placebo for IBD treatment. PubMed, EMBASE, Cochrane CENTRAL, and Web of Science were searched for randomized controlled trials on microbiome interventions in IBD from inception to October 2023. The risk of bias was assessed using Cochrane tools. Outcomes included disease activity, endoscopy, histology, quality of life, and adverse events. A total of 18 randomized controlled trials were included. Three trials found intensive (i.e., high frequency of administration and/or large volumes of fecal material) multi-donor FMT superior to autologous FMT or glucocorticoids for UC remission induction. Seven placebo-controlled trials demonstrated higher remission rates with FMT, especially intensive protocols, versus control for mild-to-moderate UC. However, a single FMT did not prevent relapses. Seven probiotic trials showed the potential to improve UC activity and maintain remission. One synbiotic trial reported reduced inflammation and symptoms versus placebo. Serious adverse events were rare. Small sample sizes and protocol heterogeneity limited the conclusions. Current evidence indicates the potential benefits of microbiome interventions, particularly intensive multi-donor FMT, for inducing and maintaining remission in UC. Probiotics may also improve outcomes. Adequately powered trials using standardized protocols are still needed to firmly establish efficacy and safety. Microbiome-directed therapies represent a promising approach for improving IBD outcomes.
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Affiliation(s)
- Malik Kasapoglu
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Rajesh Yadavalli
- Internal Medicine, Rajiv Gandhi Institute of Medical Sciences, Adilabad, IND
| | - Sarosh Nawaz
- Psychiatry, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Abdulaziz Althwanay
- Dermatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Medicine, Imam Abdulrahman Bin Faisal University, Dammam, SAU
| | - Esraa M AlEdani
- Dermatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Harleen Kaur
- Medicine and Surgery, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, IND
| | - Samia Butt
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Stallmach A, von Müller L, Storr M, Link A, Konturek PC, Solbach PC, Weiss KH, Wahler S, Vehreschild MJGT. [Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:490-499. [PMID: 37187187 DOI: 10.1055/a-2075-2725] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
INTRODUCTION Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far. MATERIAL AND METHODOLOGY Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation. RESULTS Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%. DISCUSSION In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.
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Affiliation(s)
- Andreas Stallmach
- Klinik für Innere Medizin IV, Universitätsklinikum Jena, Jena, Deutschland
| | | | | | - Alexander Link
- Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Deutschland
| | - Peter C Konturek
- Thüringen-Klinik Saalfeld Georgius Agricola GmbH, Saalfeld, Deutschland
| | | | - Karl Heinz Weiss
- Krankenhaus Salem der Evang. Stadtmission Heidelberg gGmbH, Heidelberg, Deutschland
| | | | - Maria J G T Vehreschild
- Medizinische Klinik 2, Infektiologie, Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland
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Wang M, Song Z, Lai S, Tang F, Dou L, Yang F. Depression-associated gut microbes, metabolites and clinical trials. Front Microbiol 2024; 15:1292004. [PMID: 38357350 PMCID: PMC10864537 DOI: 10.3389/fmicb.2024.1292004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 01/16/2024] [Indexed: 02/16/2024] Open
Abstract
Depression is one of the most prevalent mental disorders today. Over the past decade, there has been considerable attention given to the field of gut microbiota associated with depression. A substantial body of research indicates a bidirectional communication pathway between gut microbiota and the brain. In this review, we extensively detail the correlation between gut microbiota, including Lactobacillus acidophilus and Bifidobacterium longum, and metabolites such as short-chain fatty acids (SCFAs) and 5-hydroxytryptamine (5-HT) concerning depression. Furthermore, we delve into the potential health benefits of microbiome-targeted therapies, encompassing probiotics, prebiotics, and synbiotics, in alleviating depression. Lastly, we underscore the importance of employing a constraint-based modeling framework in the era of systems medicine to contextualize metabolomic measurements and integrate multi-omics data. This approach can offer valuable insights into the complex metabolic host-microbiota interactions, enabling personalized recommendations for potential biomarkers, novel drugs, and treatments for depression.
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Affiliation(s)
- Meiling Wang
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
| | - Zhaoqi Song
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
| | - Shirong Lai
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
| | - Furong Tang
- Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
| | - Lijun Dou
- Genomic Medicine Institute, Lerner Research Institute, Cleveland, OH, United States
| | - Fenglong Yang
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
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Porcari S, Maida M, Bibbò S, McIlroy J, Ianiro G, Cammarota G. Fecal Microbiota Transplantation as Emerging Treatment in European Countries 2.0. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1435:85-99. [PMID: 38175472 DOI: 10.1007/978-3-031-42108-2_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections and one of the leading causes of morbidity and mortality in hospitalized patients in the world. Although several antibiotics effectively treat CDI, some individuals may not respond to these drugs and may be cured by transplanting stool from healthy donors. FMT has demonstrated extraordinary cure rates for the cure of CDI recurrences.Moreover, FMT has also been investigated in other disorders associated with the alteration of gut microbiota, such as inflammatory bowel disease (IBD), where the alterations of the gut microbiota ecology have been theorized to play a causative role. Although FMT is currently not recommended to cure IBD patients in clinical practice, several studies have been recently carried out with the ultimate goal to search new therapeutic options to patients.This review summarizes data on the use of FMT for the treatment of both CDI and IBD, with a special attention to highlight studies conducted in European countries.
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Affiliation(s)
- Serena Porcari
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital, Caltanissetta, Italy
| | - Stefano Bibbò
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - James McIlroy
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK
| | - Gianluca Ianiro
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
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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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Xin Y, Huang C, Zheng M, Zhou W, Zhang B, Zhao M, Lu Q. Fecal microbiota transplantation in the treatment of systemic lupus erythematosus: What we learnt from the explorative clinical trial. J Autoimmun 2023; 141:103058. [PMID: 37179170 DOI: 10.1016/j.jaut.2023.103058] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 04/26/2023] [Accepted: 05/03/2023] [Indexed: 05/15/2023]
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease with the characterized presence of autoantibodies and resulting in multiple organ damage, which is incurable and can be lethal. The current treatments are limited and less progress has been made in drug discovery for the last few decades. Researches imply that gut dysbiosis exists in both patients and murine models with SLE, taking part in the pathogenesis of SLE through multiple mechanisms such as microbiota translocation and molecular mimicry. Intestinal interventions on the gut microbiome by fecal transplantations to reconstitute the gut-immunity homeostasis serve as a novel therapeutic option for SLE patients. Fecal microbiota transplantation (FMT), which is usually used in intestinal diseases, has been firstly demonstrated to be safe and efficient in recovering gut microbiota structure of SLE patients and reducing lupus activity in our recent clinical trial, which is the first trial testing FMT therapy in SLE treatment. In this paper, we reviewed the results of the single-arm clinical trial and made recommendations on FMT practice in SLE treatment including therapeutic indications, screening items and dosage regimen, trying to provide references for future study and clinical practice. We also came up with the unanswered questions that need to be solved by the ongoing randomized controlled trial as well as the future expectations for the intestinal intervention strategies of SLE patients.
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Affiliation(s)
- Yue Xin
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Cancan Huang
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Meiling Zheng
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Wenhui Zhou
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Bo Zhang
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Ming Zhao
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
| | - Qianjin Lu
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
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11
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Zhang X, Luo X, Tian L, Yue P, Li M, Liu K, Zhu D, Huang C, Shi Q, Yang L, Xia Z, Zhao J, Ma Z, Li J, Leung JW, Lin Y, Yuan J, Meng W, Li X, Chen Y. The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review. Front Microbiol 2023; 14:1286429. [PMID: 38029189 PMCID: PMC10655098 DOI: 10.3389/fmicb.2023.1286429] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
Background Gut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear. Methods The gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226). Results Gut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88-97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn's disease but low to very low quality for other diseases. Conclusion Gut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT.
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Affiliation(s)
- Xianzhuo Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Xufei Luo
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Liang Tian
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Ping Yue
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Mengyao Li
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Kefeng Liu
- Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Daoming Zhu
- Department of Radiology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Chongfei Huang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Qianling Shi
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Liping Yang
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zhili Xia
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Jinyu Zhao
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Zelong Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Jianlong Li
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Joseph W. Leung
- Division of Gastroenterology and Hepatology, UC Davis Medical Center and Sacramento VA Medical Center, Sacramento, CA, United States
| | - Yanyan Lin
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Jinqiu Yuan
- Clinical Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Wenbo Meng
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xun Li
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yaolong Chen
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Institute of Health Data Science, Lanzhou University, Lanzhou, China
- WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China
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12
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Berry P, Khanna S. Recurrent Clostridioides difficile Infection: Current Clinical Management and Microbiome-Based Therapies. BioDrugs 2023; 37:757-773. [PMID: 37493938 DOI: 10.1007/s40259-023-00617-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2023] [Indexed: 07/27/2023]
Abstract
Clostridioides difficile is one of the most important causes of healthcare-associated diarrhea. The high incidence and recurrence rates of C. difficile infection, as well as its associated morbidity and mortality, are great concerns. The most common complication of C. difficile infection is recurrence, with rates of 20-30% after a primary infection and 60% after three or more episodes. Medical management of recurrent C. difficile infection involves a choice of therapy that is different from the antibiotic used in the primary episode. Patients with recurrent C. difficile infection also benefit from fecal microbiota transplantation or standardized microbiome restoration therapies (approved or experimental) to restore eubiosis. In contrast to antibiotics, microbiome restoration therapies restore a normal gut flora and eliminate C. difficile colonization and infection. Fecal microbiota transplantation in recurrent C. difficile infection has demonstrated higher success rates than vancomycin, fidaxomicin, or placebo. Fecal microbiota transplantation has traditionally been considered safe, with the most common adverse reactions being abdominal discomfort, and diarrhea, and rare serious adverse events. Significant heterogeneity and a lack of standardization regarding the process of preparation, and administration of fecal microbiota transplantation remain a major pitfall. Standardized microbiome-based therapies provide a promising alternative. In the ECOSPOR III trial of SER-109, an oral formulation of bacterial spores, a significant reduction in the recurrence rate (12%) was observed compared with placebo (40%). In the phase III PUNCH CD3 trial, RBX2660 also demonstrated high efficacy rates of 70.6% versus 57.5%. Both these agents are now US Food and Drug Administration approved for recurrent C. difficile infection. Other standardized microbiome-based therapies currently in the pipeline are VE303, RBX7455, and MET-2. Antibiotic neutralization strategies, vaccines, passive monoclonal antibodies, and drug repurposing are other therapeutic strategies being explored to treat C. difficile infection.
