1
|
Hirsch W, Fischer M, Khoruts A, Allegretti JR, Kelly CR, Vaughn B. Risk Factors for Antibiotic Exposure Post-Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Prospective Multicenter Observational Study. Open Forum Infect Dis 2025; 12:ofaf130. [PMID: 40103733 PMCID: PMC11913780 DOI: 10.1093/ofid/ofaf130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 03/05/2025] [Indexed: 03/20/2025] Open
Abstract
Background Recurrent Clostridioides difficile infection (CDI) is primarily driven by antibiotic-induced disruption of the indigenous intestinal microbiota. Restoration of microbiota through fecal microbiota transplantation (FMT) is effective in preventing subsequent CDI, although this effect is attenuated with additional antibiotic exposure. The aim of this study was to identify the risk factors for recurrent antibiotic administration after FMT. Methods This is a prospective cohort of patients who were administered FMT for recurrent CDI from 1 July 2019 through 23 November 2023 across 6 institutions in the United States. Providers collected de-identified data at the time of FMT administration and in the months post-FMT administration. Results The analysis included 448 patients. Risk factors for non-CDI antibiotic administration within 2 months of FMT included immunocompromised status (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.1-4.4]; P = .02), >3 non-CDI antibiotic courses pre-FMT (OR, 3.1 [95% CI, 1.4-6.8]; P = .006), and prior hospitalization for CDI (OR, 2.0 [95% CI, 1.1-3.8]; P = .02). The most common indications for non-CDI antibiotic administration post-FMT were urinary tract infections, respiratory infections, and procedure prophylaxis. Conclusions Non-CDI antibiotic exposure significantly increases the risk of CDI recurrence post-FMT. Risk factors for non-CDI antibiotic administration within 2 months of FMT include immunocompromised status, multiple prior non-CDI antibiotics, and prior hospitalization for CDI. These individuals may benefit from additional or modified recurrent CDI prevention strategies.
Collapse
Affiliation(s)
- William Hirsch
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Monika Fischer
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Alexander Khoruts
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
- Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA
- BioTechnology Institute, University of Minnesota, St Paul, Minnesota, USA
| | | | - Colleen R Kelly
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Byron Vaughn
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| |
Collapse
|
2
|
Ullah H, Arbab S, Chang C, Bibi S, Muhammad N, Rehman SU, Suleman, Ullah I, Hassan IU, Tian Y, Li K. Gut microbiota therapy in gastrointestinal diseases. Front Cell Dev Biol 2025; 13:1514636. [PMID: 40078367 PMCID: PMC11897527 DOI: 10.3389/fcell.2025.1514636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.
Collapse
Affiliation(s)
- Hanif Ullah
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Safia Arbab
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Chengting Chang
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Saira Bibi
- Department of Zoology Hazara University Manshera, Dhodial, Pakistan
| | - Nehaz Muhammad
- Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, Hebei Collaborative Innovation Center for Eco-Environment, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, China
| | - Sajid Ur Rehman
- School of Public Health and Emergency Management, School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Suleman
- Department of Zoology, Government Post Graduate Collage, Swabi, Pakistan
- Higher Education Department, Civil Secretariat Peshawar, Peshawar, Pakistan
| | - Irfan Ullah
- Department of Biotechnology and Genetics Engineering, Hazara University, Manshera, Pakistan
| | - Inam Ul Hassan
- Department of Microbiology, Hazara University Manshera, Manshera, Pakistan
| | - Yali Tian
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Ka Li
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| |
Collapse
|
3
|
Rondanelli M, Borromeo S, Cavioni A, Gasparri C, Gattone I, Genovese E, Lazzarotti A, Minonne L, Moroni A, Patelli Z, Razza C, Sivieri C, Valentini EM, Barrile GC. Therapeutic Strategies to Modulate Gut Microbial Health: Approaches for Chronic Metabolic Disorder Management. Metabolites 2025; 15:127. [PMID: 39997751 PMCID: PMC11857149 DOI: 10.3390/metabo15020127] [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: 12/02/2024] [Revised: 01/17/2025] [Accepted: 01/28/2025] [Indexed: 02/26/2025] Open
Abstract
Numerous recent studies have suggested that the composition of the intestinal microbiota can trigger metabolic disorders, such as diabetes, prediabetes, obesity, metabolic syndrome, sarcopenia, dyslipidemia, hyperhomocysteinemia, and non-alcoholic fatty liver disease. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and metabolic disorders, as well as the role of probiotics in the modulation of the intestinal microbiota. The aim of this review was to summarize the reviews and individual articles on the state of the art regarding ideal therapy with probiotics and prebiotics in order to obtain the reversion of dysbiosis (alteration in microbiota) to eubiosis during metabolic diseases, such as diabetes, prediabetes, obesity, hyperhomocysteinemia, dyslipidemia, sarcopenia, and non-alcoholic fatty liver diseases. This review includes 245 eligible studies. In conclusion, a condition of dysbiosis, or in general, alteration of the intestinal microbiota, could be implicated in the development of metabolic disorders through different mechanisms, mainly linked to the release of pro-inflammatory factors. Several studies have already demonstrated the potential of using probiotics and prebiotics in the treatment of this condition, detecting significant improvements in the specific symptoms of metabolic diseases. These findings reinforce the hypothesis that a condition of dysbiosis can lead to a generalized inflammatory picture with negative consequences on different organs and systems. Moreover, this review confirms that the beneficial effects of probiotics on metabolic diseases are promising, but more research is needed to determine the optimal probiotic strains, doses, and administration forms for specific metabolic conditions.
