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Porcari S, Fusco W, Spivak I, Fiorani M, Gasbarrini A, Elinav E, Cammarota G, Ianiro G. Fine-tuning the gut ecosystem: the current landscape and outlook of artificial microbiome therapeutics. Lancet Gastroenterol Hepatol 2024; 9:460-475. [PMID: 38604200 DOI: 10.1016/s2468-1253(23)00357-6] [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] [Received: 07/18/2023] [Revised: 10/04/2023] [Accepted: 10/10/2023] [Indexed: 04/13/2024]
Abstract
The gut microbiome is acknowledged as a key determinant of human health, and technological progress in the past two decades has enabled the deciphering of its composition and functions and its role in human disorders. Therefore, manipulation of the gut microbiome has emerged as a promising therapeutic option for communicable and non-communicable disorders. Full exploitation of current therapeutic microbiome modulators (including probiotics, prebiotics, and faecal microbiota transplantation) is hindered by several factors, including poor precision, regulatory and safety issues, and the impossibility of providing reproducible and targeted treatments. Artificial microbiota therapeutics (which include a wide range of products, such as microbiota consortia, bacteriophages, bacterial metabolites, and engineered probiotics) have appeared as an evolution of current microbiota modulators, as they promise safe and reproducible effects, with variable levels of precision via different pathways. We describe the landscape of artificial microbiome therapeutics, from those already on the market to those still in the pipeline, and outline the major challenges for positioning these therapeutics in clinical practice.
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Affiliation(s)
- Serena Porcari
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - William Fusco
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Igor Spivak
- Systems Immunology Department, Weizmann Institute of Science, Rehovot, Israel; Medical Clinic III, University Hospital Aachen, Aachen, Germany
| | - Marcello Fiorani
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Eran Elinav
- Systems Immunology Department, Weizmann Institute of Science, Rehovot, Israel; Microbiome and Cancer Division, DKFZ, Heidelberg, Germany
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; UOC Gastroenterologia and UOC CEMAD Medicina Interna e Gastroenterologia, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
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Belei O, Basaca DG, Olariu L, Pantea M, Bozgan D, Nanu A, Sîrbu I, Mărginean O, Enătescu I. The Interaction between Stress and Inflammatory Bowel Disease in Pediatric and Adult Patients. J Clin Med 2024; 13:1361. [PMID: 38592680 PMCID: PMC10932475 DOI: 10.3390/jcm13051361] [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: 01/27/2024] [Revised: 02/23/2024] [Accepted: 02/25/2024] [Indexed: 04/10/2024] Open
Abstract
Background: Inflammatory bowel diseases (IBDs) have seen an exponential increase in incidence, particularly among pediatric patients. Psychological stress is a significant risk factor influencing the disease course. This review assesses the interaction between stress and disease progression, focusing on articles that quantified inflammatory markers in IBD patients exposed to varying degrees of psychological stress. Methods: A systematic narrative literature review was conducted, focusing on the interaction between IBD and stress among adult and pediatric patients, as well as animal subjects. The research involved searching PubMed, Scopus, Medline, and Cochrane Library databases from 2000 to December 2023. Results: The interplay between the intestinal immunity response, the nervous system, and psychological disorders, known as the gut-brain axis, plays a major role in IBD pathophysiology. Various types of stressors alter gut mucosal integrity through different pathways, increasing gut mucosa permeability and promoting bacterial translocation. A denser microbial load in the gut wall emphasizes cytokine production, worsening the disease course. The risk of developing depression and anxiety is higher in IBD patients compared with the general population, and stress is a significant trigger for inducing acute flares of the disease. Conclusions: Further large studies should be conducted to assess the relationship between stressors, psychological disorders, and their impact on the course of IBD. Clinicians involved in the medical care of IBD patients should aim to implement stress reduction practices in addition to pharmacological therapies.
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Affiliation(s)
- Oana Belei
- First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (O.B.); (O.M.)
- Department of Pediatrics, First Pediatric Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Diana-Georgiana Basaca
- First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (O.B.); (O.M.)
- Department of Pediatrics, First Pediatric Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Laura Olariu
- Department of Pediatrics, First Pediatric Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Manuela Pantea
- Twelfth Department, Neonatology Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (M.P.); (I.E.)
| | - Daiana Bozgan
- Clinic of Neonatology, “Pius Brânzeu” County Emergency Clinical Hospital, 300723 Timișoara, Romania;
| | - Anda Nanu
- Third Pediatric Clinic, “Louis Țurcanu” Emergency Children Hospital, 300011 Timișoara, Romania; (A.N.); (I.S.)
| | - Iuliana Sîrbu
- Third Pediatric Clinic, “Louis Țurcanu” Emergency Children Hospital, 300011 Timișoara, Romania; (A.N.); (I.S.)
| | - Otilia Mărginean
- First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (O.B.); (O.M.)
- Department of Pediatrics, First Pediatric Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Ileana Enătescu
- Twelfth Department, Neonatology Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (M.P.); (I.E.)
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Arora U, Kedia S, Ahuja V. The practice of fecal microbiota transplantation in inflammatory bowel disease. Intest Res 2024; 22:44-64. [PMID: 37981746 PMCID: PMC10850701 DOI: 10.5217/ir.2023.00085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/10/2023] [Accepted: 09/14/2023] [Indexed: 11/21/2023] Open
Abstract
Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.
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Affiliation(s)
- Umang Arora
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Filip SS, Slivka RM, Bratasiuk AM, Skrypynets YP, Shitev AI. Pseudomembranous colitis as a complication in Covid-19. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2024; 77:450-455. [PMID: 38691786 DOI: 10.36740/wlek202403112] [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: 05/03/2024]
Abstract
OBJECTIVE Aim: To improve the results of treatment of patients with pseudomembranous colitis against the background of coronavirus infection. PATIENTS AND METHODS Materials and Methods: The study presents the results of a retrospective analysis of 96 patients with pseudomembranous colitis, who were treated in the infectious Covid department at the base of the Uzhhorod City Clinical Hospital since 2020 to 2022. The average age of patients was 55.2 years, there were 38 (39.5%) men and 58 (60.5%) women. Diagnosis of complications - pseudomembranous colitis (PMC) - was based on clinical data, ultrasound and CT of the abdominal organs, fibrocolonoscopy, laparoscopy. RESULTS Results: The frequency of PMC from the total number of patients who were in hospital treatment (8205 patients) due to COVID-19 was 1.17%, and this indicator was 0.62% in 2020, and 2.28% in 2021. Indications for operative treatment were: colon perforation - 9.4% of patients; peritonitis (diffuse, widespread) without obvious perforation of the colon wall - 85.5% of patients; mesenteric thrombosis - 4.1% of patients. In the case of perforation of the colon, resection of the colon was performed with the formation of a proximal colostomy and ileostomy. In case of mesenteric thrombosis, resection of the affected part of the small intestine was performed. In case of peritonitis without clear intraoperative detection of perforation of the colon wall, intraoperative lavage was performed. CONCLUSION Conclusions: 1) The frequency of detection of PMC in patients with COVID-19 in 2020 was 0.62%, and in 2021 - 2.28%. 2) The sensitivity of CT in the diagnosis of surgical complications of PMC was 72%, and the specificity was 58%. 3) Conservative treatment was effective in patients with PMC in 88.8% of cases, 21.2% had complications that required emergency surgical interventions. 4) The total mortality in patients with PMC was 11.36%, although this indicator was significantly higher in the event of surgical complications and operative treatment (22.4%).
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Marzoog BA. Gastrointestinal Tract and Kidney Injury Pathogenesis in Post-COVID-19 Syndrome. Curr Diabetes Rev 2024; 20:e051023221787. [PMID: 37815187 DOI: 10.2174/0115733998250889230919185305] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 06/20/2023] [Accepted: 07/18/2023] [Indexed: 10/11/2023]
Abstract
COVID-19 is a global health emergency that requires worldwide collaboration to control its spread. The scientific community is working to understand the different aspects of the post-COVID-19 syndrome and potential treatment strategies. Interestingly, there have been reports of gastrointestinal tract (GIT) involvement in the post-COVID-19 syndrome, suggesting the presence of both severe and mild GIT disorders. The development of the post-COVID-19- GIT syndrome involves various factors, such as impaired GIT mucosa cells, disruptions in the feeling of satiety, reduced blood supply due to the formation of small blood clots, and increased prostaglandin secretion caused by an excessive immune response. GIT symptoms have been observed in around 16% of COVID-19 patients. Other complications include kidney damage and prolonged impairment in the filtration and excretion functions of the glomeruli and tubules. The pathogenesis of post-COVID-19 renal syndrome involves factors, like an overactive immune response, reduced lung perfusion and oxygenation, viral infection in kidney tissues, endothelial dysfunction, and decreased blood volume. Roughly 20% of hospitalized patients experience renal manifestations after recovering from COVID-19.
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Affiliation(s)
- Basheer Abdullah Marzoog
- World-Class Research Center, Digital Biodesign and Personalized Healthcare, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
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Luo H, Luo D, Tang Q, Niu Z, Xu J, Li J. The combined impact of social networks and connectedness on anxiety, stress, and depression during COVID-19 quarantine: a retrospective observational study. Front Public Health 2023; 11:1298693. [PMID: 38169600 PMCID: PMC10758457 DOI: 10.3389/fpubh.2023.1298693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 12/01/2023] [Indexed: 01/05/2024] Open
Abstract
Introduction The COVID-19 pandemic and associated quarantine measures have precipitated a surge in mental health disorders, particularly depression and anxiety. Government policies and restrictions on physical activity have contributed to this phenomenon, as well as diminished subjective social connectedness and exacerbated objective social isolation. As two dimensions of social isolation, it is worth noting that subjectively perceived social connectedness serves as a protective factor for mental health, whereas the decline in the size of objectively evaluated social networks poses a significant risk. However, research investigating the combined influence of these two dimensions remains limited. Methods This study used an online survey to collect data to investigate the effects of objective social connectedness and objective social networks on anxiety, stress, and depression during COVID-19 quarantine. A total of 485 participants were analyzed using statistical methods, including paired t-test, Pearson correlation analysis, linear regression, cluster analysis, ANOVA, and moderated mediated. Results The study found that anxiety and depression scores increased during the quarantine, with age, education, and social connectedness scores associated with the increase. Pre-quarantine anxiety and depression levels were strongly correlated with mental health status during quarantine. Cluster analysis, respectively, revealed three clusters for those without increasing anxiety and depression scores. The study also found that objective social network influences the impact of subjective social connectedness on pre-quarantine mental health, which in turn affects anxiety and depression levels during quarantine. Conclusion The study identified that quarantine increased anxiety and depression, with age being protective, and education and subjective social connectedness as risk factors. The study also emphasizes the comprehensive impact of objective and subjective social isolation. Although individuals perceive the same degree of social connectedness, those with smaller social networks are more prone to developing symptoms of anxiety and depression, which are also more likely to worsen during quarantine.