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Affiliation(s)
- Parul Berry
- All India Institute of Medical Sciences, New Delhi, India
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, C. difficile Clinic and Microbiome Restoration Program, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
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13
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Wu X, Ai RJ, Xu J, Wen Q, Pan HQ, Zhang ZH, Ning W, Fang Y, Ding DF, Wang Q, Han S, Liu X, Wu M, Jia ZY, Jia S, Lin T, Cui BT, Nie YZ, Wang X, Zhang FM. Washed microbiota transplantation for Clostridioides difficile infection: A national multicenter real-world study. J Dig Dis 2023; 24:540-549. [PMID: 37681235 DOI: 10.1111/1751-2980.13227] [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: 05/05/2023] [Revised: 08/21/2023] [Accepted: 09/06/2023] [Indexed: 09/09/2023]
Abstract
OBJECTIVES Fecal microbiota transplantation (FMT) has been recommended for the treatment of recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the therapeutic efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings. METHODS This multicenter real-world cohort study included CDI patients undergoing WMT. The primary outcome was the clinical cure rate of CDI within 8 weeks after WMT. Secondary outcomes included the CDI recurrence rate and reduction in total abdominal symptom score (TASS) during the follow-up period. Adverse events related to WMT were recorded. RESULTS Altogether 90.7% (49/54) of CDI patients achieved clinical cure after treated with WMT. The cure rate was 83.3% for cases with severe and complicated CDI (ScCDI) (n = 30) and 100% for non-ScCDI cases (n = 24) (P = 0.059). No difference was observed in the clinical cure rate between patients with first and recurrent CDI (91.9% vs 88.2%, P = 0.645). One week post-WMT, TASS showed a remarkable decrease compared to that at baseline (P < 0.001). Totally, 8.2% (4/49) of patients suffered CDI recurrence during the follow-up period. A WHO performance score of 4, age ≥65 years, higher TASS score, and higher Charlson comorbidity index score were potential risk factors for efficacy (P = 0.018, 0.03, 0.01, 0.034, respectively). Four (3.8%) transient adverse events related to WMT were observed. CONCLUSIONS This study emphasizes the attractive value of WMT for CDI. Early WMT may be recommended for CDI, especially for those in serious condition or with complex comorbidities. TRIAL REGISTRATION ClinicalTrials.gov, no. NCT03895593 (registered on 27 March 2019).
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Affiliation(s)
- Xia Wu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Ru Jun Ai
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Jie Xu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Quan Wen
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Hua Qin Pan
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Zhi Hua Zhang
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Wang Ning
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
| | - Ying Fang
- Department of Gastroenterology, The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Da Fa Ding
- Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Quan Wang
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Shuang Han
- Department of Gastroenterology, Honghui Hospital, Xi'an, Shaanxi Province, China
| | - Xiao Liu
- Department of Gastroenterology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi Province, China
| | - Mei Wu
- Department of Gastroenterology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China
| | - Zhen Yu Jia
- Department of General Practice, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Song Jia
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Tao Lin
- Department of Gastroenterology, Xi'an Daxing Hospital, Xi'an, Shaanxi Province, China
| | - Bo Ta Cui
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yong Zhan Nie
- Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, China
- National Clinical Research Center for Digestive Diseases, Xi'an, Shaanxi Province, China
| | - Xin Wang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
- National Clinical Research Center for Digestive Diseases, Xi'an, Shaanxi Province, China
| | - Fa Ming Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
- National Clinical Research Center for Digestive Diseases, Xi'an, Shaanxi Province, China
- Division of Microbiotherapy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
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14
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Wortelboer K, de Jonge PA, Scheithauer TPM, Attaye I, Kemper EM, Nieuwdorp M, Herrema H. Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety. Nat Commun 2023; 14:5600. [PMID: 37699894 PMCID: PMC10497675 DOI: 10.1038/s41467-023-41329-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 08/24/2023] [Indexed: 09/14/2023] Open
Abstract
Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies have shown that faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with metabolic syndrome were randomised to a faecal filtrate transplantation (FFT) from a lean healthy donor (n = 12) or placebo (n = 12). The primary outcome, change in glucose metabolism, and secondary outcomes, safety and longitudinal changes within the intestinal bacteriome and phageome, were assessed from baseline up to 28 days. All 24 included subjects completed the study and are included in the analyses. While the overall changes in glucose metabolism are not significantly different between both groups, the FFT is well-tolerated and without any serious adverse events. The phage virion composition is significantly altered two days after FFT as compared to placebo, which coincides with more virulent phage-microbe interactions. In conclusion, we provide evidence that gut phages can be safely administered to transiently alter the gut microbiota of recipients.
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Affiliation(s)
- Koen Wortelboer
- Amsterdam UMC location University of Amsterdam, Experimental Vascular Medicine, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, metabolism and nutrition, Amsterdam, The Netherlands
| | - Patrick A de Jonge
- Amsterdam UMC location University of Amsterdam, Experimental Vascular Medicine, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, metabolism and nutrition, Amsterdam, The Netherlands
| | - Torsten P M Scheithauer
- Amsterdam UMC location University of Amsterdam, Experimental Vascular Medicine, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, metabolism and nutrition, Amsterdam, The Netherlands
| | - Ilias Attaye
- Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, metabolism and nutrition, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Vascular Medicine, Amsterdam, The Netherlands
| | - E Marleen Kemper
- Amsterdam UMC location University of Amsterdam, Experimental Vascular Medicine, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Department of Pharmacy and Clinical Pharmacology, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Amsterdam UMC location University of Amsterdam, Experimental Vascular Medicine, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, metabolism and nutrition, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Vascular Medicine, Amsterdam, The Netherlands
- Amsterdam UMC location Vrije University Medical Center, Department of Internal Medicine, Diabetes Center, Amsterdam, The Netherlands
| | - Hilde Herrema
- Amsterdam UMC location University of Amsterdam, Experimental Vascular Medicine, Amsterdam, The Netherlands.
- Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, The Netherlands.
- Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, metabolism and nutrition, Amsterdam, The Netherlands.
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van Praagh J, Havenga K. What Is the Microbiome? A Description of a Social Network. Clin Colon Rectal Surg 2023; 36:91-97. [PMID: 36844706 PMCID: PMC9946720 DOI: 10.1055/s-0043-1760863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
The gut microbiome has coevolved with its hosts over the years, forming a complex and symbiotic relationship. It is formed by what we do, what we eat, where we live, and with whom we live. The microbiome is known to influence our health by training our immune system and providing nutrients for the human body. However, when the microbiome becomes out of balance and dysbiosis occurs, the microorganisms within can cause or contribute to diseases. This major influencer on our health is studied intensively, but it is unfortunately often overlooked by the surgeon and in surgical practice. Because of that, there is not much literature about the microbiome and its influence on surgical patients or procedures. However, there is evidence that it plays a major role, showing that it needs to be a topic of interest for the surgeon. This review is written to show the surgeon the importance of the microbiome and why it should be taken into consideration when preparing or treating patients.
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Affiliation(s)
- J.B. van Praagh
- Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Klaas Havenga
- Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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16
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Chandra H, Kovall RA, Yadav JS, Sun X. Host Immune Responses to Surface S-Layer Proteins (SLPs) of Clostridioides difficile. Microorganisms 2023; 11:380. [PMID: 36838345 PMCID: PMC9963625 DOI: 10.3390/microorganisms11020380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Revised: 01/28/2023] [Accepted: 02/01/2023] [Indexed: 02/05/2023] Open
Abstract
Clostridioides difficile, a nosocomial pathogen, is an emerging gut pathobiont causing antibiotic-associated diarrhea. C. difficile infection involves gut colonization and disruption of the gut epithelial barrier, leading to the induction of inflammatory/immune responses. The expression of two major exotoxins, TcdA and TcdB is the major cause of C. difficile pathogenicity. Attachment of bacterial abundant cell wall proteins or surface S-layer proteins (SLPs) such as SlpA with host epithelial cells is critical for virulence. In addition to being toxins, these surface components have been shown to be highly immunogenic. Recent studies indicate that C. difficile SLPs play important roles in the adhesion of the bacteria to the intestinal epithelial cells, disruption of tight junctions, and modulation of the immune response of the host cells. These proteins might serve as new targets for vaccines and new therapeutic agents. This review summarizes our current understanding of the immunological role of SLPs in inducing host immunity and their use in the development of vaccines and novel therapeutics to combat C. difficile infection.