Collapse
Affiliation(s)
- Mariangela Rondanelli
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy;
| | - Sara Borromeo
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessandro Cavioni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Ilaria Gattone
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Elisa Genovese
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessandro Lazzarotti
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Leonardo Minonne
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessia Moroni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Zaira Patelli
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Claudia Razza
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Claudia Sivieri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Eugenio Marzio Valentini
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Gaetan Claude Barrile
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| |
Collapse
|
4
|
Aran KR, Porel P, Hunjan G, Singh S, Gupta GD, Rohit. Postbiotics as a therapeutic tool in Alzheimer's disease: Insights into molecular pathways and neuroprotective effects. Ageing Res Rev 2025; 106:102685. [PMID: 39922231 DOI: 10.1016/j.arr.2025.102685] [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: 12/24/2024] [Revised: 02/05/2025] [Accepted: 02/05/2025] [Indexed: 02/10/2025]
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by oxidative stress, neuroinflammation, mitochondrial dysfunction, neurotransmitter imbalance, tau hyperphosphorylation, and amyloid beta (Aβ) accumulation in brain regions. The gut microbiota (GM) has a major impact on brain function due to its bidirectional interaction with the gut through the gut-brain axis. The gut dysbiosis has been associated with neurological disorders, emphasizing the importance of gut homeostasis in maintaining appropriate brain function. The changes in the composition of microbiomes influence neuroinflammation and Aβ accumulation by releasing pro-inflammatory cytokines, decreasing gut and blood-brain barrier (BBB) integrity, and microglial activation in the brain. Postbiotics, are bioactive compounds produced after fermentation, have been shown to provide several health benefits, particularly in terms of neuroinflammation and cognitive alterations associated with AD. Several research studies on animal models and human have successfully proven the effects of postbiotics on enhancing cognition and memory in experimental animals. This article explores the protective effects of postbiotics on cellular mechanisms responsible for AD pathogenesis and studies highlighting the influence of postbiotics as a total combination and specific compounds, including short-chain fatty acids (SCFAs). In addition, postbiotics act as a promising option for future research to deal with AD's progressive nature and improve an individual's life quality using microbiota modulation.
Collapse
Affiliation(s)
- Khadga Raj Aran
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga-142001, Punjab, India.
| | - Pratyush Porel
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga-142001, Punjab, India
| | - Garry Hunjan
- Research Scholar, Department of Pharmacy Practice, ISF College of Pharmacy, Moga-142001, Punjab, India
| | - Shamsher Singh
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga-142001, Punjab, India
| | - G D Gupta
- Department of Pharmaceutics, ISF College of Pharmacy, Moga-142001, Punjab, India
| | - Rohit
- Research Scholar, Department of Pharmacy Practice, ISF College of Pharmacy, Moga-142001, Punjab, India
| |
Collapse
|
5
|
Lin DJ, Hu DX, Wu QT, Huang LG, Lin ZH, Xu JT, He XX, Wu L. Analysis of influencing factors of washed microbiota transplantation in treating patients with metabolic syndrome. Front Nutr 2025; 12:1508381. [PMID: 39963663 PMCID: PMC11830617 DOI: 10.3389/fnut.2025.1508381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 01/13/2025] [Indexed: 02/20/2025] Open
Abstract
Background and aims Metabolic Syndrome (MS) is a cluster of metabolic abnormalities closely associated with hypertension, diabetes, hyperlipidemia, obesity, etc. Our previous research indicated that fecal microbiota transplantation (FMT) could improve MS, but the factors influencing the efficacy of washed microbiota transplantation (WMT) in treating MS patients remain unclear. The objective of this study is to analyze the influencing factors of WMT in treating MS patients. Methods The clinical data and influencing factors related to MS patients were collected retrospectively. Not only the changes in body mass index [BMI = weight (kg)/height (m)2], blood glucose, blood lipids, and blood pressure were analyzed, but also the influencing factors of WMT in treating MS patients were carried out based on Logistic Regression. The 16S rRNA gene amplicon sequencing was performed on fecal samples before and after WMT treatment. Results A total of 210 patients were included, including 68 patients in the WMT group and 142 patients in the drug treatment (DT) group. WMT had a significant improvement and ASCVD downregulation effect on MS patients, and 42.65% of MS patients removed the label of MS after WMT treatment. Independent influencing factors for treating MS patients through WMT include age < 60 years old, high smoking index, infection, single donor selection, single-course WMT treatment, and having hypertension, diabetes, or obesity. WMT treated MS patients by maintaining the balance of gut microbiota. Conclusions WMT has a significant effect in improving MS and downregulating ASCVD risk stratification. The therapeutic effect of WMT on MS patients is closely related to their age, smoking index, infection, chronic disease status, donor type, and WMT courses. Therefore, we can improve the efficacy of WMT by reducing independent influencing factors that affect gut microbiota homeostasis.