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Affiliation(s)
| | | | | | | | - Jiajun Xu
- Mental Health Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jing Li
- Mental Health Center, West China Hospital, Sichuan University, Chengdu, China
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Mullish BH, Tohumcu E, Porcari S, Fiorani M, Di Tommaso N, Gasbarrini A, Cammarota G, Ponziani FR, Ianiro G. The role of faecal microbiota transplantation in chronic noncommunicable disorders. J Autoimmun 2023; 141:103034. [PMID: 37087392 DOI: 10.1016/j.jaut.2023.103034] [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: 01/17/2023] [Revised: 03/09/2023] [Accepted: 03/17/2023] [Indexed: 04/24/2023]
Abstract
The gut microbiome plays a key role in influencing several pathways and functions involved in human health, including metabolism, protection against infection, and immune regulation. Perturbation of the gut microbiome is recognised as a pathogenic factor in several gastrointestinal and extraintestinal disorders, and is increasingly considered as a therapeutic target in these conditions. Faecal microbiota transplantation (FMT) is the transfer of the microbiota from healthy screened stool donors into the gut of affected patients, and is a well-established and highly effective treatment for recurrent Clostridioides difficile infection. Despite the mechanisms of efficacy of FMT not being fully understood, it has been investigated in several chronic noncommunicable disorders, with variable results. This review aims to give an overview of mechanisms of efficacy of FMT in chronic noncommunicable disorders, and to paint the current landscape of its investigation in these medical conditions, including inflammatory bowel disease (IBD), chronic liver disorders, and also extraintestinal autoimmune conditions.
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Affiliation(s)
- Benjamin H Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK; Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Ege Tohumcu
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Serena Porcari
- Department of Medical and Surgical Sciences, Gastroenterology Unit, 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 Fiorani
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Natalia Di Tommaso
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Gastroenterology Unit, 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, Gastroenterology Unit, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Francesca Romana Ponziani
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Gianluca Ianiro
- Department of Medical and Surgical Sciences, Gastroenterology Unit, 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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Porcari S, Severino A, Rondinella D, Bibbò S, Quaranta G, Masucci L, Maida M, Scaldaferri F, Sanguinetti M, Gasbarrini A, Cammarota G, Ianiro G. Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis. J Autoimmun 2023; 141:103033. [PMID: 37085337 DOI: 10.1016/j.jaut.2023.103033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 03/05/2023] [Accepted: 03/17/2023] [Indexed: 04/23/2023]
Abstract
AIMS Clostridioides difficile infection (CDI) is a major challenge for healthcare systems. Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a risk factor for primary and recurrent CDI (rCDI). Moreover, CDI itself often worsens the clinical picture of IBD, increasing the risk of complications. Fecal microbiota transplantation (FMT) is a highly effective treatment for rCDI, but data from patients with IBD and CDI are limited and often referred to mixed cohorts. We aimed to report outcomes from a cohort of patients with UC treated with FMT for rCDI superinfection. METHODS AND RESULTS In a retrospective, single-centre cohort study we evaluated characteristics and outcomes of patients with UC who received FMT for rCDI. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Thirty-five patients were included in the analysis. Sixteen patients were cured after single FMT, while 19 patients received repeat FMT. Overall, FMT cured rCDI in 32 patients (91%), and repeat FMT was significantly associated with sustained cure of CDI compared with single FMT (84% vs 50%, p = 0.018). Twenty-four patients (69%) experienced remission or an amelioration of UC activity. Serious adverse events were not observed. CONCLUSIONS In our cohort of patients with UC, FMT was highly effective in curing rCDI without severe adverse events and repeat FMT was significantly associated with CDI cure. Most patients also experienced remission or amelioration of UC activity after FMT. Our findings suggest that a sequential FMT protocol may be used routinely in patients with UC and rCDI.
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Affiliation(s)
- Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Severino
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Debora Rondinella
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Stefano Bibbò
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Quaranta
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital, Caltanissetta, Italy
| | - Franco Scaldaferri
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
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Chang T, Lee K, Lee P, Wang Y, Lin Y, Huang H, Luo J, Ho H, Huang Y, Hou M. Assuring safety of fecal microbiota transplantation in the COVID-19 era: A single-center experience. JGH Open 2023; 7:765-771. [PMID: 38034050 PMCID: PMC10684976 DOI: 10.1002/jgh3.12979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 09/24/2023] [Accepted: 09/28/2023] [Indexed: 12/02/2023]
Abstract
Background and Aim Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan. Methods Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan. Results A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic. Conclusion Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products.
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Affiliation(s)
- Tien‐En Chang
- Division of Gastroenterology and HepatologyTaipei Veterans General HospitalTaipeiTaiwan
- Endoscopic Center for Diagnosis and TherapyTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Kuei‐Chuan Lee
- Division of Gastroenterology and HepatologyTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Pei‐Chang Lee
- Division of Gastroenterology and HepatologyTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Yen‐Po Wang
- Division of Gastroenterology and HepatologyTaipei Veterans General HospitalTaipeiTaiwan
- Endoscopic Center for Diagnosis and TherapyTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Yi‐Tsung Lin
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Division of Infectious DiseasesTaipei Veterans General HospitalTaipeiTaiwan
| | - Hui‐Chun Huang
- Division of Gastroenterology and HepatologyTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Division of General Medicine, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
| | - Jiing‐Chyuan Luo
- Division of Gastroenterology and HepatologyTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Healthcare and Services CenterTaipei Veterans General HospitalTaipeiTaiwan
| | - Hsiang‐Ling Ho
- Department of Pathology and Laboratory MedicineTaipei Veterans General HospitalTaipeiTaiwan
| | - Yi‐Hsiang Huang
- Division of Gastroenterology and HepatologyTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Ming‐Chih Hou
- Division of Gastroenterology and HepatologyTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
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Moreno-Corona NC, López-Ortega O, Pérez-Martínez CA, Martínez-Castillo M, De Jesús-González LA, León-Reyes G, León-Juárez M. Dynamics of the Microbiota and Its Relationship with Post-COVID-19 Syndrome. Int J Mol Sci 2023; 24:14822. [PMID: 37834270 PMCID: PMC10573029 DOI: 10.3390/ijms241914822] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/24/2023] [Accepted: 09/28/2023] [Indexed: 10/15/2023] Open
Abstract
Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies.
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Affiliation(s)
- Nidia Carolina Moreno-Corona
- Laboratory of Human Lymphohematopoiesis, Imagine Institute, INSERM UMR 1163, Université de Paris, 75015 Paris, France;
| | - Orestes López-Ortega
- Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institute Necker Enfants Malades, 75015 Paris, France;
| | | | - Macario Martínez-Castillo
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
| | | | - Guadalupe León-Reyes
- Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica (INMEGEN), México City 16610, Mexico;
| | - Moisés León-Juárez
- Laboratorio de Virología Perinatal y Diseño Molecular de Antígenos y Biomarcadores, Departamento de Inmunobioquímica, Instituto Nacional de Perinatología, Mexico City 11000, Mexico
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11
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Boicean A, Birlutiu V, Ichim C, Anderco P, Birsan S. Fecal Microbiota Transplantation in Inflammatory Bowel Disease. Biomedicines 2023; 11:biomedicines11041016. [PMID: 37189634 DOI: 10.3390/biomedicines11041016] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/21/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn’s disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host’s immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.
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12
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Del Barrio M, Lavín L, Santos-Laso Á, Arias-Loste MT, Odriozola A, Rodriguez-Duque JC, Rivas C, Iruzubieta P, Crespo J. Faecal Microbiota Transplantation, Paving the Way to Treat Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2023; 24:ijms24076123. [PMID: 37047094 PMCID: PMC10094628 DOI: 10.3390/ijms24076123] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/12/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent cause of chronic liver disease (CLD). Currently, the only therapeutic recommendation available is a lifestyle change. However, adherence to this approach is often difficult to guarantee. Alteration of the microbiota and an increase in intestinal permeability seem to be key in the development and progression of NAFLD. Therefore, the manipulation of microbiota seems to provide a promising therapeutic strategy. One way to do so is through faecal microbiota transplantation (FMT). Here, we summarize the key aspects of FMT, detail its current indications and highlight the most recent advances in NAFLD.
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Affiliation(s)
- María Del Barrio
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain
| | - Lucía Lavín
- Clinical Trial Agency Valdecilla-IDIVAL, Marqués de Valdecilla University Hospital, Av. Valdecilla, 25, 39008 Santander, Cantabria, Spain
| | - Álvaro Santos-Laso
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain
| | - Maria Teresa Arias-Loste
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain
| | - Aitor Odriozola
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain
| | - Juan Carlos Rodriguez-Duque
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain
| | - Coral Rivas
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain
| | - Paula Iruzubieta
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain
| | - Javier Crespo
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain
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13
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Mahmoudi H, Hossainpour H. Application and development of fecal microbiota transplantation in the treatment of gastrointestinal and metabolic diseases: A review. Saudi J Gastroenterol 2023; 29:3-11. [PMID: 36412458 PMCID: PMC10117003 DOI: 10.4103/sjg.sjg_131_22] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Fecal microbiota transplantation (FMT) restores a balanced intestinal flora, which helps to cure recurrent Clostridium difficile infections (RCDI). FMT has also been used to treat other gastrointestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation, as well as a variety of non-GI disorders. The purpose of this review is to discuss gut microbiota and FMT treatment of GI and non-GI diseases. An imbalanced gut microbiota is known to predispose one to Clostridium difficile infections (CDI), IBD, and IBS. However, the complex role of the gut microbiota in maintaining health is a newer concept that is being increasingly studied. The microbiome plays a major role in cellular immunity and metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity, and even some neuropsychiatric disorders. Many recent studies have reported that viral gastroenteritis can affect intestinal epithelial cells, and SARS-CoV-2 virus has been identified in the stool of infected patients. FMT is a highly effective cure for RCDI, but a better understanding of the gut microbiota in maintaining health and controlled studies of FMT in a variety of conditions are needed before FMT can be accepted and used clinically.
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Affiliation(s)
- Hassan Mahmoudi
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences; Department of Nursing and Paramedical, Nahavand School of Allied Medical Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hadi Hossainpour
- Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
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14
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Bachour SP, Dalal R, Allegretti JR. The impact of the COVID-19 pandemic on Clostridioides difficile infection and utilization of fecal microbiota transplantation. Therap Adv Gastroenterol 2023; 16:17562848231165581. [PMID: 37091531 PMCID: PMC10107020 DOI: 10.1177/17562848231165581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 03/06/2023] [Indexed: 04/25/2023] Open
Abstract
Previous research has demonstrated that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains cell entry through the angiotensin-converting enzyme 2 receptor, which is abundantly found throughout the gastrointestinal (GI) tract, resulting in a wide array of GI manifestations of coronavirus disease 2019 (COVID-19). By gaining entry into the intestinal epithelial and stromal cells, SARS-CoV-2 has been observed to cause intestinal inflammation and gut dysbiosis. Alterations in gut microbiota are known to be involved in the pathophysiology of Clostridioides difficile infection (CDI). During the initial stages of the COVID-19 pandemic, rates of CDI were similar to historical data despite the increased use of antibiotics. This may be due to increased emphasis on hygiene and protective equipment and reduced C. difficile testing as diarrhea was presumed to be COVID-19 related. Studies also demonstrated additional risk factors for CDI in COVID-19 patients, including length of hospitalization and new abdominal pain during admission. Although not associated with increased mortality, CDI was associated with increased length of hospital stay among patients admitted with COVID-19. Due to fecal viral shedding and concern of oral-fecal transmission of SARS-CoV-2, increased safety regulations were introduced to fecal microbiota transplantation (FMT) leading to reduced rates of this procedure during the COVID-19 pandemic. FMT for recurrent CDI during the COVID-19 pandemic remained highly effective without any reports of SARS-CoV-2 transmission. In addition, limited data show that FMT may be effective in treating COVID-19 and restoring healthy gut microbiota. The goal of this article is to review the impact that the COVID-19 pandemic has had on hospital-acquired CDI and the utilization of FMT.