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Affiliation(s)
- Harish Chandra
- Department of Environmental Microbiology, School of Earth and Environmental Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow 226025, UP, India
- Department of Molecular and Cellular Biosciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Rhett A. Kovall
- Department of Molecular and Cellular Biosciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Jagjit S. Yadav
- Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Xingmin Sun
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
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17
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Fecal Microbiota Transplantation Research over the Past Decade: Current Status and Trends. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2023; 2023:6981721. [PMID: 36654766 PMCID: PMC9842422 DOI: 10.1155/2023/6981721] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/28/2022] [Accepted: 12/29/2022] [Indexed: 01/11/2023]
Abstract
Background Fecal microbiota transplantation (FMT) is a current research hotspot, with a surge in the output of publications over the past decade. This study dedicates to the exploration of the research status and highlights significant themes and future trends in FMT research with the aid of bibliometric analysis. Methods FMT publications from 2012 to 2021 were retrieved on August 12, 2022, using the SCI-Expanded of Web of Science (WoS). The Bibliometrix in R program, Microsoft Office Excel, VOSviewer, and CiteSpace were utilized for bibliometrics and visual analysis, revealing the main publications, journals, countries, agencies, authors, and keywords distribution in FMT research. Results There were 2,931 papers included. FMT research presented a growing trend from 2012 to 2021. The countries with the most publications and contributions in FMT area were China and the United States. The high-yield institutions were Harvard University, Udice French Research Universities, and the University of California System. The primary authors were Nieuwdorp Max, Allegretti Jessica R, and Kassam Zain. Frontiers in Microbiology and Science were the top-ranked journals in publications and total citations, respectively. The important topics primarily included FMT-related mechanisms and the usage of FMT in Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), metabolic disease, neurological disorders, and psychiatric disorders. Future research would primarily concentrate on neurological disorders, chemotherapy and immunotherapy for malignant tumors, and FMT-related consensus and guidelines. Conclusion With the help of bibliometric analysis, we were able to obtain the understanding of the status and trends of global FMT-related research. The field of FMT is undergoing tremendous progress, and our findings can guide clinical researchers' and practitioners' future work in the rapidly evolving field of FMT.
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18
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Tian H, Cui J, Ye C, Zhao J, Yang B, Xu Y, Ji S, Wang L, Lv X, Ma C, Zhou S, Li N, Wang X, Qin H, Chen Q. Depletion of butyrate-producing microbes of the Firmicutes predicts nonresponse to FMT therapy in patients with recurrent Clostridium difficile infection. Gut Microbes 2023; 15:2236362. [PMID: 37469017 PMCID: PMC10361143 DOI: 10.1080/19490976.2023.2236362] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 06/20/2023] [Accepted: 07/10/2023] [Indexed: 07/21/2023] Open
Abstract
Approximately 10% of individuals diagnosed with Clostridium difficile infection (CDI) show the resistance to fecal microbiota transplantation (FMT), with the underlying mechanisms remaining elusive. Deciphering the intricate microbiome profile within this particular subset of FMT-refractory patients via clinical FMT investigations assumes paramount importance, as it holds the key to designing targeted therapeutic interventions tailored for CDI, particularly recurrent CDI (rCDI). A cohort of twenty-three patients afflicted with rCDI, exhibiting congruent clinical baselines, was meticulously selected for FMT. Rigorous screening of thousands of healthy individuals identified ten FMT donors who met stringent health standards, while a total of 171 stool samples were collected to serve as healthy controls. To assess the influence of microbiome dynamics on FMT efficacy, fecal samples were collected from four donors over a continuous period of twenty-five weeks. After FMT treatment, seven individuals exhibited an inadequate response to FMT. These non-remission patients displayed a significant reduction in α-diversity indexes. Meanwhile, prior to FMT, the abundance of key butyrate-producing Firmicutes bacteria, including Christensenellaceae_R_7_group, Ruminococcaceae_unclassified, Coprococcus_2, Fusicatenibacter, Oscillospira, and Roseburia, were depleted in non-remission patients. Moreover, Burkholderiales_unclassified, Coprococcus_2, and Oscillospira failed to colonize non-remission patients both pre- and post-treatment. Conversely, patients with a favorable FMT response exhibited a higher relative abundance of Veillonella prior to treatment, whereas its depletion was commonly observed in non-remission individuals. Genera interactions in lower effectiveness FMT donors were more similar to those in non-remission patients, and Burkholderiales_unclassified, Coprococcus_2, and Oscillospira were frequently depleted in these lower effectiveness donors. Older patients were not conducive to the colonization of Veillonella, consistent with their poor prognosis after FMT. FMT non-remission rCDI patients exhibited distinct characteristics that hindered the colonization of beneficial butyrate-producing Firmicutes microbes. These findings hold promise in advancing the precision of FMT therapy for rCDI patients.
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Affiliation(s)
- Hongliang Tian
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Jiaqu Cui
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Chen Ye
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Jiangman Zhao
- Department of Bioinformatics, Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Bo Yang
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Yue Xu
- Department of Bioinformatics, Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Shushen Ji
- Department of Bioinformatics, Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Le Wang
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Xiaoqiong Lv
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Chunlian Ma
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Shailan Zhou
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Ning Li
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Xinjun Wang
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
- Research Institute of Intestinal Diseases, Tongji University School of Medicine, Shanghai, China
| | - Huanlong Qin
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
- Research Institute of Intestinal Diseases, Tongji University School of Medicine, Shanghai, China
| | - Qiyi Chen
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Clinical Research Center for Digestive Diseases, Tongji University, Shanghai, China
- Shanghai Institution of Gut Microbiota Research and Engineering Development, Tenth People’s Hospital of Tongji University, Shanghai, China
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Li Y, Cai H, Sussman DA, Donet J, Dholaria K, Yang J, Panara A, Croteau R, Barkin JS. Association Between Immunosuppressive Therapy and Outcome of Clostridioides difficile Infection: Systematic Review and Meta-Analysis. Dig Dis Sci 2022; 67:3890-3903. [PMID: 34554365 DOI: 10.1007/s10620-021-07229-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 08/11/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Patients with Clostridioides difficile infection (CDI) often have coexisting medical problems requiring immunosuppressive therapy. However, limited data are available on the association between immunosuppressive therapy and CDI outcomes. AIM To determine the association between immunosuppressive therapy and CDI outcomes. METHODS PubMed, Embase, and Cochrane Library were searched through February 2021. Two reviewers independently reviewed and included studies that compared adult CDI patients who received immunosuppressive therapy to those who did not. The primary outcome was complicated CDl, including death, surgery, shock, or ICU admission. Raw data or unadjusted odds ratios (ORs) were used to calculate pooled ORs with 95% confidence intervals (CIs). RESULTS Twenty-two studies with a total of 5759 CDI patients were selected. Immunosuppressive therapy was significantly associated with both primary outcome and death, with pooled ORs of 1.61 (95% CI 1.33-1.96) and 1.73 (95% CI 1.39-2.15) separately. The association between corticosteroids and primary outcome was also significant with OR of 1.73 (95% CI 1.41, 2.12). In subgroup analysis, the factors explaining differences in study results included study quality, patient age, and whether individual studies had adjusted for potential confounders. In a systematic review, most studies suggested a positive association between immunosuppressive therapy and complicated outcomes of CDI in patients comorbid for IBD. CONCLUSIONS Our systematic review and meta-analysis demonstrate that immunosuppressive therapy is a risk factor for complicated outcomes of CDI.
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Affiliation(s)
- Yiting Li
- Department of Internal Medicine, Saint Francis Medical Center, Trenton, NJ, USA
- Division of Gastroenterology and Hepatology, University of New Mexico, School of Medicine, Albuquerque, NM, USA
| | - Haifeng Cai
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, 325000, Zhejiang, China
| | - Daniel A Sussman
- Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
| | - Jean Donet
- Department of Gastroenterology and Hepatology, University of California, San Francisco, Fresno, CA, USA
| | | | - Jiajia Yang
- University of South Florida, Morsani College of Medicine, Tampa, FL, USA
| | - Ami Panara
- Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
| | - Ryan Croteau
- Department of Gastroenterology, Wellspan Digestive Health, York, PA, USA
| | - Jamie S Barkin
- Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA.
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20
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Kunishima H, Ohge H, Suzuki H, Nakamura A, Matsumoto K, Mikamo H, Mori N, Morinaga Y, Yanagihara K, Yamagishi Y, Yoshizawa S. Japanese Clinical Practice Guidelines for Management of Clostridioides (Clostridium) difficile infection. J Infect Chemother 2022; 28:1045-1083. [PMID: 35618618 DOI: 10.1016/j.jiac.2021.12.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/16/2021] [Accepted: 12/13/2021] [Indexed: 12/19/2022]
Affiliation(s)
- Hiroyuki Kunishima
- Department of Infectious Diseases, St. Marianna University School of Medicine, Japan.
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Japan
| | - Hiromichi Suzuki
- Division of Infectious Diseases, Department of Medicine, Tsukuba Medical Center Hospital, Japan
| | - Atsushi Nakamura
- Division of Infection Control and Prevention, Nagoya City University Hospital, Japan
| | - Kazuaki Matsumoto
- Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, Japan
| | - Hiroshige Mikamo
- Clinical Infectious Diseases, Graduate School of Medicine, Aichi Medical University, Japan
| | - Nobuaki Mori
- Division of General Internal Medicine and Infectious Diseases, National Hospital Organization Tokyo Medical Center, Japan
| | - Yoshitomo Morinaga
- Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Yuka Yamagishi
- Clinical Infectious Diseases, Graduate School of Medicine, Aichi Medical University, Japan
| | - Sadako Yoshizawa
- Department of Clinical Laboratory/Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Japan
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21
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Asadi A, Shadab Mehr N, Mohamadi MH, Shokri F, Heidary M, Sadeghifard N, Khoshnood S. Obesity and gut-microbiota-brain axis: A narrative review. J Clin Lab Anal 2022; 36:e24420. [PMID: 35421277 PMCID: PMC9102524 DOI: 10.1002/jcla.24420] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/19/2022] [Accepted: 03/29/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune‐neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut–brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms. Materials and methods Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies. Results The gut–brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus–pituitary–adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity. Conclusion This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.