Collapse
Affiliation(s)
- De-Jiang Lin
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Dong-Xia Hu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Qing-Ting Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Lin-Gui Huang
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Zi-Han Lin
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Jia-Ting Xu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xing-Xiang He
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Lei Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- School of Biological Sciences and Engineering, South China University of Technology, Guangzhou, China
| |
Collapse
|
6
|
Hoang Nguyen KH, Le NV, Nguyen PH, Nguyen HHT, Hoang DM, Huynh CD. Human immune system: Exploring diversity across individuals and populations. Heliyon 2025; 11:e41836. [PMID: 39911431 PMCID: PMC11795082 DOI: 10.1016/j.heliyon.2025.e41836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 12/23/2024] [Accepted: 01/08/2025] [Indexed: 02/07/2025] Open
Abstract
The immune response is an intricate system that involves the complex connection of cellular and molecular components, each with distinct functional specialisations. It has a distinct capacity to adjust and mould the immune response in accordance with specific stimuli, influenced by both genetic and environmental factors. The presence of genetic diversity, particularly across different ethnic and racial groups, significantly contributes to the impact of incidence of diseases, disease susceptibility, autoimmune disorders, and cancer risks in specific regions and certain populations. Environmental factors, including geography and socioeconomic status, further modulate the variety of the immune system responses. These, in turn, affect the susceptibility to infectious diseases and development of autoimmune disorders. Despite the complexity of the relationship, there remains a gap in understanding the specificity of immune indices across races, immune reference ranges among populations, highlighting the need for deeper understanding of immune diversity for personalized approaches in diagnostics and therapeutics. This review systematically organizes these findings, with the goal of emphasizing the potential of targeted interventions to address health disparities and advance translational research, enabling a more comprehensive strategy. This approach promises significant advancements in identifying specific immunological conditions, focusing on personalized interventions, through both genetic and environmental factors.
Collapse
Affiliation(s)
| | - Nghi Vinh Le
- College of Health Sciences, VinUniversity, Hanoi, Viet Nam
| | | | - Hien Hau Thi Nguyen
- College of Health Sciences, VinUniversity, Hanoi, Viet Nam
- Institute of Research and Development, Duy Tan University, Da Nang, Viet Nam
- School of Medicine and Pharmacy, Duy Tan University, Da Nang, Viet Nam
| | - Duy Mai Hoang
- College of Health Sciences, VinUniversity, Hanoi, Viet Nam
| | | |
Collapse
|
7
|
Ding T, Liu C, Li Z. The mycobiome in human cancer: analytical challenges, molecular mechanisms, and therapeutic implications. Mol Cancer 2025; 24:18. [PMID: 39815314 PMCID: PMC11734361 DOI: 10.1186/s12943-025-02227-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 01/06/2025] [Indexed: 01/18/2025] Open
Abstract
The polymorphic microbiome is considered a new hallmark of cancer. Advances in High-Throughput Sequencing have fostered rapid developments in microbiome research. The interaction between cancer cells, immune cells, and microbiota is defined as the immuno-oncology microbiome (IOM) axis. Fungal microbes (the mycobiome), although representing only ∼ 0.1-1% of the microbiome, are a critical immunologically active component of the tumor microbiome. Accumulating evidence suggests a possible involvement of commensal and pathogenic fungi in cancer initiation, progression, and treatment responsiveness. The tumor-associated mycobiome mainly consists of the gut mycobiome, the oral mycobiome, and the intratumoral mycobiome. However, the role of fungi in cancer remains poorly understood, and the diversity and complexity of analytical methods make it challenging to access this field. This review aims to elucidate the causal and complicit roles of mycobiome in cancer development and progression while highlighting the issues that need to be addressed in executing such research. We systematically summarize the advantages and limitations of current fungal detection and analysis methods. We enumerate and integrate these recent findings into our current understanding of the tumor mycobiome, accompanied by the prospect of novel and exhilarating clinical implications.