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Affiliation(s)
- Salam P. Bachour
- Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Rahul Dalal
- Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA, USA
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15
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Sridhar J, Parit R, Boopalakrishnan G, Rexliene MJ, Praveen R, Viswananathan B. Importance of wastewater-based epidemiology for detecting and monitoring SARS-CoV-2. CASE STUDIES IN CHEMICAL AND ENVIRONMENTAL ENGINEERING 2022; 6:100241. [PMID: 37520919 PMCID: PMC9341170 DOI: 10.1016/j.cscee.2022.100241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 07/26/2022] [Accepted: 07/27/2022] [Indexed: 08/01/2023]
Abstract
Coronavirus disease caused by the SARS-CoV-2 virus has emerged as a global challenge in terms of health and disease monitoring. COVID-19 infection is mainly spread through the SARS-CoV-2 infection leading to the development of mild to severe clinical manifestations. The virus binds to its cognate receptor ACE2 which is widely expressed among different tissues in the body. Notably, SARS-CoV-2 shedding in the fecal samples has been reported through the screening of sewage water across various countries. Wastewater screening for the presence of SARS-CoV-2 provides an alternative method to monitor infection threat, variant identification, and clinical evaluation to restrict the virus progression. Multiple cohort studies have reported the application of wastewater treatment approaches and epidemiological significance in terms of virus monitoring. Thus, the manuscript outlines consolidated and systematic information regarding the application of wastewater-based epidemiology in terms of monitoring and managing a viral disease outbreak like COVID-19.
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Affiliation(s)
- Jayavel Sridhar
- Department of Biotechnology (DDE), Madurai Kamaraj University, Madurai, 625021, Tamilnadu, India
| | - Rahul Parit
- Department of Biotechnology (DDE), Madurai Kamaraj University, Madurai, 625021, Tamilnadu, India
| | | | - M Johni Rexliene
- Department of Biotechnology (DDE), Madurai Kamaraj University, Madurai, 625021, Tamilnadu, India
| | - Rajkumar Praveen
- Department of Biotechnology (DDE), Madurai Kamaraj University, Madurai, 625021, Tamilnadu, India
| | - Balaji Viswananathan
- Department of Biotechnology (DDE), Madurai Kamaraj University, Madurai, 625021, Tamilnadu, India
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Mazzawi T, Hausken T, Refsnes PF, Hatlebakk JG, Lied GA. The Effect of Anaerobically Cultivated Human Intestinal Microbiota Compared to Fecal Microbiota Transplantation on Gut Microbiota Profile and Symptoms of Irritable Bowel Syndrome, a Double-Blind Placebo-Controlled Study. Microorganisms 2022; 10:microorganisms10091819. [PMID: 36144420 PMCID: PMC9503104 DOI: 10.3390/microorganisms10091819] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/04/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension (n = 17), donor-FMT (n = 11), or placebo (n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.
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Affiliation(s)
- Tarek Mazzawi
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
- Faculty of Medicine, Al-Balqa Applied University, 19117 Al-Salt, Jordan
- Correspondence:
| | - Trygve Hausken
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Per Førde Refsnes
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Jan Gunnar Hatlebakk
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Gülen Arslan Lied
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
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17
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Qu Z, Tian P, Yang B, Zhao J, Wang G, Chen W. Fecal microbiota transplantation for diseases: Therapeutic potential, methodology, risk management in clinical practice. Life Sci 2022; 304:120719. [PMID: 35716734 DOI: 10.1016/j.lfs.2022.120719] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/02/2022] [Accepted: 06/12/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND More than 95 % of human diseases may be related to the disturbance of gut microbes. As a treatment method that extensively regulates the gut microbes, fecal microbiota transplantation (FMT) has proven to be an effective therapy for some diseases, becoming a topic of interest among clinicians, patients and scientists. AIM To review the latest clinical research results of FMT in the treatment of various diseases and the methodology and risk management in clinical application. METHODS Search PubMed and Web of Science for reliable research results of clinical treatment of FMT within 5-10 years, as well as application guidelines and risk management policies in different regions. RESULTS As a measure of allogeneic/autologous microbiota transplantation, FMT has been used to treat a variety of diseases. By reviewing the clinical studies of FMT in gastrointestinal diseases, metabolic diseases, neurological diseases and malignant tumors, the various mechanisms in the treatment of diseases are summarized. Such as regulation of receptor microbiota composition, specific metabolites, phage function and immune response. In addition, potential risk factors, donor stool screening indicators, recipient self-specificity and possible prognostic marker molecules in the course of FMT treatment were generalized. CONCLUSIONS The potential regulatory mechanisms, risk factors and targets of FMT in gastrointestinal diseases, metabolic diseases, malignancies and neurological diseases were reviewed and proposed. It provides a theoretical basis for the establishment of a standardized treatment system for FMT and a breakthrough in treatment technology.
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Affiliation(s)
- Zhihao Qu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Peijun Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Bo Yang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China.
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
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18
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Wang Y, Zhang S, Borody TJ, Zhang F. Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases. Chin Med J (Engl) 2022; 135:1927-1939. [PMID: 36103991 PMCID: PMC9746749 DOI: 10.1097/cm9.0000000000002339] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Indexed: 01/06/2023] Open
Abstract
ABSTRACT Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT from a global perspective. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota-gut-liver axis, microbiota-gut-brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.
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Affiliation(s)
- Yun Wang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu 210011, China
| | - Sheng Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu 210011, China
| | | | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu 210011, China
- National Clinical Research Center for Digestive Diseases, Xi’an, Shaanxi 710032, China
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Concas G, Barone M, Francavilla R, Cristofori F, Dargenio VN, Giorgio R, Dargenio C, Fanos V, Marcialis MA. Twelve Months with COVID-19: What Gastroenterologists Need to Know. Dig Dis Sci 2022; 67:2771-2791. [PMID: 34333726 PMCID: PMC8325547 DOI: 10.1007/s10620-021-07158-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 07/06/2021] [Indexed: 02/07/2023]
Abstract
Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal-oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care.
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Affiliation(s)
- Giulia Concas
- School of Paediatrics, University of Cagliari, 09124 Cagliari, Italy
| | - Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, University Hospital “Policlinico”, Piazza G. Cesare 11, 70124 Bari, Italy
| | - Ruggiero Francavilla
- Department of Biomedical Science and Human Oncology, Children’s Hospital “Giovanni XXIII”, University of Bari, 70126 Bari, Italy
| | - Fernanda Cristofori
- Department of Biomedical Science and Human Oncology, Children’s Hospital “Giovanni XXIII”, University of Bari, 70126 Bari, Italy
| | - Vanessa Nadia Dargenio
- Department of Biomedical Science and Human Oncology, Children’s Hospital “Giovanni XXIII”, University of Bari, 70126 Bari, Italy
| | - Rossella Giorgio
- Department of Biomedical Science and Human Oncology, Children’s Hospital “Giovanni XXIII”, University of Bari, 70126 Bari, Italy
| | - Costantino Dargenio
- Department of Biomedical Science and Human Oncology, Children’s Hospital “Giovanni XXIII”, University of Bari, 70126 Bari, Italy
| | - Vassilios Fanos
- Neonatal Intensive Care Unit, Azienda Ospedaliero Universitaria, University of Cagliari, Cagliari, 09124 Cagliari, Italy
| | - Maria Antonietta Marcialis
- Neonatal Intensive Care Unit, Azienda Ospedaliero Universitaria, University of Cagliari, Cagliari, 09124 Cagliari, Italy
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20
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Takáčová M, Bomba A, Tóthová C, Micháľová A, Turňa H. Any Future for Faecal Microbiota Transplantation as a Novel Strategy for Gut Microbiota Modulation in Human and Veterinary Medicine? Life (Basel) 2022; 12:723. [PMID: 35629390 PMCID: PMC9146664 DOI: 10.3390/life12050723] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/28/2022] [Accepted: 05/10/2022] [Indexed: 11/16/2022] Open
Abstract
Alterations in the composition of the intestinal microbiome, also known as dysbiosis, are the result of many factors such as diet, antibiotics, stress, diseases, etc. There are currently several ways to modulate intestinal microbiome such as dietary modulation, the use of antimicrobials, prebiotics, probiotics, postbiotics, and synbiotics. Faecal microbiota transplantation (FMT) represents one new method of gut microbiota modulation in humans with the aim of reconstructing the intestinal microbiome of the recipient. In human medicine, this form of bacteriotherapy is successfully used in cases of recurrent Clostridium difficile infection (CDI). FMT has been known in large animal medicine for several years. In small animal medicine, the use of FMT is not part of normal practice.
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Affiliation(s)
- Martina Takáčová
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
| | - Alojz Bomba
- Prebiotix s.r.o., 024 01 Kysucké Nové Mesto, Slovakia
| | - Csilla Tóthová
- Clinic of Ruminants, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
| | - Alena Micháľová
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
| | - Hana Turňa
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
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21
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Linares-García L, Cárdenas-Barragán ME, Hernández-Ceballos W, Pérez-Solano CS, Morales-Guzmán AS, Miller DS, Schmulson M. Bacterial and Fungal Gut Dysbiosis and Clostridium difficile in COVID-19: A Review. J Clin Gastroenterol 2022; 56:285-298. [PMID: 35125404 PMCID: PMC8900892 DOI: 10.1097/mcg.0000000000001669] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Gastrointestinal symptoms are common in Coronavirus Disease 2019 (COVID-19), related to infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) of intestinal cells through the angiotensin converting enzyme 2 (ACE2) receptor in the brush border. Also, patients are treated with multiple antibiotics. Therefore, an increase in gut dysbiosis and in the prevalence of Clostridium difficile infection (CDI) is expected in patients with COVID-19. METHODS A PubMed search was conducted using the terms "gut microbiota," "gut mycobiota," "dysbiosis" AND "COVID-19"; "Clostridium difficile," "Clostridioides difficile" AND "COVID-19"; "probiotics," "bacteriotherapy AND COVID-19." Only case series, observational and experimental studies were included. RESULTS A total of 384 papers were retrieved and 21 fulfilled selection criteria. Later, a new paper was identified, thus 22 papers were reviewed. Main findings: (1) gut bacterial dysbiosis has been found in fecal samples of COVID-19 patients, with enrichment of opportunistic organisms and decrease of beneficial commensals such as Faecalibacterium prausnitizii. Dysbiosis is related to inflammatory markers and illness severity. (2) There is evidence for abnormal gut barrier and bacterial translocation with a negative impact in the lungs. (3) Fungal dysbiosis correlating with pulmonary mycobiota, has also been found. (4) There is controversy in the CDI rates among COVID-19 patients versus controls and pandemic versus prepandemic era. (5) There is no available evidence yet to support bacteriotherapy in COVID-19. (6) Fecal microbiota transplantation (FMT) has been proposed for COVID-19, although there is no evidence to support it. Also, FMT can be safely used during the pandemic for CDI if strict screening protocols for donors and fecal product are implemented. CONCLUSIONS In COVID-19 there is bacterial and fungal dysbiosis that correlates with systemic and pulmonary inflammation, and illness severity. Further investigations are warranted to determine the efficacy of bacteriotherapy and FMT for modulating gut dysbiosis in COVID-19.