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Affiliation(s)
- Arezoo Asadi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Negar Shadab Mehr
- Student Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | | | - Fazlollah Shokri
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran.,Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Nourkhoda Sadeghifard
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
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22
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Tixier EN, Verheyen E, Luo Y, Grinspan LT, Du CH, Ungaro RC, Walsh S, Grinspan AM. Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile. Dig Dis Sci 2022; 67:978-988. [PMID: 33748913 DOI: 10.1007/s10620-021-06908-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 02/19/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT) has proved to be a highly effective treatment for recurrent CDI, its efficacy in severe or fulminant CDI remains uncertain. AIMS To perform a systematic review with meta-analysis evaluating clinical outcomes and safety of FMT in severe and fulminant CDI. METHODS A systemic review with meta-analysis was performed through comprehensive search of Embase, Medline (Ovid), trial registers, and conference abstracts through January 2020. Studies on FMT in severe and fulminant CDI were included. Meta-analysis was done with random effects models given heterogeneity to estimate rates of cure, mortality, and colectomy. Publication bias was assessed using Egger's test. RESULTS Sixteen studies comprised of one randomized controlled trial, four cohort studies, and eleven case series were analyzed. In total, 676 patients underwent FMT for severe or fulminant CDI. The overall rate of clinical cure after single FMT was 61.3% (95% CI 43.2-78.0%) with 10.9% (95% CI 0.2-30.2%) of patients experiencing major adverse events. The overall pooled colectomy rate after FMT was 8.2% (95% CI 0.1-23.7%) with a pooled all-cause mortality rate after FMT of 15.6% (95% CI 7.8-25.0%). CONCLUSION Low-quality data support the use of fecal microbiota transplantation in patients with severe and fulminant Clostridioides difficile infection.
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Affiliation(s)
- Emily N Tixier
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Yuying Luo
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Charles H Du
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ryan C Ungaro
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Samantha Walsh
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ari M Grinspan
- Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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23
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Nibbering B, Gerding DN, Kuijper EJ, Zwittink RD, Smits WK. Host Immune Responses to Clostridioides difficile: Toxins and Beyond. Front Microbiol 2022; 12:804949. [PMID: 34992590 PMCID: PMC8724541 DOI: 10.3389/fmicb.2021.804949] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 11/22/2021] [Indexed: 12/17/2022] Open
Abstract
Clostridioides difficile is often resistant to the actions of antibiotics to treat other bacterial infections and the resulting C. difficile infection (CDI) is among the leading causes of nosocomial infectious diarrhea worldwide. The primary virulence mechanism contributing to CDI is the production of toxins. Treatment failures and recurrence of CDI have urged the medical community to search for novel treatment options. Strains that do not produce toxins, so called non-toxigenic C. difficile, have been known to colonize the colon and protect the host against CDI. In this review, a comprehensive description and comparison of the immune responses to toxigenic C. difficile and non-toxigenic adherence, and colonization factors, here called non-toxin proteins, is provided. This revealed a number of similarities between the host immune responses to toxigenic C. difficile and non-toxin proteins, such as the influx of granulocytes and the type of T-cell response. Differences may reflect genuine variation between the responses to toxigenic or non-toxigenic C. difficile or gaps in the current knowledge with respect to the immune response toward non-toxigenic C. difficile. Toxin-based and non-toxin-based immunization studies have been evaluated to further explore the role of B cells and reveal that plasma cells are important in protection against CDI. Since the success of toxin-based interventions in humans to date is limited, it is vital that future research will focus on the immune responses to non-toxin proteins and in particular non-toxigenic strains.
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Affiliation(s)
- Britt Nibbering
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Dale N Gerding
- Department of Veterans Affairs, Research Service, Edward Hines Jr. VA Hospital, Hines, IL, United States
| | - Ed J Kuijper
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Romy D Zwittink
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Wiep Klaas Smits
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
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24
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The interplay between Sleep and Gut Microbiota. Brain Res Bull 2022; 180:131-146. [DOI: 10.1016/j.brainresbull.2021.12.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/27/2021] [Accepted: 12/30/2021] [Indexed: 02/06/2023]
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25
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Sandhu A, Chopra T. Fecal microbiota transplantation for recurrent Clostridioides difficile, safety, and pitfalls. Therap Adv Gastroenterol 2021; 14:17562848211053105. [PMID: 34992678 PMCID: PMC8725027 DOI: 10.1177/17562848211053105] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 09/20/2021] [Indexed: 02/04/2023] Open
Abstract
Clostridioides difficile infection (CDI) is one of the leading causes of hospital-acquired infection attributing to substantial morbidity, mortality, and healthcare cost. Recurrent CDI (rCDI) is common and occurs after effective treatment of first episode. Treatment of rCDI is based on accurate diagnoses, due to difficulty in distinguishing between colonization of C. difficile spores or CDI; coronavirus disease 2019 (COVID-19) added to the complexity of diagnoses as both entities can co-occur. It is difficult to eradicate rCDI, and there remains a critical gap regarding treatment of rCDI. The treatment goal of rCDI is to reestablish normal microbiota. Fecal microbiota transplantation (FMT) is suggested as a treatment for second episode of rCDI. Based on the collective evidence of all randomized controlled trials, FMT was reported more efficacious compared with vancomycin or fidaxomicin; however, these trials had limited number of patients and all patients were pre-treated with vancomycin prior to FMT. Furthermore, when comparing various routes of instillation and types of preparation of fecal microbiota, no difference was observed in cure rate. Despite the success rate of FMT, there remains a concern for transmission of infectious agents, such as Gram negative bacteremia or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adverse events (diarrhea and abdominal pain), and reports of new diagnoses (inflammatory bowel disease, weight gain and irritable bowel syndrome). To lessen the risk of transmissible infections, donor screening should be performed, which includes screening for medical comorbidities and infectious pathogens in blood and feces. Scheduling complexities and reimbursement places an additional roadblock for using FMT. Microbiome-based therapies are being developed to eliminate the logistical challenges related to FMT. Large prospective and placebo-controlled studies are needed to evaluate the efficacy and long-term safety of FMT, so its use can be justified in clinical practice.
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Affiliation(s)
- Avnish Sandhu
- Department of Internal Medicine, Division of Infectious Disease, Wayne State Universit School of Medicine, Detroit Medical Center Detroit, MI, USA
| | - Teena Chopra
- Department of Internal Medicine, Division of Infectious Disease, Wayne State Universit School of Medicine, Detroit Medical Center Detroit, Harper University Hospital, 3990 John R street, Detroit, MI, 48201, USA
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26
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Pan B, Liu X, Shi J, Chen Y, Xu Z, Shi D, Ruan G, Wang F, Huang Y, Xu C. A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials. Front Nutr 2021; 8:775216. [PMID: 34977119 PMCID: PMC8714845 DOI: 10.3389/fnut.2021.775216] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/10/2021] [Indexed: 12/15/2022] Open
Abstract
Background and aims: Metabolic syndrome (MetS), accompanied with significant intestinal dysbiosis, causes a great public health burden to human society. Here, we carried out a meta-analysis to qualify randomized controlled trials (RCTs) and to systematically evaluate the effect of microbial therapy on MetS. Methods and results: Forty-two RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. Pooled estimates demonstrated that treatment with microbial therapy significantly reduced the waist circumference (WC) (SMD = -0.26, 95% CI -0.49, -0.03), fasting blood glucose (FBG) (SMD = -0.35, 95% CI -0.52, -0.18), total cholesterol (TC) (SMD = -0.36, 95% CI -0.55, -0.17), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.42, 95% CI -0.61, -0.22), and triacylglycerol (TG)(SMD = -0.38, 95% CI -0.55, -0.20), but increased the high-density lipoprotein cholesterol (HDL-C) (SMD = 0.28, 95% CI.03, 0.52). Sensitivity analysis indicated that after eliminating one study utilizing Bifidobacteriumlactis, results became statistically significant in diastolic blood pressure (DBP) (SMD = -0.24, 95% CI -0.41, -0.07) and in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD = -0.28, 95% CI -0.54, -0.03), while the body mass index (BMI) showed significant difference after eliminating one study utilizing oat bran (SMD = -0.16, 95% CI -0.31, -0.01). There was still no significant effect in systolic blood pressure (SBP) and in hemoglobin A1c (HbA1c%). Conclusion: In patients with MetS, the conditioning with microbial therapy notably improves FBG, TC, TG, HDL-C, LDL-C, WC, BMI (except for the study using oat bran), HOMA-IR, and DBP (except for the Study using Bifidobacteriumlactis), however, with no effect in SBP and in HbA1c%.
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Affiliation(s)
- Binhui Pan
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiujie Liu
- Institute of Ischemia/Reperfusion Injury, Wenzhou Medical University, Wenzhou, China
| | - Jiangmin Shi
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yaoxuan Chen
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhihua Xu
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Dibang Shi
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Gaoyi Ruan
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Fangyan Wang
- Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, China
| | - Yingpeng Huang
- Department of Gastrointestinal Oncology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Changlong Xu
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
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27
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Bernard R, Hourigan SK, Nicholson MR. Fecal Microbiota Transplantation and Microbial Therapeutics for the Treatment of Clostridioides difficile Infection in Pediatric Patients. J Pediatric Infect Dis Soc 2021; 10:S58-S63. [PMID: 34791396 PMCID: PMC8600035 DOI: 10.1093/jpids/piab056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and has high rates of recurrent disease. As a disease associated with intestinal dysbiosis, gastrointestinal microbiome manipulation and fecal microbiota transplantation (FMT) have evolved as effective, although relatively unregulated therapeutics and not without safety concerns. FMT for the treatment of CDI has been well studied in adults with increasing data reported in children. In this review, we discuss the current body of literature on the use of FMT in children including effectiveness, safety, risk factors for a failed FMT, and the role of FMT in children with comorbidities. We also review emerging microbial therapeutics for the treatment of rCDI.