Collapse
Affiliation(s)
- Ting Ding
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, Sichuan Province, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Chang Liu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, Sichuan Province, 610041, China
| | - Zhengyu Li
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, Sichuan Province, 610041, China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China.
| |
Collapse
|
8
|
Qiao T, Wen XH. Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies. World J Gastroenterol 2025; 31:100827. [PMID: 39811502 PMCID: PMC11684203 DOI: 10.3748/wjg.v31.i2.100827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 09/30/2024] [Accepted: 11/15/2024] [Indexed: 12/18/2024] Open
Abstract
Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.
Collapse
Affiliation(s)
- Tong Qiao
- Department of Clinical Medicine, Jinan University, Guangzhou 510632, Guangdong Province, China
| | - Xian-Hui Wen
- College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong Province, China
| |
Collapse
|
9
|
Wang Y, Bai M, Peng Q, Li L, Tian F, Guo Y, Jing C. Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease. Eur J Med Res 2024; 29:614. [PMID: 39710789 DOI: 10.1186/s40001-024-02224-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 12/15/2024] [Indexed: 12/24/2024] Open
Abstract
The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator. This abstract aims to elucidate the connection between the gut microbiota and angiogenesis in various diseases. The gut microbiota influences angiogenesis through various mechanisms, including the production of metabolites that directly or indirectly affect vascularization. For example, short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are known to regulate immune responses and inflammation, thereby affecting angiogenesis. In the context of cardiovascular diseases, the gut microbiota promotes atherosclerosis and vascular dysfunction by producing trimethylamine N-oxide (TMAO) and other metabolites that promote inflammation and endothelial dysfunction. Similarly, in neurodegenerative diseases, the gut microbiota may influence neuroinflammation and the integrity of the blood-brain barrier, thereby affecting angiogenesis. In cases of fractures and wound healing, the gut microbiota promotes angiogenesis by activating inflammatory responses and immune effects, facilitating the healing of tissue damage. In cancer, the gut microbiota can either inhibit or promote tumor growth and angiogenesis, depending on the specific bacterial composition and their metabolites. For instance, some bacteria can activate inflammasomes, leading to the production of inflammatory factors that alter the tumor immune microenvironment and activate angiogenesis-related signaling pathways, affecting tumor angiogenesis and metastasis. Some bacteria can directly interact with tumor cells, activating angiogenesis-related signaling pathways. Diet, as a modifiable factor, significantly influences angiogenesis through diet-derived microbial metabolites. Diet can rapidly alter the composition of the microbiota and its metabolic activity, thereby changing the concentration of microbial-derived metabolites and profoundly affecting the host's immune response and angiogenesis. For example, a high animal protein diet promotes the production of pro-atherogenic metabolites like TMAO, activating inflammatory pathways and interfering with platelet function, which is associated with the severity of coronary artery plaques, peripheral artery disease, and cardiovascular diseases. A diet rich in dietary fiber promotes the production of SCFAs, which act as ligands for cell surface or intracellular receptors, regulating various biological processes, including inflammation, tissue homeostasis, and immune responses, thereby influencing angiogenesis. In summary, the role of the gut microbiota in angiogenesis is multifaceted, playing an important role in disease progression by affecting various biological processes such as inflammation, immune responses, and multiple signaling pathways. Diet-derived microbial metabolites play a crucial role in linking the gut microbiota and angiogenesis. Understanding the complex interactions between diet, the gut microbiota, and angiogenesis has the potential to uncover novel therapeutic targets for managing these conditions. Therefore, interventions targeting the gut microbiota and its metabolites, such as through fecal microbiota transplantation (FMT) and the application of probiotics to alter the composition of the gut microbiota and enhance the production of beneficial metabolites, present a promising therapeutic strategy.
Collapse
Affiliation(s)
- Yan Wang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China
| | - Mingshuai Bai
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China
| | - Qifan Peng
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Feng Tian
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China.
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
| | - Ying Guo
- Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
| | - Changqing Jing
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China.
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
| |
Collapse
|
10
|
Khanna S. Microbiota restoration for recurrent Clostridioides difficile infection. Panminerva Med 2024; 66:417-426. [PMID: 39382853 DOI: 10.23736/s0031-0808.24.05111-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.