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Affiliation(s)
- Laura Linares-García
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM)
| | - María E. Cárdenas-Barragán
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM)
| | - Winston Hernández-Ceballos
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM)
- Program of Combined Studies in Medicine. Faculty of Medicine-Universidad Nacional Autónoma de México (UNAM), Mexico City, México
| | - Carlos S. Pérez-Solano
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM)
- Program of Combined Studies in Medicine. Faculty of Medicine-Universidad Nacional Autónoma de México (UNAM), Mexico City, México
| | - Alizon S. Morales-Guzmán
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM)
| | | | - Max Schmulson
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM)
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22
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Groenewegen B, van Lingen E, Ooijevaar RE, Wessels E, Feltkamp MCW, Boeije-Koppenol E, Verspaget HW, Kuijper EJ, van Prehn J, Keller JJ, Terveer EM. How to prepare stool banks for an appropriate response to the ongoing COVID-19 pandemic: Experiences in the Netherlands and a retrospective comparative cohort study for faecal microbiota transplantation. PLoS One 2022; 17:e0265426. [PMID: 35298520 PMCID: PMC8929558 DOI: 10.1371/journal.pone.0265426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 03/02/2022] [Indexed: 12/02/2022] Open
Abstract
Background Faecal microbiota transplantation (FMT) is an efficacious treatment for patients with recurrent Clostridioides difficile infections (rCDI). Stool banks facilitate FMT by providing screened faecal suspensions from highly selected healthy donors. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic and the potential risk of SARS coronavirus-2 (SARS-CoV-2) transmission via FMT, many stool banks were forced to temporarily halt and adjust donor activities. Goal The evaluation of a strategy to effectively continue stool banking activities during the ongoing COVID-19 pandemic. Study To restart our stool banking activities after an initial halt, we implemented periodic SARS-CoV-2 screening in donor faeces and serum, and frequent donor assessment for COVID-19 related symptoms. FMT donor and recipient data obtained before (2016–2019) and during the COVID-19 pandemic (March 2020-August 2021) were compared to assess stool banking efficacy. Results Two out of ten donors developed COVID-19. No differences during versus before the COVID-19 pandemic were observed in the number of approved faeces donations (14 vs 22/month, p = 0.06), FMT requests for rCDI (3.9 vs 4.3/month, p = 0.6); rCDI patients eligible for FMT (80.6% vs 73.3%, p = 0.2); rCDI cure rate (90.3% vs 89.2%, p = 0.9); CDI-free survival (p = 0.7); the number of non-rCDI patients treated with FMT (0.5/month vs 0.4/month), and the number of possibly FMT related adverse events (9.5% vs 7.8%, p = 0.7). Two FMTs for rCDI were delayed due to COVID-19. Conclusions There is a continued need for FMT treatment of rCDI during the COVID-19 pandemic. Appropriate donor screening and SARS-CoV-2 infection prevention measures can be implemented in existing protocols without increasing the burden for donors, and allow safe, effective and efficient FMT during the ongoing COVID-19 pandemic. Stool banks should evaluate their SARS-CoV-2 donor screening protocols for long-term sustainability and efficacy, and share their experiences to help the utilisation, standardisation and improvement of stool banks worldwide.
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Affiliation(s)
- Bas Groenewegen
- Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Emilie van Lingen
- Department of Gastroenterology and Hepatology, LUMC, Leiden, The Netherlands
| | - Rogier E. Ooijevaar
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, VU University Medical Center, Amsterdam, The Netherlands
| | - Els Wessels
- Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Mariet C. W. Feltkamp
- Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Eline Boeije-Koppenol
- Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Hein W. Verspaget
- Department of Gastroenterology and Hepatology, LUMC, Leiden, The Netherlands
- Department of Biobanking, LUMC, Leiden, The Netherlands
| | - Ed J. Kuijper
- Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
- Reference Laboratory for C. difficile, LUMC and RIVM (Center for Infectious Disease Control, National Institute for Public Health and the Environment), Bilthoven, The Netherlands
| | - Joffrey van Prehn
- Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Josbert J. Keller
- Department of Gastroenterology and Hepatology, LUMC, Leiden, The Netherlands
- Department of Gastroenterology, Haaglanden Medical Center, Den Haag, The Netherlands
| | - Elisabeth M. Terveer
- Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
- * E-mail:
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23
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Waller KMJ, Leong RW, Paramsothy S. An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases. J Gastroenterol Hepatol 2022; 37:246-255. [PMID: 34735024 DOI: 10.1111/jgh.15731] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 10/17/2021] [Accepted: 10/18/2021] [Indexed: 12/13/2022]
Abstract
Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.
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Affiliation(s)
- Karen M J Waller
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.,Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.,Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.,Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Sudarshan Paramsothy
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.,Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.,Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
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24
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Ianiro G, Bibbò S, Porcari S, Settanni CR, Giambò F, Curta AR, Quaranta G, Scaldaferri F, Masucci L, Sanguinetti M, Gasbarrini A, Cammarota G. Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center. Gut Microbes 2022; 13:1994834. [PMID: 34709989 PMCID: PMC8555518 DOI: 10.1080/19490976.2021.1994834] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event.FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.
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Affiliation(s)
- Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy,CONTACT Gianluca Ianiro Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Largo A. Gemelli 8, Rome00168, Italy
| | - Stefano Bibbò
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Carlo Romano Settanni
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Federica Giambò
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Andreea Roxana Curta
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Gianluca Quaranta
- Microbiology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Franco Scaldaferri
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
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25
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Validation of Two Commercial Multiplex Real-Time PCR Assays for Detection of SARS-CoV-2 in Stool Donors for Fecal Microbiota Transplantation. Microorganisms 2022; 10:microorganisms10020284. [PMID: 35208740 PMCID: PMC8879890 DOI: 10.3390/microorganisms10020284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/21/2022] [Accepted: 01/23/2022] [Indexed: 12/14/2022] Open
Abstract
Recurrent infection by Clostridioides difficile has recently been treated by fecal microbiota transplantation (FMT). As viable SARS-CoV-2 was recovered from stool of asymptomatic individuals, the FMT procedure could be a potential risk of SARS-CoV-2 transmission, thus underlying the need to reliably detect SARS-CoV-2 in stool. Here, we performed a multicentric study to explore performances of two commercially available assays for detection of SARS-CoV-2 RNA in stool of potential FMT donors. In three hospitals, 180 stool samples were spiked with serial 10-fold dilutions of a SARS-CoV-2 inactivated lysate to evaluate the Seegene Allplex™ SARS-CoV-2 (SC2) and SARS-CoV-2/FluA/FluB/RSV (SC2FABR) Assays for the detection of viral RNA in stool of FMT donors. The results revealed that both assays detected down to 2 TCID50/mL with comparable limit of detection values, SC2 showing more consistent target positivity rate than SC2FABR. Beyond high amplification efficiency, correlation between CT values and log concentrations of inactivated viral lysates showed R2 values ranging from 0.88 to 0.90 and from 0.87 to 0.91 for the SC2 and SC2FABR assay, respectively. The present results demonstrate that both methods are highly reproducible, sensitive, and accurate for SARS-CoV-2 RNA detection in stool, suggesting a potential use in FMT-donor screening.
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26
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Junca H, Pieper DH, Medina E. The emerging potential of microbiome transplantation on human health interventions. Comput Struct Biotechnol J 2022; 20:615-627. [PMID: 35140882 PMCID: PMC8801967 DOI: 10.1016/j.csbj.2022.01.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/06/2022] [Accepted: 01/08/2022] [Indexed: 02/08/2023] Open
Abstract
The human microbiome has been the subject of intense research over the past few decades, in particular as a promising area for new clinical interventions. The microbiota colonizing the different body surfaces are of benefit for multiple physiological and metabolic processes of the human host and increasing evidence suggests an association between disturbances in the composition and functionality of the microbiota and several pathological conditions. This has provided a rationale for beneficial modulation of the microbiome. One approach being explored for modulating the microbiota in diseased individuals is transferring microbiota or microbiota constituents from healthy donors via microbiome transplantation. The great success of fecal microbiome transplantation for the treatment of Clostridioides difficile infections has encouraged the application of this procedure for the treatment of other diseases such as vaginal disorders via transplantation of vaginal microbiota, or of skin pathologies via the transplantation of skin microbiota. Microbiome modulation could even become a novel strategy for improving the efficacy of cancer therapies. This review discusses the principle, advantages and limitations of microbiome transplantation as well as different clinical contexts where microbiome transplantation has been applied.
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Affiliation(s)
- Howard Junca
- Microbial Interactions and Processes Research Group, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
| | - Dietmar H. Pieper
- Microbial Interactions and Processes Research Group, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
| | - Eva Medina
- Infection Immunology Research Group, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
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27
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Wu LH, Ye ZN, Peng P, Xie WR, Xu JT, Zhang XY, Xia HHX, He XX. Efficacy and Safety of Washed Microbiota Transplantation to Treat Patients with Mild-to-Severe COVID-19 and Suspected of Having Gut Microbiota Dysbiosis: Study Protocol for a Randomized Controlled Trial. Curr Med Sci 2021; 41:1087-1095. [PMID: 34846698 PMCID: PMC8630278 DOI: 10.1007/s11596-021-2475-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 11/02/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD. METHODS This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated. RESULTS By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity. CONCLUSION The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.
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Affiliation(s)
- Li-hao Wu
- Department of Gastroenterology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
- Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
| | - Zhi-ning Ye
- Department of Gastroenterology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
- Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
| | - Ping Peng
- Guangzhou Eighth People’s Hospital, Guangzhou, 510060 China
| | - Wen-rui Xie
- Department of Gastroenterology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
- Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
| | - Jia-ting Xu
- Department of Gastroenterology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
- Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
| | - Xue-yuan Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
- Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
| | - Harry Hua-xiang Xia
- Department of Gastroenterology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
| | - Xing-xiang He
- Department of Gastroenterology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
- Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 China
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28
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He J, He X, Ma Y, Yang L, Fang H, Shang S, Xia H, Lian G, Tang H, Wang Q, Wang J, Lin Z, Wen J, Liu Y, Zhai C, Wang W, Jiang X, Xuan J, Liu M, Lu S, Li X, Wang H, Ouyang C, Cao M, Lin A, Zhang B, Wu D, Chen Y, Xiao C. A comprehensive approach to stool donor screening for faecal microbiota transplantation in China. Microb Cell Fact 2021; 20:216. [PMID: 34838016 PMCID: PMC8626716 DOI: 10.1186/s12934-021-01705-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 11/09/2021] [Indexed: 12/31/2022] Open
Abstract
Background Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China. Results The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time. Conclusions DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT. Supplementary Information The online version contains supplementary material available at 10.1186/s12934-021-01705-0.