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Affiliation(s)
- Rachel Bernard
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Monroe Carell Jr. Vanderbilt Children’s Hospital, Nashville, Tennessee, USA,Corresponding Author: Rachel Bernard, DO MS, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Monroe Carell Jr. Vanderbilt Children’s Hospital, 2200 Children’s Way, Suite 11226 Doctors’ Office Tower, Nashville, TN 38201, USA. E-mail:
| | - Suchitra K Hourigan
- Division of Pediatric Gastroenterology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA
| | - Maribeth R Nicholson
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Monroe Carell Jr. Vanderbilt Children’s Hospital, Nashville, Tennessee, USA
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28
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Abstract
Animals live in symbiosis with numerous microbe species. While some can protect hosts from infection and benefit host health, components of the microbiota or changes to the microbial landscape have the potential to facilitate infections and worsen disease severity. Pathogens and pathobionts can exploit microbiota metabolites, or can take advantage of a depletion in host defences and changing conditions within a host, to cause opportunistic infection. The microbiota might also favour a more virulent evolutionary trajectory for invading pathogens. In this review, we consider the ways in which a host microbiota contributes to infectious disease throughout the host's life and potentially across evolutionary time. We further discuss the implications of these negative outcomes for microbiota manipulation and engineering in disease management.
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Affiliation(s)
- Emily J. Stevens
- Department of Zoology, University of Oxford, Oxford, United Kingdom
| | - Kieran A. Bates
- Department of Zoology, University of Oxford, Oxford, United Kingdom
| | - Kayla C. King
- Department of Zoology, University of Oxford, Oxford, United Kingdom
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29
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Su F, Luo Y, Yu J, Shi J, Zhao Y, Yan M, Huang H, Tan Y. Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review. Eur J Med Res 2021; 26:37. [PMID: 33910622 PMCID: PMC8080403 DOI: 10.1186/s40001-021-00508-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 04/13/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Due to limited antibiotic options, carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Also, intestinal CRE colonization is a risk factor for subsequent CRE infection. Several clinical studies have reported successful fecal microbiota transplantation (FMT) for the gut decontamination of a variety of multidrug-resistant bacteria (MDRB), even in immunosuppressed patients. Similarly, other studies have also indicated that multiple FMTs may increase or lead to successful therapeutic outcomes. CASE PRESENTATION We report CRE colonization in an allo-HSCT patient with recurrent CRE infections, and its successful eradication using tandem FMT cycles at 488 days after allo-HSCT. We also performed a comprehensive microbiota analysis. No acute or delayed adverse events (AEs) were observed. The patient remained clinically stable with CRE-negative stool culture at 26-month follow-up. Our analyses also showed some gut microbiota reconstruction. We also reviewed the current literature on decolonization strategies for CRE. CONCLUSIONS CRE colonization led to a high no-relapse mortality after allo-HSCT; however, well-established decolonization strategies are currently lacking. The successful decolonization of this patient suggests that multiple FMT cycles may be potential options for CRE decolonization.
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Affiliation(s)
- Fengqin Su
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yi Luo
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Jian Yu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Jimin Shi
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yanmin Zhao
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Mengni Yan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yamin Tan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China. .,Hematology Department, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China.
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30
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Drug Response Diversity: A Hidden Bacterium? J Pers Med 2021; 11:jpm11050345. [PMID: 33922920 PMCID: PMC8146020 DOI: 10.3390/jpm11050345] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/12/2021] [Accepted: 04/22/2021] [Indexed: 11/27/2022] Open
Abstract
Interindividual heterogeneity in response to treatment is a real public health problem. It is a factor that can be responsible not only for ineffectiveness or fatal toxicity but also for hospitalization due to iatrogenic effects, thus increasing the cost of patient care. Several research teams have been interested in what may be at the origin of these phenomena, particularly at the genetic level and the basal activity of organs dedicated to the inactivation and elimination of drug molecules. Today, a new branch is being set up, explaining the enigmatic part that could not be explained before. Pharmacomicrobiomics attempts to investigate the interactions between bacteria, especially those in the gut, and drug response. In this review, we provide a state of the art on what this field has brought as new information and discuss the challenges that lie ahead to see the real application in clinical practice.
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31
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Mehta SR, Yen EF. Microbiota-based Therapies Clostridioides difficile infection that is refractory to antibiotic therapy. Transl Res 2021; 230:197-207. [PMID: 33278650 DOI: 10.1016/j.trsl.2020.11.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 11/05/2020] [Accepted: 11/29/2020] [Indexed: 11/27/2022]
Abstract
Clostridioides difficile infection (CDI) has had a devastating impact worldwide with significant rates of mortality, especially among the elderly. Despite effective antibiotics, the incidence of recurrent CDI (rCDI) is increasing and more difficult to treat with antibiotics alone. Fecal Microbiota Transplantation (FMT) has emerged as a consistently effective treatment for rCDI. Mechanisms for FMT are not entirely understood, but remain an area of active investigation. There have been recent safety reports with the use of FMT regarding transmission of pathogens in a few patients that have led to serious illness. With appropriate screening, FMT can be safely administered and continue to have a significant impact on eradication of rCDI and improve the lives of patients suffering from this disease. In this review, we summarize current treatments for CDI with a focus on microbiota-based therapies used for antibiotic refractory disease.
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Affiliation(s)
- Shama R Mehta
- NorthShore University HealthSystem, Division of Gastroenterology, 2650 Ridge Avenue, Suite G221, Evanston, IL 60201
| | - Eugene F Yen
- NorthShore University HealthSystem, Division of Gastroenterology, 2650 Ridge Avenue, Suite G221, Evanston, IL 60201.
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32
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van Son J, Koekkoek LL, La Fleur SE, Serlie MJ, Nieuwdorp M. The Role of the Gut Microbiota in the Gut-Brain Axis in Obesity: Mechanisms and Future Implications. Int J Mol Sci 2021; 22:ijms22062993. [PMID: 33804250 PMCID: PMC7999163 DOI: 10.3390/ijms22062993] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/12/2021] [Accepted: 03/13/2021] [Indexed: 12/17/2022] Open
Abstract
Interaction between the gut and the brain is essential for energy homeostasis. In obesity, this homeostasis is disrupted, leading to a positive energy balance and weight gain. Obesity is a global epidemic that affects individual health and strains the socioeconomic system. Microbial dysbiosis has long been reported in obesity and obesity-related disorders. More recent literature has focused on the interaction of the gut microbiota and its metabolites on human brain and behavior. Developing strategies that target the gut microbiota could be a future approach for the treatment of obesity. Here, we review the microbiota–gut–brain axis and possible therapeutic options.
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Affiliation(s)
- Jamie van Son
- Department of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.v.S.); (L.L.K.); (S.E.L.F.); (M.J.S.)
- Department of Vascular Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Laura L. Koekkoek
- Department of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.v.S.); (L.L.K.); (S.E.L.F.); (M.J.S.)
| | - Susanne E. La Fleur
- Department of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.v.S.); (L.L.K.); (S.E.L.F.); (M.J.S.)
| | - Mireille J. Serlie
- Department of Endocrinology and Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.v.S.); (L.L.K.); (S.E.L.F.); (M.J.S.)
| | - Max Nieuwdorp
- Department of Vascular Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Correspondence:
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Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 2021; 40:1383-1392. [PMID: 33496893 DOI: 10.1007/s10096-021-04163-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 01/11/2021] [Indexed: 01/20/2023]
Abstract
Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3 months (range 2-7.7 months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.
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García-Cabrerizo R, Carbia C, O Riordan KJ, Schellekens H, Cryan JF. Microbiota-gut-brain axis as a regulator of reward processes. J Neurochem 2021; 157:1495-1524. [PMID: 33368280 DOI: 10.1111/jnc.15284] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 12/08/2020] [Accepted: 12/21/2020] [Indexed: 12/14/2022]
Abstract
Our gut harbours trillions of microorganisms essential for the maintenance of homeostasis and host physiology in health and disease. In the last decade, there has been a growing interest in understanding the bidirectional pathway of communication between our microbiota and the central nervous system. With regard to reward processes there is accumulating evidence from both animal and human studies that this axis may be a key factor in gating reward valence. Focusing on the mesocorticolimbic pathway, we will discuss how the intestinal microbiota is involved in regulating brain reward functions, both in natural (i.e. eating, social or sexual behaviours) and non-natural reinforcers (drug addiction behaviours including those relevant to alcohol, psychostimulants, opioids and cannabinoids). We will integrate preclinical and clinical evidence suggesting that the microbiota-gut-brain axis could be implicated in the development of disorders associated with alterations in the reward system and how it may be targeted as a promising therapeutic strategy. Cover Image for this issue: https://doi.org/10.1111/jnc.15065.