Collapse
Affiliation(s)
- Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA -
| |
Collapse
|
11
|
Wang Z, Wu X, Wang Y, Wen Q, Cui B, Zhang F. Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research. Therap Adv Gastroenterol 2024; 17:17562848241301574. [PMID: 39582897 PMCID: PMC11585053 DOI: 10.1177/17562848241301574] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 10/14/2024] [Indexed: 11/26/2024] Open
Abstract
The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.
Collapse
Affiliation(s)
- Zheyu Wang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Xia Wu
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Yaxue Wang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
| |
Collapse
|
12
|
Morales C, Ballestero L, Del Río P, Barbero-Herranz R, Olavarrieta L, Gómez-Artíguez L, Galeano J, Avendaño-Ortiz J, Basterra J, Del Campo R. Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor? Diagnostics (Basel) 2024; 14:2635. [PMID: 39682542 DOI: 10.3390/diagnostics14232635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 11/10/2024] [Accepted: 11/15/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVES Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors. METHODS Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated. RESULTS The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.
Collapse
Affiliation(s)
- Celia Morales
- Mikrobiomik Healthcare Company, 48160 Vizcaya, Spain
| | - Luna Ballestero
- Servicio de Microbiología, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
| | | | - Raquel Barbero-Herranz
- Servicio de Microbiología, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
| | - Leticia Olavarrieta
- Unidad Central de Apoyo (UCA-GT), Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
| | | | - Javier Galeano
- Grupo de Sistemas Complejos, Universidad Politécnica de Madrid, 28040 Madrid, Spain
| | - José Avendaño-Ortiz
- Servicio de Microbiología, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
- Ciber en Enfermedades Infecciosas CIBERINFEC, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Juan Basterra
- Mikrobiomik Healthcare Company, 48160 Vizcaya, Spain
| | - Rosa Del Campo
- Servicio de Microbiología, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
- Ciber en Enfermedades Infecciosas CIBERINFEC, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Facultad de Ciencias de la Salud, Universidad Alfonso X El Sabio, 28691 Villanueva de la Cañada, Spain
| |
Collapse
|
13
|
Hu X, Wu Q, Huang L, Xu J, He X, Wu L. Clinical efficacy of washed microbiota transplantation on metabolic syndrome and metabolic profile of donor outer membrane vesicles. Front Nutr 2024; 11:1465499. [PMID: 39628464 PMCID: PMC11611574 DOI: 10.3389/fnut.2024.1465499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 10/29/2024] [Indexed: 12/06/2024] Open
Abstract
Object To clarify the clinical efficacy of washed microbiota transplantation (WMT) for metabolic syndrome (MetS), and explore the differences in the metabolic profile of bacterial outer membrane vesicles (OMVs) in donor fecal bacteria suspension received by MetS patients with good and poor outcomes, and to construct a predictive model for the efficacy of WMT for MetS using differential metabolites. Methods Medical data 65 MetS patients who had completed at least 2 courses of WMT from 2017.05 to 2023.07 were collected. Fecal bacteria suspension of WMT donors were collected, and the clinical data of MetS patients treated with WMT during this period were collected as well. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared. OMVs were isolated from donor fecal bacteria suspension and off-target metabolomic sequencing was performed by Liquid Chromatograph Mass Spectrometer (LC-MS). Results Compared with baseline, Body mass index (BMI), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) of MetS patients showed significant decreases after the 1st (short-term) and 2nd (medium-term) courses, and fasting blood glucose (FBG) also showed significant decreases after the 1st session. There was a significant difference between the Marked Response OMVs and the Moderate Response OMVs. It was showed that 960 metabolites were significantly up-regulated in Marked Response OMVs and 439 metabolites that were significantly down-regulated. The ROC model suggested that 9-carboxymethoxymethylguanine, AUC = 0.8127, 95% CI [0.6885, 0.9369], was the most potent metabolite predicting the most available metabolite for efficacy. Conclusion WMT had significant short-term and medium-term clinical efficacy in MetS. There were differences in the structure of metabolites between Marked Response OMVs and Moderate Response OMVs. The level of 9-Carboxy methoxy methylguanine in Marked Response OMVs can be a good predictor of the efficacy of WMT in the treatment of MetS.