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Affiliation(s)
- Jianquan He
- School of Medicine, Xiamen University, Xiamen, China
| | - Xingxiang He
- Department of Gastroenterology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China
| | - Yonghui Ma
- School of Medicine, Xiamen University, Xiamen, China
| | - Luxi Yang
- School of Medicine, Xiamen University, Xiamen, China
| | - Haiming Fang
- Department of Gastroenterology and Hepatology, The Second Hospital of Anhui Medical Univerisity, Hefei, China
| | - Shu Shang
- Department of Gastroenterology, The Fifth People's Hospital of Shenyang, Shenyang, China
| | - Huping Xia
- Anorectal Diagnosis and Treatment Center, The General Hospital of Xinjiang Military Region, Wulumuqi, China
| | - Guanghui Lian
- Department of Gastroenterology, Xiangya Hospital, Changsha, China
| | - Hailing Tang
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, China
| | - Qizhi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Junping Wang
- Department of Gastroenterology, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, China
| | - Zhihui Lin
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, China
| | - Jianbo Wen
- Department of Gastroenterology, Pingxiang People's Hospital, Pingxiang, China
| | - Yuedong Liu
- Department of Gastroenterology, The Third Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Chunbao Zhai
- Department of Proctology, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, China
| | - Wen Wang
- Department of Gastroenterology, 900th Hospital of PLA, Fuzhou, China
| | - Xueliang Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ji Xuan
- Department of Gastroenterology, Jinling Hospital, Nanjing, China
| | - Morong Liu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Shiyun Lu
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, China
| | - Xuejun Li
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Han Wang
- Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Cong Ouyang
- Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Man Cao
- Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Aiqiang Lin
- Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | | | - Depei Wu
- National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Ye Chen
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Ianiro G, Porcari S, Bibbò S, Giambò F, Quaranta G, Masucci L, Sanguinetti M, Gasbarrini A, Cammarota G. Donor program for fecal microbiota transplantation: A 3-year experience of a large-volume Italian stool bank. Dig Liver Dis 2021; 53:1428-1432. [PMID: 34030988 DOI: 10.1016/j.dld.2021.04.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 03/05/2021] [Accepted: 04/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Due to the increasing rise of C. difficile infection, stool banks and donor programs have been launched to grant access to fecal microbiota transplantation (FMT). Our aim is to describe characteristics and outcomes of the donor program at our stool bank. METHODS Donor candidates underwent a four-step selection process, including a clinical interview, blood and stool testing, a further questionnaire and a direct stool testing the day of each donation. From March 2020, specific changes to this process were introduced to avoid the potential transmission of COVID-19. We evaluated the rate of excluded candidates at each step of the screening, as well as the number of total fecal aliquots provided by qualified donors. RESULTS Overall, 114 donor candidates were evaluated. Seventy-five candidates declined to join the program for logistic or personal issues, three were excluded after the questionnaire and seven for positive stool exams. Finally, 29 (25%) subjects qualified as stool donors, and provided 70 stool samples. Fifteen samples were excluded after direct molecular stool testing. A total of 127 aliquots was finally obtained. CONCLUSIONS Donor recruitment for FMT is a challenging process, and only a small rate of candidates are eligible as donors.
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Affiliation(s)
- Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy
| | - Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy
| | - Stefano Bibbò
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy
| | - Federica Giambò
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy
| | - Gianluca Quaranta
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy
| | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo "A. Gemelli", 8, 00168, Rome, Italy.
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Sirinawasatien A, Chantarojanasiri T, Ekpanyapong S, Tivatunsakul N, Luvira V. Coronavirus disease 2019 gastrointestinal and liver manifestations in adults: A review. JGH Open 2021; 5:1257-1265. [PMID: 34816011 PMCID: PMC8593773 DOI: 10.1002/jgh3.12671] [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: 09/02/2021] [Revised: 10/09/2021] [Accepted: 10/12/2021] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is an important health problem that has a serious adverse impact on the global economy and healthcare systems. The virus is not only involved in the respiratory system, but also causes other systemic effects as well as several gastrointestinal and liver issues. Evidence has shown direct viral invasion into the gastrointestinal tissue and supporting vascular network, causing various manifestations such as diarrhea, nausea, gastrointestinal bleeding, and abnormal liver function tests. The degree of gastrointestinal injury, especially in terms of liver involvement, is correlated with disease severity. There is no specific treatment for gastrointestinal involvement, and the symptoms can be managed with supportive therapy. Moreover, increased liver decompensation and mortality can be found in COVID-19-infected patients with coexisting liver disease. As the virus can be identified in gastrointestinal contents, endoscopic procedures during the pandemic should be carefully selected and proper protection strategies should be encouraged to prevent viral transmission.
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Affiliation(s)
- Apichet Sirinawasatien
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of MedicineRungsit UniversityBangkokThailand
| | - Tanyaporn Chantarojanasiri
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of MedicineRungsit UniversityBangkokThailand
| | - Sirina Ekpanyapong
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of MedicineRungsit UniversityBangkokThailand
| | - Naris Tivatunsakul
- Division of Gastroenterology, Department of MedicineBanpong HospitalRatchaburiThailand
| | - Viravarn Luvira
- Department of Clinical Tropical Medicine, Faulty of Tropical MedicineMahidol UniversityBangkokThailand
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Yau YK, Mak WYJ, Lui NSR, Ng WYR, Cheung CYK, Li YLA, Ching YLJ, Chin ML, Lau HSL, Chan KLF, Chan KSP, Ng SC. High prevalence of extended-spectrum beta-lactamase organisms and the COVID-19 pandemic impact on donor recruitment for fecal microbiota transplantation in Hong Kong. United European Gastroenterol J 2021; 9:1027-1038. [PMID: 34623758 PMCID: PMC8598959 DOI: 10.1002/ueg2.12160] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 08/23/2021] [Accepted: 08/24/2021] [Indexed: 02/06/2023] Open
Abstract
Background With increasing number of clinical trials relating to fecal microbiota transplantation (FMT), it is crucial to identify and recruit long‐term, healthy, and regular fecal donors. Objective We aimed to report the outcomes of screening and recruitment of fecal donors for FMT. Methods Potential donors were recruited via advertisement through internal mass emails at a university. They were required to undergo a pre‐screening telephone interview, a detailed questionnaire, followed by blood and stool investigations. Results From January 2017 to December 2020, 119 potential donors were assessed with 75 failed pre‐screening. Reasons for failure included: inability to come back for regular and long‐term donation (n = 19), high body mass index (n = 17), underlying chronic illness or on long‐term medications (n = 11), being healthcare professionals (n = 10), use of antibiotics within 3 months (n = 5) and others (n = 13). Forty‐four donors completed questionnaires and 11 did not fulfill the clinical criteria. Of the remaining 33 potential donors who had stool and blood tests, 21 failed stool investigations (19 extended‐spectrum beta‐lactamase [ESBL] organisms, one Clostridioides difficile, one C. difficile plus Methicillin Resistant Staphylococcus aureus), one failed blood tests (high serum alkaline phosphatase level), one required long‐term medication and nine withdrew consent and/or lost to follow‐up. In total, only one out of 119 (0.8%) potential donors was successfully recruited as a regular donor. Conclusion There was a high failure rate in donor screening for FMT. Main reasons for screening failure included high prevalence of positive ESBL organisms in stool and failed commitment to regular stool donation.
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Affiliation(s)
- Yuk Kam Yau
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Wing Yan Joyce Mak
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Nok Shun Rashid Lui
- Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Wai Yin Rita Ng
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Choi Yan Kitty Cheung
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Ying Lee Amy Li
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yuet Ling Jessica Ching
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Miu Ling Chin
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Ho Shing Louis Lau
- Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Ka Leung Francis Chan
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Kay Sheung Paul Chan
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Siew Chien Ng
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
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Liu Y, Alnababtah K, Cook S, Yu Y. Healthcare providers' perception of faecal microbiota transplantation with clostridium difficile infection and inflammatory bowel disease: a quantitative systematic review. Therap Adv Gastroenterol 2021; 14:17562848211042679. [PMID: 34567271 PMCID: PMC8460966 DOI: 10.1177/17562848211042679] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 07/15/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are global gastroenterological diseases that cause considerable burden on human health, healthcare systems, and society. Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides Difficile Infection (rCDI) and a promising therapy for IBD. However, indication for FMT in IBD is still unofficial. Consequently, the National Institute for Health and Care Excellence (NICE) is seeking healthcare providers' advice on whether to update FMT guidelines. METHODS A systematic review methodology was adopted for this study. Five databases (CINAHL, MEDLINE, Cochrane Library, Scopus, Web of Science) and grey literature were systematically searched for English language literature to 14 May 2021. The quality of the included studies was then appraised using the Institute for Public Health Sciences cross-sectional studies tool, after which the findings of the studies were narratively synthesised. RESULTS Thirteen cross-sectional studies with 4110 validated questionnaire responses were included. Narrative synthesis found that 39.43% of respondents were familiar with FMT (N = 3746, 95%CI = 37.87%-41%), 58.81% of respondents would recommend FMT to their patients (N = 1141, 95%CI = 55.95%-61.67%), 66.67% of respondents considered lack of clinical evidence was the greatest concern regarding FMT (N = 1941, 95%CI = 64.57%-68.77%), and 40.43% respondents would not implement FMT due to concerns about infection transmission (N = 1128, 95%CI = 37.57%-43.29%). CONCLUSION Healthcare providers' knowledge of FMT is relatively low and education is an effective strategy to improve it. As knowledge of FMT increases, willingness to recommend it also increases. Strengthening FMT clinical efficacy and reducing infection can enhance its public acceptance, application and popularity. However, further research is required to explore the donor screening procedure.
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Affiliation(s)
- Yanghua Liu
- Department of Nursing, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China,Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, UK
| | - Kal Alnababtah
- Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, UK
| | - Simon Cook
- Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, UK
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The Role of Fecal Microbiota Transplantation in the Treatment of Inflammatory Bowel Disease. J Clin Med 2021; 10:jcm10184055. [PMID: 34575166 PMCID: PMC8465860 DOI: 10.3390/jcm10184055] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 12/12/2022] Open
Abstract
The exact pathogenesis of inflammatory bowel disease (IBD) is still not completely understood. It is hypothesized that a genetic predisposition leads to an exaggerated immune response to an environmental trigger, leading to uncontrolled inflammation. As there is no known causative treatment, current management strategies for inflammatory bowel disease focus on correcting the excessive immune response to environmental (including microbial) triggers. In recent years, there has been growing interest in new avenues of treatment, including targeting the microbial environment itself. Fecal microbiota transplantation (FMT) is a novel treatment modality showing promising results in early studies. The article discusses the rationale for the use of FMT in inflammatory bowel disease and the yet-unresolved questions surrounding its optimal use in practice.