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Affiliation(s)
| | - Carina Carbia
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | | | - Harriet Schellekens
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
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Hammeken LH, Baunwall SMD, Hvas CL, Ehlers LH. Health economic evaluations comparing faecal microbiota transplantation with antibiotics for treatment of recurrent Clostridioides difficile infection: a systematic review. HEALTH ECONOMICS REVIEW 2021; 11:3. [PMID: 33439367 PMCID: PMC7805077 DOI: 10.1186/s13561-021-00301-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 01/04/2021] [Indexed: 05/10/2023]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is increasingly being used in the treatment of recurrent Clostridioides difficile infection (rCDI). Health economic evaluations may support decision-making regarding the implementation of FMT in clinical practice. Previous reviews have highlighted several methodological concerns in published health economic evaluations examining FMT. However, the impact of these concerns on the conclusions of the studies remains unclear. AIMS To present an overview and assess the methodological quality of health economic evaluations that compare FMT with antibiotics for treatment of rCDI. Furthermore, we aimed to evaluate the degree to which any methodological concerns would affect conclusions about the cost-effectiveness of FMT. METHODS We conducted a systematic literature review based on a search in seven medical databases up to 16 July 2020. We included research articles reporting on full health economic evaluations comparing FMT with antibiotic treatment for rCDI. General study characteristics and input estimates for costs, effectiveness and utilities were extracted from the articles. The quality of the studies was assessed by two authors using the Drummonds ten-point checklist. RESULTS We identified seven cost-utility analyses. All studies applied decision-analytic modelling and compared various FMT delivery methods with vancomycin, fidaxomicin, metronidazole or a combination of vancomycin and bezlotoxumab. The time horizons used in the analyses varied from 78 days to lifelong, and the perspectives differed between a societal, a healthcare system or a third-party payer perspective. The applied willingness-to-pay threshold ranged from 20,000 to 68,000 Great Britain pound sterling (GBP) per quality-adjusted life-year (QALY). FMT was considered the most cost-effective alternative in all studies. In five of the health economic evaluations, FMT was both more effective and cost saving than antibiotic treatment alternatives. The quality of the articles varied, and we identified several methodological concerns. CONCLUSIONS Economic evaluations consistently reported that FMT is a cost-effective and potentially cost-saving treatment for rCDI. Based on a comparison with recent evidence within the area, the multiple methodological concerns seem not to change this conclusion. Therefore, implementing FMT for rCDI in clinical practice should be strongly considered.
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Affiliation(s)
- Lianna Hede Hammeken
- Danish Center for Healthcare Improvements, Department of Clinical Medicine, Aalborg University, Fredrik Bajers Vej 5, DK-9220 Aalborg Ø, Denmark
| | - Simon Mark Dahl Baunwall
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark
| | - Lars Holger Ehlers
- Danish Center for Healthcare Improvements, Department of Clinical Medicine, Aalborg University, Fredrik Bajers Vej 5, DK-9220 Aalborg Ø, Denmark
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Singh A, Mahajan R, Kao D, Midha V, Sood A. Long term management of ulcerative colitis with Faecal Microbiota Transplantation. MEDICINE IN MICROECOLOGY 2020. [DOI: 10.1016/j.medmic.2020.100026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Luo Y, Tixier EN, Grinspan AM. Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults Is Associated with Early Recurrence. Dig Dis Sci 2020; 65:3647-3651. [PMID: 32078714 DOI: 10.1007/s10620-020-06147-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 02/11/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI). CDI disproportionately affects the elderly; however, there is a paucity of data on FMT effectiveness in older adults, especially subpopulations at highest risk for CDI-related morbidity and mortality. AIM To assess the efficacy and safety of FMT for CDI in older adults. METHODS A retrospective, long-term follow-up study was performed. The high-risk subpopulation included patients who were immunocompromised, patients with inflammatory bowel disease, and patients presenting with severe or fulminant colitis. Outcome measures included primary cure rates, early (< 12 weeks) and late (> 12 weeks) recurrence rates, adverse events, and subgroup analysis of higher-risk populations. RESULTS Our cohort included 75 patients (72% female) with a mean age of 76.4 and Charlson comorbidity index score of 5.4. There were 34 patients in our higher-risk subpopulation as defined above with an adjusted recurrence rate of 32.1%. FMT was performed for severe or fulminant disease in 30.6% of patients with a 3-month survival rate of 73.9%. Overall, the adjusted primary cure rate was 67.2% and the adjusted CDI recurrence was 29.9% in our cohort (90% of recurrences occurred early). Most adverse events in our study were rehospitalizations for recurrent CDI. CONCLUSION Compared with previous studies of FMT efficacy, our cohort had a lower primary cure rate and higher CDI recurrence rate than previously reported, likely driven by our higher-risk subpopulations. Nevertheless, FMT should be considered early to prevent progression of CDI severity and recurrence, especially in patients who present with severe and fulminant disease.
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Affiliation(s)
- Yuying Luo
- Department of Medicine, The Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA.
| | - Emily N Tixier
- The Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, 10029, USA
| | - Ari M Grinspan
- The Henry D. Janowitz Division of Gastroenterology, The Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, 10029, USA
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Merli P, Putignani L, Ruggeri A, Del Chierico F, Gargiullo L, Galaverna F, Gaspari S, Pagliara D, Russo A, Pane S, Strocchio L, Algeri M, Rea F, Francesca Romeo E, Bernaschi P, Onetti Muda A, Dallapiccola B, Locatelli F. Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes. Haematologica 2020; 105:2686-2690. [PMID: 33131263 PMCID: PMC7604639 DOI: 10.3324/haematol.2019.244210] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Pietro Merli
- Hematology/Oncology, Cellular and Gene Therapy, Bambino Gesù Children's Hospital, Rome, Italy
| | - Lorenza Putignani
- Unit of Parasitology and of Human Microbiome, Bambino Gesù Children's Hospital, Rome, Italy
| | - Annalisa Ruggeri
- Hematology/Oncology, Cellular and Gene Therapy, Bambino Gesù Children's Hospital, Rome, Italy
| | | | - Livia Gargiullo
- Unit of Immunology and Infectious Diseases, Bambino Gesù Children's Hospital, Rome, Italy
| | - Federica Galaverna
- Hematology/Oncology, Cellular and Gene Therapy, Bambino Gesù Children's Hospital, Rome, Italy
| | - Stefania Gaspari
- Hematology/Oncology, Cellular and Gene Therapy, Bambino Gesù Children's Hospital, Rome, Italy
| | - Daria Pagliara
- Hematology/Oncology, Cellular and Gene Therapy, Bambino Gesù Children's Hospital, Rome, Italy
| | - Alessandra Russo
- Unit of Human Microbiome, Bambino Gesù Children's Hospital, Rome, Italy
| | - Stefania Pane
- Unit of Parasitology, Bambino Gesù Children's Hospital, Rome, Italy
| | - Luisa Strocchio
- Hematology/Oncology, Cellular and Gene Therapy, Bambino Gesù Children's Hospital, Rome, Italy
| | - Mattia Algeri
- Hematology/Oncology, Cellular and Gene Therapy, Bambino Gesù Children's Hospital, Rome, Italy
| | - Francesca Rea
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital, Rome, Italy
| | | | - Paola Bernaschi
- Unit of Microbiology, Bambino Gesù Children's Hospital, Rome, Italy
| | - Andrea Onetti Muda
- Department of Laboratories, Bambino Gesù Children's Hospital, Rome, Italy
| | | | - Franco Locatelli
- Dept. of Hematology/Oncology, Cellular and Gene Therapy,Bambino Gesù Children Hospital,Rome
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Shang Z, Chan SY, Song Q, Li P, Huang W. The Strategies of Pathogen-Oriented Therapy on Circumventing Antimicrobial Resistance. RESEARCH (WASHINGTON, D.C.) 2020; 2020:2016201. [PMID: 33083786 PMCID: PMC7539235 DOI: 10.34133/2020/2016201] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/02/2020] [Indexed: 12/23/2022]
Abstract
The emerging antimicrobial resistance (AMR) poses serious threats to the global public health. Conventional antibiotics have been eclipsed in combating with drug-resistant bacteria. Moreover, the developing and deploying of novel antimicrobial drugs have trudged, as few new antibiotics are being developed over time and even fewer of them can hit the market. Alternative therapeutic strategies to resolve the AMR crisis are urgently required. Pathogen-oriented therapy (POT) springs up as a promising approach in circumventing antibiotic resistance. The tactic underling POT is applying antibacterial compounds or materials directly to infected regions to treat specific bacteria species or strains with goals of improving the drug efficacy and reducing nontargeting and the development of drug resistance. This review exemplifies recent trends in the development of POTs for circumventing AMR, including the adoption of antibiotic-antibiotic conjugates, antimicrobial peptides, therapeutic monoclonal antibodies, nanotechnologies, CRISPR-Cas systems, and microbiota modulations. Employing these alternative approaches alone or in combination shows promising advantages for addressing the growing clinical embarrassment of antibiotics in fighting drug-resistant bacteria.
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Affiliation(s)
- Zifang Shang
- Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Northwestern Polytechnical University (NPU), Xi'an 710072, China
| | - Siew Yin Chan
- Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Northwestern Polytechnical University (NPU), Xi'an 710072, China
| | - Qing Song
- Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Northwestern Polytechnical University (NPU), Xi'an 710072, China
- Key Laboratory for Organic Electronics and Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications (NUPT), Nanjing 210023, China
| | - Peng Li
- Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Northwestern Polytechnical University (NPU), Xi'an 710072, China
| | - Wei Huang
- Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Northwestern Polytechnical University (NPU), Xi'an 710072, China
- Key Laboratory for Organic Electronics and Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications (NUPT), Nanjing 210023, China
- Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China
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Shabat Y, Lichtenstein Y, Ilan Y. Short-Term Cohousing of Sick with Healthy or Treated Mice Alleviates the Inflammatory Response and Liver Damage. Inflammation 2020; 44:518-525. [PMID: 32978699 DOI: 10.1007/s10753-020-01348-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 08/19/2020] [Accepted: 09/22/2020] [Indexed: 01/08/2023]
Abstract
Cohousing of sick with healthy or treated animals is based on the concept of sharing an intestinal ecosystem and coprophagy, the consumption of feces, which includes sharing of the microbiome and of active drug metabolites secreted in the feces or urine. To develop a model for short-term cohousing, enabling the study of the effect of sharing an ecosystem on inflammatory states. To determine the impact of cohousing of sick and healthy mice on the immune-mediated disorders, mice injected with concanavalin A (ConA) were cohoused with healthy or sick mice or with steroid-treated or untreated mice. To determine the effect of cohousing on acetaminophen (APAP)-induced liver damage, APAP-injected mice were cohoused with N-acetyl-cysteine (NAC)-treated or untreated mice. In the ConA-induced immune-mediated hepatitis model, cohousing of sick with healthy mice was associated with the alleviation of liver damage in sick animals. Similarly, a significant decrease in serum ALT was noted in ConA-injected mice kept in the same cage as ConA-injected mice treated with steroids. A trend for reduction in liver enzymes in APAP-injected mice was observed upon cohousing with NAC-treated animals. Cohousing of sick mice with healthy or treated mice ameliorated the immune-mediated inflammatory state induced by ConA and APAP. These models for liver damage can serve as biological systems for determining the effects of alterations in the ecosystem on the immune system.