Collapse
Affiliation(s)
- Xuan Hu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Qingting Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Lingui Huang
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Jiating Xu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xingxiang He
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Lei Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- School of Biological Sciences and Engineering, South China University of Technology, Guangzhou, China
| |
Collapse
|
14
|
Al-Habsi N, Al-Khalili M, Haque SA, Elias M, Olqi NA, Al Uraimi T. Health Benefits of Prebiotics, Probiotics, Synbiotics, and Postbiotics. Nutrients 2024; 16:3955. [PMID: 39599742 PMCID: PMC11597603 DOI: 10.3390/nu16223955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/13/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024] Open
Abstract
The trillions of microbes that constitute the human gut microbiome play a crucial role in digestive health, immune response regulation, and psychological wellness. Maintaining gut microbiota is essential as metabolic diseases are associated with it. Functional food ingredients potentially improving gut health include prebiotics, probiotics, synbiotics, and postbiotics (PPSPs). While probiotics are living bacteria that provide health advantages when ingested sufficiently, prebiotics are non-digestible carbohydrates that support good gut bacteria. Synbiotics work together to improve immunity and intestinal health by combining probiotics and prebiotics. Postbiotics have also demonstrated numerous health advantages, such as bioactive molecules created during probiotic fermentation. According to a recent study, PPSPs can regulate the synthesis of metabolites, improve the integrity of the intestinal barrier, and change the gut microbiota composition to control metabolic illnesses. Additionally, the use of fecal microbiota transplantation (FMT) highlights the potential for restoring gut health through microbiota modulation, reinforcing the benefits of PPSPs in enhancing overall well-being. Research has shown that PPSPs provide several health benefits, such as improved immunological function, alleviation of symptoms associated with irritable bowel disease (IBD), decreased severity of allergies, and antibacterial and anti-inflammatory effects. Despite encouraging results, many unanswered questions remain about the scope of PPSPs' health advantages. Extensive research is required to fully realize the potential of these functional food components in enhancing human health and well-being. Effective therapeutic and prophylactic measures require further investigation into the roles of PPSPs, specifically their immune-system-modulating, cholesterol-lowering, antioxidant, and anti-inflammatory characteristics.
Collapse
Affiliation(s)
- Nasser Al-Habsi
- Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al-Khodh 123, Muscat P.O. Box 34, Oman; (M.A.-K.); (M.E.); (N.A.O.); (T.A.U.)
| | - Maha Al-Khalili
- Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al-Khodh 123, Muscat P.O. Box 34, Oman; (M.A.-K.); (M.E.); (N.A.O.); (T.A.U.)
| | - Syed Ariful Haque
- Department of Marine Science and Fisheries, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al-Khodh 123, Muscat P.O. Box 34, Oman
- Department of Fisheries, Bangamata Sheikh Fojilatunnesa Mujib Science and Technology University, Melandah, Jamalpur 2012, Bangladesh
| | - Moussa Elias
- Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al-Khodh 123, Muscat P.O. Box 34, Oman; (M.A.-K.); (M.E.); (N.A.O.); (T.A.U.)
| | - Nada Al Olqi
- Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al-Khodh 123, Muscat P.O. Box 34, Oman; (M.A.-K.); (M.E.); (N.A.O.); (T.A.U.)
| | - Tasnim Al Uraimi
- Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al-Khodh 123, Muscat P.O. Box 34, Oman; (M.A.-K.); (M.E.); (N.A.O.); (T.A.U.)
| |
Collapse
|
15
|
Ebrahimi R, Farsi Y, Nejadghaderi SA. Fecal microbiota transplantation for glaucoma; a potential emerging treatment strategy. CURRENT RESEARCH IN MICROBIAL SCIENCES 2024; 7:100314. [PMID: 39726974 PMCID: PMC11670420 DOI: 10.1016/j.crmicr.2024.100314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024] Open
Abstract
Glaucoma is the primary cause of irreversible blindness globally. Different glaucoma subtypes are identified by their underlying mechanisms, and treatment options differ by its pathogenesis. Current management includes topical medications to lower intraocular pressure and surgical procedures like trabeculoplasty and glaucoma drainage implants. Fecal microbiota transplantation (FMT) is an almost effective and safe treatment option for recurrent Clostridium difficile infection. The relationship between bacterial populations, metabolites, and inflammatory pathways in retinal diseases indicates possible therapeutic strategies. Thus, incorporating host microbiota-based therapies could offer an additional treatment option for glaucoma patients. Here, we propose that combining FMT with standard glaucoma treatments may benefit those affected by this condition. Also, the potential safety, efficacy, cost-effectiveness and clinical applications are discussed.