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Nandwana V, Debbarma S. Fecal Microbiota Transplantation: A Microbiome Modulation Technique for Alzheimer's Disease. Cureus 2021; 13:e16503. [PMID: 34430117 PMCID: PMC8374998 DOI: 10.7759/cureus.16503] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/19/2021] [Indexed: 12/20/2022] Open
Abstract
Alzheimer’s disease (AD) is the most common form of dementia and the fifth leading cause of death among the elderly. AD involves parts of the brain that can lead to progressive memory loss and impaired language skills and cognitive thinking, affecting one’s ability to carry out daily activities. Aging, bad dietary habits, family history, as well as altered gut microbiota composition may play a role in the pathogenesis of AD. Although the association between the imbalance of gut microbiota and AD is still difficult to determine, it has been suggested that dysbiosis can lead to the increased secretion of lipopolysaccharides and amyloid, which may impair the permeability of the intestine and the blood-brain barrier. Moreover, it can progress the process of neuroinflammation, amyloid-beta formation, and ultimately neuronal death. Microbiota-targeted interventions such as personalized diet, probiotics, or fecal microbiota transplantation (FMT) might represent a potential therapeutic option for AD. This review article discusses the procedure of FMT and its possible side effects on the recipient’s body. In addition, we review the role of FMT in the context of its application in various nervous system-related disorders (AD, Parkinson’s disease, multiple sclerosis).
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Affiliation(s)
- Varsha Nandwana
- Medicine, Lady Hardinge Medical College and Associated Hospitals, New Delhi, IND
| | - Shibajee Debbarma
- Community Medicine, Lady Hardinge Medical College and Associated Hospitals, New Delhi, IND
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35
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Roviello G, Iannone LF, Bersanelli M, Mini E, Catalano M. The gut microbiome and efficacy of cancer immunotherapy. Pharmacol Ther 2021; 231:107973. [PMID: 34453999 DOI: 10.1016/j.pharmthera.2021.107973] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/07/2021] [Accepted: 07/27/2021] [Indexed: 12/14/2022]
Abstract
Cancer treatment has been deeply changed by immunotherapy, achieving unprecedented improvement in overall and progression-free survival in several advanced and metastatic cancers. Currently, immune checkpoint inhibitor (ICI) antibodies against cytotoxic T-lymphocyte antigen (CTLA-4) and programmed death/ligand 1 (PD-1/PD-L1) are being tested and approved for different tumors, ranging from melanoma to lung carcinoma. However, only a subgroup of patients can reach treatment benefits and long-term responses, and reliable biomarkers that can accurately predict clinical responses to immunotherapy are still unidentified. In the last decade, accumulating evidence seems to suggest the gut microbiota as one of the modulators that can alter the efficacy and toxicity of immunotherapy drugs (as well as chemotherapeutics), mainly acting through the local and systemic immune system. Herein, we reviewed the highly dynamic and complex microbiome-immune system interface, its bidirectional relationship with cancer immunotherapies, and explored the future possibilities and risks in manipulating the gut microbiome.
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Affiliation(s)
- Giandomenico Roviello
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy.
| | | | - Melissa Bersanelli
- Medical Oncology, University Hospital of Parma and Medicine and Surgery Department, University of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Enrico Mini
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy
| | - Martina Catalano
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy
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Mohapatra RK, Dhama K, Mishra S, Sarangi AK, Kandi V, Tiwari R, Pintilie L. The microbiota-related coinfections in COVID-19 patients: a real challenge. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2021; 10:47. [PMID: 34458380 PMCID: PMC8380112 DOI: 10.1186/s43088-021-00134-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 07/29/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of ongoing global pandemic of coronavirus disease 2019 (COVID-19), has infected millions of people around the world, especially the elderly and immunocompromised individuals. The infection transmission rate is considered more rapid than other deadly pandemics and severe epidemics encountered earlier, such as Ebola, Zika, Influenza, Marburg, SARS, and MERS. The public health situation therefore is really at a challenging crossroads. MAIN BODY The internal and external and resident microbiota community is crucial in human health and is essential for immune responses. This community tends to be altered due to pathogenic infections which would lead to severity of the disease as it progresses. Few of these resident microflora become negatively active during infectious diseases leading to coinfection, especially the opportunistic pathogens. Once such a condition sets in, it is difficult to diagnose, treat, and manage COVID-19 in a patient. CONCLUSION This review highlights the various reported possible coinfections that arise in COVID-19 patients vis-à-vis other serious pathological conditions. The local immunity in lungs, nasal passages, oral cavity, and salivary glands are involved with different aspects of COVID-19 transmission and pathology. Also, the role of adaptive immune system is discussed at the site of infection to control the infection along with the proinflammatory cytokine therapy.
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Affiliation(s)
- Ranjan K. Mohapatra
- Department of Chemistry, Government College of Engineering, Keonjhar, Odisha 758002 India
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh 243122 India
| | - Snehasish Mishra
- School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024 India
| | - Ashish K. Sarangi
- Department of Chemistry, School of Applied Sciences, Centurion University of Technology and Management, Odisha, India
| | - Venkataramana Kandi
- Department of Microbiology, Prathima Institute of Medical Sciences, Karimnagar, Telangana India
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan (DUVASU), Mathura, 281001 India
| | - Lucia Pintilie
- Department of Synthesis of Bioactive Substances and Pharmaceutical Technologies, National Institute for Chemical and Pharmaceutical Research and Development, Bucharest, Romania
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Faraj J, Takanti V, Tavakoli HR. The Gut-Brain Axis: Literature Overview and Psychiatric Applications. Fed Pract 2021; 38:356-362. [PMID: 34733087 PMCID: PMC8560095 DOI: 10.12788/fp.0159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IMPORTANCE Literature exploring the relationship between the intestinal microbiome and its effects on general health and well-being has grown significantly in recent years, and our knowledge of this subject continues to grow. Mounting evidence indicates that the intestinal microbiome is a potential target for therapeutic intervention in psychiatric illness and in neurodegenerative disorders such as Alzheimer disease. It is reasonable to consider modulating not just a patient's neurochemistry, behavior, or cognitive habits, but also their intestinal microbiome in an effort to improve psychiatric symptoms. OBSERVATIONS In this review paper, we show that intestinal microbiota possess the ability to directly influence both physical and mental well-being; therefore, should be included in future discussions regarding psychiatric treatment. CONCLUSIONS Clinicians are encouraged to consider patients' gut health when evaluating and treating psychiatric conditions, such as anxiety and depression. Optimization and diversification of gut flora through the use of psychobiotics-probiotics that confer mental health benefits-may soon become standard practice in conjunction with traditional psychiatric treatment modalities such as pharmacotherapy and psychotherapy.
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Affiliation(s)
- Janine Faraj
- is a General Medical Officer at Naval Surface Forces Atlantic, Medical Readiness Division, Norfolk, Virginia. is a Resident Physician in the Department of Anesthesiology at Rush University Hospital in Chicago, Illinois. is the head of Psychiatry Consultation-Liaison Services at the Naval Medical Center, Portsmouth, Virginia
| | - Varun Takanti
- is a General Medical Officer at Naval Surface Forces Atlantic, Medical Readiness Division, Norfolk, Virginia. is a Resident Physician in the Department of Anesthesiology at Rush University Hospital in Chicago, Illinois. is the head of Psychiatry Consultation-Liaison Services at the Naval Medical Center, Portsmouth, Virginia
| | - Hamid R Tavakoli
- is a General Medical Officer at Naval Surface Forces Atlantic, Medical Readiness Division, Norfolk, Virginia. is a Resident Physician in the Department of Anesthesiology at Rush University Hospital in Chicago, Illinois. is the head of Psychiatry Consultation-Liaison Services at the Naval Medical Center, Portsmouth, Virginia
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Amjad W, Haider R, Malik A, Qureshi W. Insights into the management of anorectal disease in the coronavirus 2019 disease era. Therap Adv Gastroenterol 2021; 14:17562848211028117. [PMID: 34290826 PMCID: PMC8274100 DOI: 10.1177/17562848211028117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [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: 06/08/2021] [Indexed: 02/04/2023] Open
Abstract
Coronavirus 2019 disease (COVID-19) has created major impacts on public health. The virus has plagued a large population requiring hospitalization and resource utilization. Knowledge about the COVID-19 virus continues to grow. It can commonly present with gastrointestinal symptoms; initially, this was considered an atypical presentation, which led to delays in care. The pandemic has posed serious threats to the care of anorectal diseases. Urgent surgeries have been delayed, and the care of cancer patients and cancer screenings disrupted. This had added to patient discomfort and the adverse outcomes on healthcare will continue into the future. The better availability of personal protective equipment to providers and standard checklist protocols in operating rooms can help minimize healthcare-related spread of the virus. Telehealth, outpatient procedures, and biochemical tumor marker tests can help with mitigation of anorectal-disease-related problems. There is limited literature about the clinical management of anorectal diseases during the pandemic. We performed a detailed literature review to guide clinicians around management options for anorectal disease patients. We also highlighted the health challenges seen during the pandemic.
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Affiliation(s)
- Waseem Amjad
- Internal Medicine, Albany Medical Center, Albany, NY, USA
| | - Rabbia Haider
- Internal Medicine, Nishter Medical University, Multan, Punjab, Pakistan
| | - Adnan Malik
- Internal Medicine, Loyola University School of Medicine, Chicago, IL, USA
| | - Waqas Qureshi
- Section of Cardiology in Division of Internal Medicine, University of Massachusetts School of Medicine, Worcester, MA 01655, USA
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Subtotal colectomy for refractory ulcerative colitis with COVID-19 infection; a first case report in Japan. Clin J Gastroenterol 2021; 14:1437-1442. [PMID: 34213760 PMCID: PMC8250545 DOI: 10.1007/s12328-021-01472-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 06/23/2021] [Indexed: 10/29/2022]
Abstract
We report a 60-year-old male who was transferred to our hospital for the operation because of refractory ulcerative colitis (UC). He was diagnosed to be infected with COVID-19 for SARS-CoV-2 PCR test positive at the time of transfer. We determined emergency operation because his general condition was poor such as malnutrition and ADL decline due to exacerbation of UC and air embolization by central venous catheter removal. He underwent subtotal colectomy with a sigmoid mucous fistula and ileostomy. He was well postoperatively. This is a first case report in Japan who underwent an operation for UC with COVID-19 infection.