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Affiliation(s)
- Yehudit Shabat
- Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Ein-Kerem, POB 1200, IL91120, Jerusalem, Israel
| | - Yoav Lichtenstein
- Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Ein-Kerem, POB 1200, IL91120, Jerusalem, Israel
| | - Yaron Ilan
- Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Ein-Kerem, POB 1200, IL91120, Jerusalem, Israel.
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Feng W, Liu J, Ao H, Yue S, Peng C. Targeting gut microbiota for precision medicine: Focusing on the efficacy and toxicity of drugs. Theranostics 2020; 10:11278-11301. [PMID: 33042283 PMCID: PMC7532689 DOI: 10.7150/thno.47289] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 08/20/2020] [Indexed: 02/06/2023] Open
Abstract
Intra- and interindividual variation in drug responses is one major reason for the failure of drug therapy, drug toxicity, and even the death of patients. Precision medicine, or personalized medicine, is a field of medicine that customizes an individual's medical diagnosis and treatment based on his/her genes, microbiomes, environments, etc. Over the past decade, a large number of studies have demonstrated that gut microbiota can modify the efficacy and toxicity of drugs, and the extent of the modification varies greatly from person to person because of the variability of the gut microbiota. Personalized manipulation of gut microbiota is an important approach to rectify the abnormal drug response. In this review, we aim to improve drug efficacy and reduce drug toxicity by combining precision medicine and gut microbiota. After describing the interactions between gut microbiota and xenobiotics, we discuss (1) the effects of gut microbiota on drug efficacy and toxicity and the corresponding mechanisms, (2) the variability of gut microbiota, which leads to variation in drug responses, (3) the biomarkers used for the patient stratification and treatment decisions before the use of drugs, and (4) the methods used for the personalized manipulation of gut microbiota to improve drug outcomes. Overall, we hope to improve the drug response by incorporating the knowledge of gut microbiota into clinical practice.
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Affiliation(s)
- Wuwen Feng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Juan Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hui Ao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shijun Yue
- Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Cheng Peng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Gulati M, Singh SK, Corrie L, Kaur IP, Chandwani L. Delivery routes for faecal microbiota transplants: Available, anticipated and aspired. Pharmacol Res 2020; 159:104954. [DOI: 10.1016/j.phrs.2020.104954] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/11/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023]
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Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis. Mediators Inflamm 2020; 2020:2058272. [PMID: 32831634 PMCID: PMC7426773 DOI: 10.1155/2020/2058272] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 06/18/2020] [Accepted: 07/13/2020] [Indexed: 12/20/2022] Open
Abstract
Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.
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Mateu L, Fernández-Rivas G, Sopena N. Diagnosis and treatment of Clostridioides difficile infection. Med Clin (Barc) 2020; 155:30-35. [PMID: 32430207 DOI: 10.1016/j.medcli.2020.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 02/21/2020] [Accepted: 02/24/2020] [Indexed: 02/08/2023]
Abstract
Clostridioides difficile is the main cause of healthcare-associated diarrhoea in adults. The incidence of C.difficile infection (CDI) has increased in recent years. The risk of recurrence of CDI is 15%-25% in a first episode and this risk is increased in subsequent episodes. Toxigenic culture and cytotoxicity tests are the reference techniques for the microbiological diagnosis of CDI. These are laborious and slow techniques and therefore they have been replaced in clinical practice by the application of a multi-step algorithm that includes the detection of glutamate dehydrogenase (GDH), toxins and molecular techniques. The treatment of choice for CDI is Vancomycin. In recent years, new drugs and new treatment strategies have appeared that are especially useful in the treatment of relapses of CDI.
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Affiliation(s)
- Lourdes Mateu
- Servicio de Enfermedades Infecciosas, Hospital Universitari Germans Trias i Pujol. Departamento de Medicina, Universitat Autònoma de Barcelona. Institut de Recerca Germans Trias i Pujol. CIBER de Enfermedades Respiratorias, Badalona, Barcelona, España.
| | - Gema Fernández-Rivas
- Servicio de Microbiología, Laboratorio Clínico de la Metropolitana Norte, Hospital Universitari Germans Trias i Pujol. Departamento de Genética y Microbiología, Universitat Autònoma de Barcelona. Institut de Recerca Germans Trias i Pujol, Badalona, Barcelona, España
| | - Nieves Sopena
- Servicio de Enfermedades Infecciosas, Hospital Universitari Germans Trias i Pujol. Departamento de Medicina, Universitat Autònoma de Barcelona. Institut de Recerca Germans Trias i Pujol. CIBER de Enfermedades Respiratorias, Badalona, Barcelona, España
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Haifer C, Kelly CR, Paramsothy S, Andresen D, Papanicolas LE, McKew GL, Borody TJ, Kamm M, Costello SP, Andrews JM, Begun J, Chan HT, Connor S, Ghaly S, Johnson PD, Lemberg DA, Paramsothy R, Redmond A, Sheorey H, van der Poorten D, Leong RW. Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice. Gut 2020; 69:801-810. [PMID: 32047093 DOI: 10.1136/gutjnl-2019-320260] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 12/17/2019] [Accepted: 12/27/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications. DESIGN For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RESULTS Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development. CONCLUSIONS These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.
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Affiliation(s)
- Craig Haifer
- The University of Sydney, Sydney, New South Wales, Australia
- St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Colleen R Kelly
- Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA
| | - Sudarshan Paramsothy
- The University of Sydney, Sydney, New South Wales, Australia
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - David Andresen
- The University of Sydney, Sydney, New South Wales, Australia
- St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Lito E Papanicolas
- South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
- Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Genevieve L McKew
- The University of Sydney, Sydney, New South Wales, Australia
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Thomas J Borody
- Centre for Digestive Diseases, Sydney, New South Wales, Australia
| | - Michael Kamm
- St Vincent's Hospital, Melbourne, Victoria, Australia
- The University of Melbourne, Melbourne, Victoria, Australia
| | - Samuel P Costello
- The Queen Elizabeth Hospital, Woodville, South Australia, Australia
- BiomeBank, Adelaide, South Australia, Australia
| | - Jane M Andrews
- Royal Adelaide Hospital, Adelaide, South Australia, Australia
- The University of Adelaide, Adelaide, South Australia, Australia
| | - Jakob Begun
- The University of Queensland, Brisbane, Queensland, Australia
- Mater Hospital Brisbane, Brisbane, Queensland, Australia
| | | | - Susan Connor
- Liverpool Hospital, Sydney, New South Wales, Australia
- University of New South Wales, Sydney, New South Wales, Australia
| | - Simon Ghaly
- St Vincent's Hospital, Sydney, New South Wales, Australia
- University of New South Wales, Sydney, New South Wales, Australia
| | - Paul Dr Johnson
- The University of Melbourne, Melbourne, Victoria, Australia
- Austin Hospital, Melbourne, Victoria, Australia
| | - Daniel A Lemberg
- University of New South Wales, Sydney, New South Wales, Australia
- Sydney Children's Hospital Randwick, Randwick, New South Wales, Australia
| | | | - Andrew Redmond
- The University of Queensland, Brisbane, Queensland, Australia
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | | | - David van der Poorten
- The University of Sydney, Sydney, New South Wales, Australia
- Westmead Hospital, Sydney, New South Wales, Australia
| | - Rupert W Leong
- The University of Sydney, Sydney, New South Wales, Australia
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
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Fond GB, Lagier JC, Honore S, Lancon C, Korchia T, Verville PLSD, Llorca PM, Auquier P, Guedj E, Boyer L. Microbiota-Orientated Treatments for Major Depression and Schizophrenia. Nutrients 2020; 12:nu12041024. [PMID: 32276499 PMCID: PMC7230529 DOI: 10.3390/nu12041024] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 03/31/2020] [Accepted: 04/02/2020] [Indexed: 12/13/2022] Open
Abstract
Background and significance. There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. Method. This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. Results. The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics’ impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. Conclusion. Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.
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Affiliation(s)
- Guillaume B. Fond
- Hôpitaux Universitaires de Marseille, Department de Psychiatrie universitaire, EA 3279: Aix-Marseille Université, CEReSS—Health Service Research and Quality of Life Center, 27 Boulevard Jean Moulin, 13005 Marseille, France; (S.H.); (C.L.); (T.K.); (P.-L.S.D.V.); (P.A.); (L.B.)