Collapse
Affiliation(s)
- Rasoul Ebrahimi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Yeganeh Farsi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Aria Nejadghaderi
- HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| |
Collapse
|
16
|
Caruso R, Lo BC, Chen GY, Núñez G. Host-pathobiont interactions in Crohn's disease. Nat Rev Gastroenterol Hepatol 2024:10.1038/s41575-024-00997-y. [PMID: 39448837 DOI: 10.1038/s41575-024-00997-y] [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] [Accepted: 09/23/2024] [Indexed: 10/26/2024]
Abstract
The mammalian intestine is colonized by trillions of microorganisms that are collectively referred to as the gut microbiota. The majority of symbionts have co-evolved with their host in a mutualistic relationship that benefits both. Under certain conditions, such as in Crohn's disease, a subtype of inflammatory bowel disease, some symbionts bloom to cause disease in genetically susceptible hosts. Although the identity and function of disease-causing microorganisms or pathobionts in Crohn's disease remain largely unknown, mounting evidence from animal models suggests that pathobionts triggering Crohn's disease-like colitis inhabit certain niches and penetrate the intestinal tissue to trigger inflammation. In this Review, we discuss the distinct niches occupied by intestinal symbionts and the evidence that pathobionts triggering Crohn's disease live in the mucus layer or near the intestinal epithelium. We also discuss how Crohn's disease-associated mutations in the host disrupt intestinal homeostasis by promoting the penetration and accumulation of pathobionts in the intestinal tissue. Finally, we discuss the potential role of microbiome-based interventions in precision therapeutic strategies for the treatment of Crohn's disease.
Collapse
Affiliation(s)
- Roberta Caruso
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
| | - Bernard C Lo
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Grace Y Chen
- Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Gabriel Núñez
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
| |
Collapse
|
17
|
Marsiglia R, Pane S, Del Chierico F, Russo A, Vernocchi P, Romani L, Cardile S, Diamanti A, Galli L, Tamborino A, Terlizzi V, De Angelis P, Angelino G, Putignani L. Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infections in a Cystic Fibrosis Child Previously Screen Positive, Inconclusive Diagnosis (CFSPID): A Case Report. Microorganisms 2024; 12:2059. [PMID: 39458368 PMCID: PMC11509880 DOI: 10.3390/microorganisms12102059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/10/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024] Open
Abstract
Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor-receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence.
Collapse
Affiliation(s)
- Riccardo Marsiglia
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Research Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (R.M.); (F.D.C.); (P.V.)
| | - Stefania Pane
- Unit of Microbiomics, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (S.P.); (A.R.)
| | - Federica Del Chierico
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Research Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (R.M.); (F.D.C.); (P.V.)
| | - Alessandra Russo
- Unit of Microbiomics, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (S.P.); (A.R.)
| | - Pamela Vernocchi
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Research Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (R.M.); (F.D.C.); (P.V.)
| | - Lorenza Romani
- Infectious Diseases Unit, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy;
| | - Sabrina Cardile
- Unit of Gastroenterology and Nutrition, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (S.C.); (A.D.); (P.D.A.); (G.A.)
| | - Antonella Diamanti
- Unit of Gastroenterology and Nutrition, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (S.C.); (A.D.); (P.D.A.); (G.A.)
| | - Luisa Galli
- Department of Health Sciences, University of Florence, 50121 Florence, Italy;
- Infectious Disease Unit, Meyer Children’s Hospital IRCCS, 50121 Florence, Italy;
| | - Agnese Tamborino
- Infectious Disease Unit, Meyer Children’s Hospital IRCCS, 50121 Florence, Italy;
| | - Vito Terlizzi
- Department of Pediatric Medicine, Meyer Children’s Hospital IRCCS, Cystic Fibrosis Regional Reference Center, Viale Gaetano Pieraccini 24, 50139 Florence, Italy;
| | - Paola De Angelis
- Unit of Gastroenterology and Nutrition, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (S.C.); (A.D.); (P.D.A.); (G.A.)
| | - Giulia Angelino
- Unit of Gastroenterology and Nutrition, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (S.C.); (A.D.); (P.D.A.); (G.A.)
| | - Lorenza Putignani
- Unit of Microbiomics and Unit of Research of Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| |
Collapse
|
18
|
Berry P, Khanna S. Fecal microbiota spores, live-brpk (VOWST™/VOS) for prevention of recurrent Clostridioides difficile infection. Future Microbiol 2024; 19:1519-1528. [PMID: 39320321 DOI: 10.1080/17460913.2024.2403892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 09/10/2024] [Indexed: 09/26/2024] Open
Abstract
Clostridioides difficile infection (CDI) is a health crisis comprising a majority of healthcare-associated infections and is now being seen in the community. Persistent dysbiosis despite treatment with standard-of-care antibiotics increases risk of recurrent infections. Fecal microbiota transplantation has been an effective way of addressing dysbiosis, but the studies have lacked standardization, which makes outcome and safety data difficult to interpret. Standardized microbiome therapies have demonstrated efficacy and safety for recurrent CDI and have been approved to prevent recurrent infection. In this review, we discuss the data behind and the practice use of fecal microbiota spores, live-brpk (VOWST™ / VOS), a US FDA approved live biotherapeutic for the prevention of recurrent CDI.