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Zhang J, Garrett S, Sun J. Gastrointestinal symptoms, pathophysiology, and treatment in COVID-19. Genes Dis 2021; 8:385-400. [PMID: 33521210 PMCID: PMC7836435 DOI: 10.1016/j.gendis.2020.08.013] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/18/2020] [Accepted: 08/28/2020] [Indexed: 01/08/2023] Open
Abstract
The novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged and is responsible for the Coronavirus Disease 2019 global pandemic. Coronaviruses, including SARS-CoV-2, are strongly associated with respiratory symptoms during infection, but gastrointestinal symptoms, such as diarrhea, vomiting, nausea, and abdominal pain, have been identified in subsets of COVID-19 patients. This article focuses on gastrointestinal symptoms and pathophysiology in COVID-19 disease. Evidence suggests that the gastrointestinal tract could be a viral target for SARS-CoV-2 infection. Not only is the SARS-CoV-2 receptor ACE2 highly expressed in the GI tract and is associated with digestive symptoms, but bleeding and inflammation are observed in the intestine of COVID-19 patients. We further systemically summarize the correlation between COVID-19 disease, gastrointestinal symptoms and intestinal microbiota. The potential oral-fecal transmission of COVID-19 was supported by viral RNA and live virus detection in the feces of COVID-19 patients. Additionally, the viral balance in the GI tract could be disordered during SARS-CoV-2 infection which could further impact the homeostasis of the gut microbial flora. Finally, we discuss the clinical and ongoing trials of treatments/therapies, including antiviral drugs, plasma transfusion and immunoglobulins, and diet supplementations for COVID-19. By reviewing the pathogenesis of SARS-CoV-2 virus, and understanding the correlation among COVID-19, inflammation, intestinal microbiota, and lung microbiota, we provide perspective in prevention and control, as well as diagnosis and treatment of the COVID-19 disease.
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Affiliation(s)
- Jilei Zhang
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Shari Garrett
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
- Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Jun Sun
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
- UIC Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA
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Hoffmann-Vold AM, Fretheim HH, Sarna VK, Barua I, Carstens MN, Distler O, Khanna D, Volkmann ER, Midtvedt Ø, Didriksen H, Dhainaut A, Halse AK, Bakland G, Pesonen M, Olsen I, Molberg Ø. Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial. BMJ Open 2021; 11:e048541. [PMID: 34168032 PMCID: PMC8231046 DOI: 10.1136/bmjopen-2020-048541] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 06/01/2021] [Indexed: 01/22/2023] Open
Abstract
INTRODUCTION In the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture 'Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)'. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc. METHODS AND ANALYSES We aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating). ETHICS AND DISSEMINATION This protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published. TRIAL REGISTRATION NUMBER NCT04300426; Pre-results. PROTOCOL VERSION V.3.1.
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Affiliation(s)
- Anna-Maria Hoffmann-Vold
- Department of Rheumatology, Oslo University Hospital, Oslo, Norway
- Faculty of medicine, University of Oslo, Oslo, Norway
| | - Håvard H Fretheim
- Department of Rheumatology, Oslo University Hospital, Oslo, Norway
- Faculty of medicine, University of Oslo, Oslo, Norway
| | - Vikas K Sarna
- Department of gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Imon Barua
- Department of Rheumatology, Oslo University Hospital, Oslo, Norway
- Faculty of medicine, University of Oslo, Oslo, Norway
| | | | - Oliver Distler
- Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
| | - Dinesh Khanna
- Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Elizabeth R Volkmann
- Division of Rheumatology, David Geffen School of Medicine, Los Angeles, California, USA
| | - Øyvind Midtvedt
- Department of Rheumatology, Oslo University Hospital, Oslo, Norway
| | - Henriette Didriksen
- Department of Rheumatology, Oslo University Hospital, Oslo, Norway
- Faculty of medicine, University of Oslo, Oslo, Norway
| | - Alvilde Dhainaut
- Department of Rheumatology, St Olavs Hospital Universitetssykehuset i Trondheim, Trondheim, Norway
| | | | - Gunnstein Bakland
- Department of Rheumatology, University Hospital of North Norway, Tromso, Troms, Norway
| | - Maiju Pesonen
- Oslo Centre for Biostatistics & Epidemiology, Oslo University Hospital, Oslo, Norway
| | - Inge Olsen
- Oslo Centre for Biostatistics & Epidemiology, Oslo University Hospital, Oslo, Norway
| | - Øyvind Molberg
- Department of Rheumatology, Oslo University Hospital, Oslo, Norway
- Faculty of medicine, University of Oslo, Oslo, Norway
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Battaglini D, Robba C, Fedele A, Trancǎ S, Sukkar SG, Di Pilato V, Bassetti M, Giacobbe DR, Vena A, Patroniti N, Ball L, Brunetti I, Torres Martí A, Rocco PRM, Pelosi P. The Role of Dysbiosis in Critically Ill Patients With COVID-19 and Acute Respiratory Distress Syndrome. Front Med (Lausanne) 2021; 8:671714. [PMID: 34150807 PMCID: PMC8211890 DOI: 10.3389/fmed.2021.671714] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 05/12/2021] [Indexed: 12/12/2022] Open
Abstract
In late December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) quickly spread worldwide, and the syndrome it causes, coronavirus disease 2019 (COVID-19), has reached pandemic proportions. Around 30% of patients with COVID-19 experience severe respiratory distress and are admitted to the intensive care unit for comprehensive critical care. Patients with COVID-19 often present an enhanced immune response with a hyperinflammatory state characterized by a "cytokine storm," which may reflect changes in the microbiota composition. Moreover, the evolution to acute respiratory distress syndrome (ARDS) may increase the severity of COVID-19 and related dysbiosis. During critical illness, the multitude of therapies administered, including antibiotics, sedatives, analgesics, body position, invasive mechanical ventilation, and nutritional support, may enhance the inflammatory response and alter the balance of patients' microbiota. This status of dysbiosis may lead to hyper vulnerability in patients and an inappropriate response to critical circumstances. In this context, the aim of our narrative review is to provide an overview of possible interaction between patients' microbiota dysbiosis and clinical status of severe COVID-19 with ARDS, taking into consideration the characteristic hyperinflammatory state of this condition, respiratory distress, and provide an overview on possible nutritional strategies for critically ill patients with COVID-19-ARDS.
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Affiliation(s)
- Denise Battaglini
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Chiara Robba
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
| | - Andrea Fedele
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
| | - Sebastian Trancǎ
- Department of Anesthesia and Intensive Care II, Clinical Emergency County Hospital of Cluj, Iuliu Hatieganu, University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Anaesthesia and Intensive Care 1, Clinical Emergency County Hospital Cluj-Napoca, Cluj-Napoca, Romania
| | - Samir Giuseppe Sukkar
- Dietetics and Clinical Nutrition Unit, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
| | - Vincenzo Di Pilato
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
| | - Matteo Bassetti
- Clinica Malattie Infettive, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Dipartimento di Scienze della Salute (DISSAL), Università degli Studi di Genova, Genova, Italy
| | - Daniele Roberto Giacobbe
- Clinica Malattie Infettive, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Dipartimento di Scienze della Salute (DISSAL), Università degli Studi di Genova, Genova, Italy
| | - Antonio Vena
- Clinica Malattie Infettive, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
| | - Nicolò Patroniti
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
| | - Lorenzo Ball
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
| | - Iole Brunetti
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
| | - Antoni Torres Martí
- Department of Medicine, University of Barcelona, Barcelona, Spain
- Division of Animal Experimentation, Department of Pulmonology, Hospital Clinic, Barcelona, Spain
- Centro de Investigacion en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d'investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Patricia Rieken Macedo Rocco
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- COVID-19-Network, Ministry of Science, Technology, Innovation and Communication, Brasilia, Brazil
| | - Paolo Pelosi
- Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), Università degli Studi di Genova, Genova, Italy
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Imwattana K, Knight DR, Riley TV. Can sequencing improve the diagnosis and management of Clostridioides difficile infection? Expert Rev Mol Diagn 2021; 21:429-431. [PMID: 33843381 DOI: 10.1080/14737159.2021.1915774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Korakrit Imwattana
- School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.,Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Daniel R Knight
- School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.,Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia
| | - Thomas V Riley
- School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.,Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia.,PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Australia
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Chen J, Zaman A, Ramakrishna B, Olesen SW. Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank. Front Cell Infect Microbiol 2021; 11:622949. [PMID: 33937092 PMCID: PMC8082449 DOI: 10.3389/fcimb.2021.622949] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 03/22/2021] [Indexed: 12/15/2022] Open
Abstract
Objectives Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of microbiota-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of expanding access to FMT material while simultaneously improving its safety, quality, and convenience. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks. Methods To help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year. Results In 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank's partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month. Conclusions Further knowledge sharing should help inform refinements of stool banking guidelines and best practices.
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45
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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: 0] [Impact Index Per Article: 0] [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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Abstract
Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.
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Coryell MP, Iakiviak M, Pereira N, Murugkar PP, Rippe J, Williams DB, Heald-Sargent T, Sanchez-Pinto LN, Chavez J, Hastie JL, Sava RL, Lien CZ, Wang TT, Muller WJ, Fischbach MA, Carlson PE. A method for detection of SARS-CoV-2 RNA in healthy human stool: a validation study. LANCET MICROBE 2021; 2:e259-e266. [PMID: 33821247 PMCID: PMC8012028 DOI: 10.1016/s2666-5247(21)00059-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background Faecal shedding of SARS-CoV-2 has raised concerns about transmission through faecal microbiota transplantation procedures. Validation parameters of authorised tests for SARS-CoV-2 RNA detection in respiratory samples are described in product labelling, whereas the published methods for SARS-CoV-2 detection from faecal samples have not permitted a robust description of the assay parameters. We aimed to develop and validate a test specifically for detection of SARS-CoV-2 in human stool. Methods In this validation study, we evaluated performance characteristics of a reverse transcriptase real-time PCR (RT-rtPCR) test for detection of SARS-CoV-2 in human stool specimens by spiking stool with inactivated SARS-CoV-2 material. A modified version of the US Centers for Disease Control and Prevention RT-rtPCR SARS-CoV-2 test was used for detection of viral RNA. Analytical sensitivity was evaluated in freshly spiked stool by testing two-fold dilutions in replicates of 20. Masked samples were tested by a second laboratory to evaluate interlaboratory reproducibility. Short-term (7-day) stability of viral RNA in stool samples was assessed with four different stool storage buffers (phosphate-buffered saline, Cary-Blair medium, Stool Transport and Recovery [STAR] buffer, and DNA/RNA Shield) kept at −80°C, 4°C, and ambient temperature (approximately 21°C). We also tested clinical stool and anal swab specimens from patients who were SARS-CoV-2 positive by nasopharyngeal testing. Findings The lower limit of detection of the assay was found to be 3000 viral RNA copies per g of original stool sample, with 100% detection across 20 replicates assessed at this concentration. Analytical sensitivity was diminished by approximately two times after a single freeze-thaw cycle at −80°C. At 100 times the limit of detection, spiked samples were generally stable in all four stool storage buffers tested for up to 7 days, with maximum changes in mean threshold cycle values observed at −80°C storage in Cary-Blair medium (from 29·4 [SD 0·27] at baseline to 30·8 [0·17] at day 7; p<0·0001), at 4°C storage in DNA/RNA Shield (from 28·5 [0·15] to 29·8 [0·09]; p=0·0019), and at ambient temperature in STAR buffer (from 30·4 [0·24] to 32·4 [0·62]; p=0·0083). 30 contrived SARS-CoV-2 samples were tested by a second laboratory and were correctly identified as positive or negative in at least one of two rounds of testing. Additionally, SARS-CoV-2 RNA was detected using this assay in the stool and anal swab specimens of 11 of 23 individuals known to be positive for SARS-CoV-2. Interpretation This is a sensitive and reproducible assay for detection of SARS-CoV-2 RNA in human stool, with potential uses in faecal microbiota transplantation donor screening, sewage monitoring, and further research into the effects of faecal shedding on the epidemiology of the COVID-19 pandemic. Funding National Institute of Allergy and Infectious Diseases, US National Institutes of Health; Center for Biologics Evaluation and Research, US Food and Drug Administration.