- Correspondence:
| | - Jean-Christophe Lagier
- Aix Marseille University, Institut de Recherche pour le Développement, Microbes Evolution Phylogeny and Infection, Assistance Publique Hôpitaux de Marseille, Institut Hospitalo Universitaire Méditerranée Infection, 13005 Marseille, France;
| | - Stéphane Honore
- Hôpitaux Universitaires de Marseille, Department de Psychiatrie universitaire, EA 3279: Aix-Marseille Université, CEReSS—Health Service Research and Quality of Life Center, 27 Boulevard Jean Moulin, 13005 Marseille, France; (S.H.); (C.L.); (T.K.); (P.-L.S.D.V.); (P.A.); (L.B.)
| | - Christophe Lancon
- Hôpitaux Universitaires de Marseille, Department de Psychiatrie universitaire, EA 3279: Aix-Marseille Université, CEReSS—Health Service Research and Quality of Life Center, 27 Boulevard Jean Moulin, 13005 Marseille, France; (S.H.); (C.L.); (T.K.); (P.-L.S.D.V.); (P.A.); (L.B.)
| | - Théo Korchia
- Hôpitaux Universitaires de Marseille, Department de Psychiatrie universitaire, EA 3279: Aix-Marseille Université, CEReSS—Health Service Research and Quality of Life Center, 27 Boulevard Jean Moulin, 13005 Marseille, France; (S.H.); (C.L.); (T.K.); (P.-L.S.D.V.); (P.A.); (L.B.)
| | - Pierre-Louis Sunhary De Verville
- Hôpitaux Universitaires de Marseille, Department de Psychiatrie universitaire, EA 3279: Aix-Marseille Université, CEReSS—Health Service Research and Quality of Life Center, 27 Boulevard Jean Moulin, 13005 Marseille, France; (S.H.); (C.L.); (T.K.); (P.-L.S.D.V.); (P.A.); (L.B.)
| | | | - Pascal Auquier
- Hôpitaux Universitaires de Marseille, Department de Psychiatrie universitaire, EA 3279: Aix-Marseille Université, CEReSS—Health Service Research and Quality of Life Center, 27 Boulevard Jean Moulin, 13005 Marseille, France; (S.H.); (C.L.); (T.K.); (P.-L.S.D.V.); (P.A.); (L.B.)
| | - Eric Guedj
- Aix-Marseille Université, CNRS, Ecole Centrale de Marseille, UMR 7249, Institut Fresnel, Département de médecine nucléaire, CERIMED, Aix-Marseille Université, F-13005 Marseille, France;
| | - Laurent Boyer
- Hôpitaux Universitaires de Marseille, Department de Psychiatrie universitaire, EA 3279: Aix-Marseille Université, CEReSS—Health Service Research and Quality of Life Center, 27 Boulevard Jean Moulin, 13005 Marseille, France; (S.H.); (C.L.); (T.K.); (P.-L.S.D.V.); (P.A.); (L.B.)
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Spinner JA, Bocchini CE, Luna RA, Thapa S, Balderas MA, Denfield SW, Dreyer WJ, Nagy-Szakal D, Ihekweazu FD, Versalovic J, Savidge T, Kellermayer R. Fecal microbiota transplantation in a toddler after heart transplant was a safe and effective treatment for recurrent Clostridiodes difficile infection: A case report. Pediatr Transplant 2020; 24:e13598. [PMID: 31617299 PMCID: PMC6982574 DOI: 10.1111/petr.13598] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 08/19/2019] [Accepted: 09/01/2019] [Indexed: 12/17/2022]
Abstract
Pediatric recipients of SOT have a significantly increased risk of Clostridiodes (formerly Clostridium) difficile infection (CDI), which is associated with adverse outcomes after SOT. Alterations to the intestinal microbiota community structure increase the risk of CDI. FMT is a safe and effective treatment for recurrent CDI in immunocompetent children and adults. While there are increasing data that FMT in immunosuppressed patients is safe and effective without increased risk of infection, data regarding safety and efficacy of FMT in children after SOT are limited. To our knowledge, we report the youngest immunocompromised patient to undergo FMT and the third overall case of FMT in a child after HTx. Our patient presented with five episodes of rCDI in 6 months, and 16S rRNA genetic analysis revealed significant loss of overall microbiota community structure and diversity prior to FMT compared with a donor and a healthy, age-matched control. After FMT, marked and prolonged (at least 16 months) shifts in the recipient microbiota community structure and diversity were evident, approaching that of donor and healthy, age-matched control. FMT was well tolerated, restored microbial diversity without any graft or transplant complications, and prevented further rCDI episodes after more than 4 years of follow-up.
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Affiliation(s)
- Joseph A Spinner
- Section of Pediatric Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX
| | - Claire E Bocchini
- Section of Pediatric Infectious Disease, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX
| | - Ruth A Luna
- Texas Children’s Microbiome Center and Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX
| | - Santosh Thapa
- Texas Children’s Microbiome Center and Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX
| | - Miriam A Balderas
- Texas Children’s Microbiome Center and Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX
| | - Susan W Denfield
- Section of Pediatric Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX
| | - William J Dreyer
- Section of Pediatric Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX
| | - Dorottya Nagy-Szakal
- Section of Pediatric Gastroenterology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX,USDA/ARS Children’s Nutrition Research Center, Houston, TX, USA
| | - Faith D Ihekweazu
- Section of Pediatric Gastroenterology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX
| | - James Versalovic
- Texas Children’s Microbiome Center and Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX
| | - Tor Savidge
- Texas Children’s Microbiome Center and Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX
| | - Richard Kellermayer
- Section of Pediatric Gastroenterology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX,USDA/ARS Children’s Nutrition Research Center, Houston, TX, USA
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Treatment of Severe and Fulminnant Clostridioides difficile Infection. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2019; 17:524-533. [PMID: 31745820 DOI: 10.1007/s11938-019-00262-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW This article will review current management strategies for severe and fulminant Clostridioides difficile infection (CDI). RECENT FINDINGS Clostridioides difficile is the most common nosocomial cause of infectious diarrhea. With the rise of hypervirulent strains of CDI, almost 8% of patients hospitalized with CDI are afflicted with severe CDI (SCDI) or fulminant CDI (FCDI). A significant proportion of these patients do not respond to recommended anti-CDI antibiotic therapy such as oral vancomycin and fidaxomicin. Current recommendations suggest that patients with refractory CDI should proceed to colectomy or diverting loop ileostomy with colonic lavage. However, both of these surgical interventions result in high rates of post-surgical mortality approaching 30%. Fecal microbiota transplantation (FMT) is a promising therapy that is recommended in recurrent CDI. Recent studies have found that FMT can safely produce cure rates between 70 and 90% in patients with SCDI and FCDI, while significantly decreasing rates of CDI-related mortality and colectomy. A patient population likely to benefit the most from FMT is elderly patients due to their increased risk for CDI, treatment failure, and high comorbidity burden that may preclude surgical intervention. FMT should be considered in patients with SCDI or FCDI particularly when traditional anti-CDI antibiotics are ineffective.
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Yoon YK, Suh JW, Kang EJ, Kim JY. Efficacy and safety of fecal microbiota transplantation for decolonization of intestinal multidrug-resistant microorganism carriage: beyond Clostridioides difficile infection. Ann Med 2019; 51:379-389. [PMID: 31468999 PMCID: PMC7877873 DOI: 10.1080/07853890.2019.1662477] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Persistent reservoirs of multidrug-resistant microorganisms (MDRO) that are prevalent in hospital settings and communities can lead to the spread of MDRO. Currently, there are no effective decolonization strategies, especially non-pharmacological strategies without antibiotic regimens. Our aim was to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the eradication of MDRO. A systematic literature search was performed to identify studies on the use of FMT for the decolonization of MDRO. PubMed, EMBASE, Web of Science, and Cochrane Library were searched from inception through January 2019. Of the 1395 articles identified, 20 studies met the inclusion and exclusion criteria. Overall, the efficacy of FMT for the eradication of each MDRO was 70.3% (102/146) in 121 patients from the 20 articles. The efficacy rates were 68.2% (30/44) for gram-positive bacteria and 70.6% (72/102) for gram-negative bacteria. Minor adverse events, including vomiting, diarrhea, abdominal pain, and ileus, were reported in patients who received FMT. FMT could be a promising strategy to eradicate MDRO in patients. Further studies are needed to confirm these findings and establish a comprehensive FMT protocol for standardized treatment.Key messagesThe development of new antibiotics lags behind the emergence of multidrug-resistant microorganisms (MDRO). New strategies are needed.Theoretically, fecal microbiota transplantation (FMT) might recover the diversity and function of commensal microbiota from dysbiosis in MDRO carriers and help restore colonization resistance to pathogens.A literature review indicated that FMT could be a promising strategy to eradicate MDRO in patients.
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Affiliation(s)
- Young Kyung Yoon
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jin Woong Suh
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Eun-Ji Kang
- Korea University Medical Library, Seoul, Korea
| | - Jeong Yeon Kim
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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50
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Drewes JL, Corona A, Sanchez U, Fan Y, Hourigan SK, Weidner M, Sidhu SD, Simner PJ, Wang H, Timp W, Oliva-Hemker M, Sears CL. Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile. JCI Insight 2019; 4:130848. [PMID: 31578306 DOI: 10.1172/jci.insight.130848] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 09/04/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUNDFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) in adults and children, but donor stool samples are currently screened for only a limited number of potential pathogens. We sought to determine whether putative procarcinogenic bacteria (enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT.METHODSStool samples were collected from 11 pediatric rCDI patients and their respective FMT donors prior to FMT as well as from the patients at 2-10 weeks, 10-20 weeks, and 6 months after FMT. Bacterial virulence factors in stool DNA extracts and stool cultures were measured by quantitative PCR: Bacteroides fragilis toxin (bft), Fusobacterium adhesin A (fadA), and Escherichia coli colibactin (clbB).RESULTSFour of 11 patients demonstrated sustained acquisition of a procarcinogenic bacteria. Whole genome sequencing was performed on colony isolates from one of these donor/recipient pairs and demonstrated that clbB+ E. coli strains present in the recipient after FMT were identical to a strain present in the donor, confirming strain transmission. Conversely, 2 patients exhibited clearance of procarcinogenic bacteria following FMT from a negative donor.CONCLUSIONBoth durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted.FUNDINGCrohn's & Colitis Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, the National Cancer Institute, and the Canadian Institutes of Health Research.
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Affiliation(s)
- Julia L Drewes
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Alina Corona
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Uriel Sanchez
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Yunfan Fan
- Department of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, Maryland, USA
| | - Suchitra K Hourigan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Melissa Weidner
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sarah D Sidhu
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Hao Wang
- Department of Oncology, Bioinformatics and Biostatistics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Winston Timp
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,Department of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, Maryland, USA
| | - Maria Oliva-Hemker
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Cynthia L Sears
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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