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Affiliation(s)
- Michael P Coryell
- Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Mikhail Iakiviak
- Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA
| | - Nicole Pereira
- Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA
| | - Pallavi P Murugkar
- Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA
| | - Jason Rippe
- Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital, Chicago, IL, USA
| | - David B Williams
- Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital, Chicago, IL, USA
| | - Taylor Heald-Sargent
- Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital, Chicago, IL, USA.,Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - L Nelson Sanchez-Pinto
- Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital, Chicago, IL, USA.,Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jairo Chavez
- Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital, Chicago, IL, USA.,Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jessica L Hastie
- Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Rosa L Sava
- Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Christopher Z Lien
- Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Tony T Wang
- Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - William J Muller
- Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital, Chicago, IL, USA.,Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Michael A Fischbach
- Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA
| | - Paul E Carlson
- Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
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Kazemian N, Kao D, Pakpour S. Fecal Microbiota Transplantation during and Post-COVID-19 Pandemic. Int J Mol Sci 2021; 22:3004. [PMID: 33809421 PMCID: PMC7998826 DOI: 10.3390/ijms22063004] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/09/2021] [Accepted: 03/11/2021] [Indexed: 01/07/2023] Open
Abstract
COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.
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Affiliation(s)
- Negin Kazemian
- School of Engineering, University of British Columbia, Kelowna, BC V1V 1V7, Canada;
| | - Dina Kao
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada;
| | - Sepideh Pakpour
- School of Engineering, University of British Columbia, Kelowna, BC V1V 1V7, Canada;
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Skladany L, Koller T, Adamcova Selcanova S, Vnencakova J, Jancekova D, Durajova V, Laffers L, Svac J, Janickova K, Palkovič M, Kohout P, Golubnitschaja O. Challenging management of severe chronic disorders in acute pandemic situation: Chronic liver disease under COVID-19 pandemic as the proof-of-principle model to orchestrate the measures in 3PM context. EPMA J 2021; 12:1-14. [PMID: 33680218 PMCID: PMC7926196 DOI: 10.1007/s13167-021-00231-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 01/11/2021] [Indexed: 02/06/2023]
Abstract
Chronic liver disease management is a comprehensive approach requiring multi-professional expertise and well-orchestrated healthcare measures thoroughly organized by responsible medical units. Contextually, the corresponding multi-faceted chain of healthcare events is likely to be severely disturbed or even temporarily broken under the force majeure conditions such as global pandemics. Consequently, the chronic liver disease is highly representative for the management of any severe chronic disorder under lasting pandemics with unprecedented numbers of acutely diseased persons who, together with the chronically sick patient cohorts, have to be treated using the given capacity of healthcare systems with their limited resources. Current study aimed at exploring potentially negative impacts of the SARS CoV-2 outbreak on the quality of the advanced chronic liver disease (ACLD) management considering two well-classified parameters, namely, (1) the continuity of the patient registrations and (2) the level of mortality rates, comparing pre-COVID-19 statistics with these under the current pandemic in Slovak Republic. Altogether 1091 registrations to cirrhosis registry (with 60.8% versus 39.2% males to females ratio) were included with a median age of 57 years for patients under consideration. Already within the very first 3 months of the pandemic outbreak in Slovakia (lockdown declared from March 16, 2020, until May 20, 2020), the continuity of the patient registrations has been broken followed by significantly increased ACLD-related death rates. During this period of time, the total number of new registrations decreased by about 60% (15 registrations in 2020 versus 38 in 2018 and 38 in 2019). Corresponding mortality increased by about 52% (23 deaths in 2020 versus 10 in 2018 and 12 in 2019). Based on these results and in line with the framework of 3PM guidelines, the pandemic priority pathways (PPP) are strongly recommended for maintaining tertiary care uninterrupted. For the evidence-based implementation of PPP, creation of predictive algorithms and individualized care strategy tailored to the patient is essential. Resulting classification of measures is summarized as follows:
The Green PPP Line is reserved for prioritized (urgent and comprehensive) treatment of patients at highest risk to die from ACLD (tertiary care) as compared to the risk from possible COVID-19 infection. The Orange PPP Line considers patients at middle risk of adverse outcomes from ACLD with re-addressing them to the secondary care. As further deterioration of ACLD is still probable, pro-active management is ascertained with tertiary center serving as the 24/7 telemedicine consultation hub for a secondary facility (on a physician-physician level). The Red PPP Line is related to the patients at low risk to die from ACLD, re-addressing them to the primary care. Since patients with stable chronic liver diseases without advanced fibrosis are at trivial inherent risk, they should be kept out of the healthcare setting as far as possible by the telemedical (patient-nurse or patient- physician) measurements. The assigned priority has to be monitored and re-evaluated individually—in intervals based on the baseline prognostic score such as MELD. The approach is conform with principles of predictive, preventive and personalized medicine (PPPM / 3PM) and demonstrates a potential of great clinical utility for an optimal management of any severe chronic disorder (cardiovascular, neurological and cancer) under lasting pandemics.
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Affiliation(s)
- Lubomir Skladany
- HEGITO (Div. Hepatology, Gastroenterology, and Liver Transplantation) of the Department of Internal Medicine II, Faculty of Medicine, Slovak Medical University, F. D. Roosevelt Teaching Hospital, Banska Bystrica, Slovakia
| | - Tomas Koller
- 5th Department of Internal Medicine, Comenius University Faculty of Medicine, University Hospital Bratislava Ruzinov, Bratislava, Slovakia
| | - Svetlana Adamcova Selcanova
- HEGITO (Div. Hepatology, Gastroenterology, and Liver Transplantation) of the Department of Internal Medicine II, Faculty of Medicine, Slovak Medical University, F. D. Roosevelt Teaching Hospital, Banska Bystrica, Slovakia
| | - Janka Vnencakova
- HEGITO (Div. Hepatology, Gastroenterology, and Liver Transplantation) of the Department of Internal Medicine II, Faculty of Medicine, Slovak Medical University, F. D. Roosevelt Teaching Hospital, Banska Bystrica, Slovakia
| | - Daniela Jancekova
- HEGITO (Div. Hepatology, Gastroenterology, and Liver Transplantation) of the Department of Internal Medicine II, Faculty of Medicine, Slovak Medical University, F. D. Roosevelt Teaching Hospital, Banska Bystrica, Slovakia
| | - Viktoria Durajova
- Department of Science and Research, F.D. Roosevelt Teaching Hospital, Banska Bystrica, Slovakia
| | - Lukas Laffers
- Department of Mathematics, Faculty of Natural Sciences, Matej Bel University, Banska Bystrica, Slovakia
| | - Juraj Svac
- HEGITO (Div. Hepatology, Gastroenterology, and Liver Transplantation) of the Department of Internal Medicine II, Faculty of Medicine, Slovak Medical University, F. D. Roosevelt Teaching Hospital, Banska Bystrica, Slovakia
| | - Katarina Janickova
- Central Evidence Department, Health Care Surveillance Authority (HCSA), Bratislava, Slovakia
| | - Michal Palkovič
- Forensic Medicine and Pathological Anatomy Department, Health Care Surveillance Authority (HCSA), Bratislava, Slovakia
| | - Pavel Kohout
- Department of Internal Medicine, 3Rd Medical Faculty Charles University, Thomayer Hospital Prague, Prague, Czech Republic
| | - Olga Golubnitschaja
- Predictive, Preventive Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.,3PM Research Unit, Department of Radiation Oncology, University Hospital, Medical Faculty, Rheinische Friedrich-Wilhelms-Universität Bonn, 53107 Bonn, Germany
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Ianiro G, Mullish BH, Hvas CL, Segal JP, Kuijper EJ, Costello SP, Kelly CR, Allegretti JR, Fischer M, Iqbal TH, Satokari R, Kao D, van Prehn J, Ng SC, Bibbò S, Baunwall SMD, Quraishi MN, Sokol H, Zhang F, Keller J, Masucci L, Quaranta G, Kassam Z, Sanguinetti M, Tilg H, Gasbarrini A, Cammarota G. SARS-CoV-2 vaccines and donor recruitment for FMT. Lancet Gastroenterol Hepatol 2021; 6:264-266. [PMID: 33571456 PMCID: PMC7906701 DOI: 10.1016/s2468-1253(21)00032-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 01/24/2021] [Accepted: 01/24/2021] [Indexed: 12/24/2022]
Affiliation(s)
- Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario "A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Benjamin H Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Jonathan P Segal
- Department of Gastroenterology, Hillingdon Hospital, Uxbridge, UK
| | - Ed J Kuijper
- Department of Medical Microbiology, Leiden University Medical Centre, Leiden, Netherlands; Netherlands Donor Feces Bank, Leiden University Medical Centre, Leiden, Netherlands
| | - Samuel P Costello
- Department of Gastroenterology, The Queen Elizabeth Hospital, University of Adelaide, Woodville, SA, Australia
| | - Colleen R Kelly
- Division of Gastroenterology, Alpert Medical School of Brown University, Providence, RI, USA
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Monika Fischer
- Department of Medicine, Indiana University, Indianapolis, IN, USA
| | - Tariq H Iqbal
- University of Birmingham Microbiome Treatment Centre, University of Birmingham, Birmingham, UK; Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Reetta Satokari
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Dina Kao
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Joffrey van Prehn
- Department of Medical Microbiology, Leiden University Medical Centre, Leiden, Netherlands; Netherlands Donor Feces Bank, Leiden University Medical Centre, Leiden, Netherlands
| | - Siew C Ng
- Center for Gut Microbiota Research, Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Stefano Bibbò
- Digestive Disease Center, Fondazione Policlinico Universitario "A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Mohammed N Quraishi
- University of Birmingham Microbiome Treatment Centre, University of Birmingham, Birmingham, UK; Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Harry Sokol
- Service de Gastroenterologie, Hôpital Saint Antoine, Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, Paris, France; French Group of Fecal Microbiota Transplantation, Paris, France; INRA, UMR1319 Micalis, AgroParisTech, Jouy-en-Josas, France
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Josbert Keller
- Netherlands Donor Feces Bank, Leiden University Medical Centre, Leiden, Netherlands; Department of Gastroenterology, Leiden University Medical Centre, Leiden, Netherlands; Department of Gastroenterology, Haaglanden Medical Center, The Hague, Netherlands
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario "A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Quaranta
- Microbiology Unit, Fondazione Policlinico Universitario "A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Zain Kassam
- Finch Therapeutics Group, Somerville, MA, USA
| | - Maurizio Sanguinetti
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Innsbruck Medical University, Innsbruck, Austria; Microbiology Unit, Fondazione Policlinico Universitario "A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Innsbruck Medical University, Innsbruck, Austria; Microbiology Unit, Fondazione Policlinico Universitario "A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario "A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario "A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
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