Collapse
Affiliation(s)
- Parul Berry
- C. difficile Clinic & Microbiome Restoration Program, Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Sahil Khanna
- C. difficile Clinic & Microbiome Restoration Program, Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| |
Collapse
|
19
|
Lauwers E, Sabino J, Hoffman I, van Hoeve K. Faecal microbiota transplantation in children: A systematic review. Acta Paediatr 2024; 113:1991-2002. [PMID: 38391047 DOI: 10.1111/apa.17167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/25/2024] [Accepted: 02/13/2024] [Indexed: 02/24/2024]
Abstract
AIM Novel technologies offer insights into the potential role of the intestinal microbiota in human health and disease. Dysbiosis has been associated with several diseases, and it is thought to play a role in the pathogenesis of different gastrointestinal diseases. Faecal microbiota transplantation (FMT) is emerging as a method to modulate the gastrointestinal microbial ecosystem. While recurrent Clostridioides difficile infection is the recognised FMT indication, exploration of other therapeutic uses is ongoing. METHODS Following PRISMA guidelines, we conducted a systematic review, extracting 583 articles from Embase and PubMed (index date to October 2022). RESULTS The search yielded 58 studies for full review, with 50 included in the systematic review. Articles were categorised by FMT indication, study design, efficacy, adverse events, donor selection and administration route. FMT appears safe and effective for recurrent Clostridioides difficile infection, although severe adverse events are reported in children. However, there are currently insufficient data to support the use of FMT for other potential therapeutic indications (such as irritable or inflammatory bowel disease or obesity), beside the potential to decolonise multi-drug resistant organisms. CONCLUSION This underscores the need for randomised, controlled, prospective cohort studies in children to assess FMT effectiveness in diverse conditions and counteract publication bias.
Collapse
Affiliation(s)
- Ella Lauwers
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| | - João Sabino
- TARGID, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ilse Hoffman
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| | - Karen van Hoeve
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| |
Collapse
|
20
|
Józefczuk P, Biliński J, Minkowska A, Łaguna P. Gut microbiome in children undergoing hematopoietic stem cell transplantation. Best Pract Res Clin Gastroenterol 2024; 72:101955. [PMID: 39645282 DOI: 10.1016/j.bpg.2024.101955] [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: 06/18/2024] [Revised: 10/10/2024] [Accepted: 10/22/2024] [Indexed: 12/09/2024]
Abstract
Hematopoietic stem cell transplantation (HSCT) is used in children as a treatment for various cancers, e.g. acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or other diseases, e.g. severe congenital immunodeficiency, metabolic disorders, hence the patient population is quite diverse. There is an increasing interest on the role of the microbiome in peri-transplant period. In this review, concepts of HSCT with the focus on the importance of microbiome composition, its changes during treatment and possible microbiota oriented interventions will be discussed. This paper analyzes data in pediatric population, but in view of interesting results and absence of analogous data for pediatric patients, it also looks at studies performed on adult population and pre-clinical trials on animals discussing possible translation to children.
Collapse
Affiliation(s)
- Paweł Józefczuk
- Department of Oncology, Pediatric Hematology, Clinical Transplantology and Pediatrics, Medical University of Warsaw, Poland.
| | - Jarosław Biliński
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Poland; Human Biome Institute, Gdansk, Warsaw, Poland
| | - Aleksandra Minkowska
- Department of Oncology, Pediatric Hematology, Clinical Transplantology and Pediatrics, Medical University of Warsaw, Poland
| | - Paweł Łaguna
- Department of Oncology, Pediatric Hematology, Clinical Transplantology and Pediatrics, Medical University of Warsaw, Poland
| |
Collapse
|
21
|
Fanizzi F, D'Amico F, Zanotelli Bombassaro I, Zilli A, Furfaro F, Parigi TL, Cicerone C, Fiorino G, Peyrin-Biroulet L, Danese S, Allocca M. The Role of Fecal Microbiota Transplantation in IBD. Microorganisms 2024; 12:1755. [PMID: 39338430 PMCID: PMC11433743 DOI: 10.3390/microorganisms12091755] [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: 08/07/2024] [Revised: 08/19/2024] [Accepted: 08/22/2024] [Indexed: 09/30/2024] Open
Abstract
Gut microbiota dysbiosis has a critical role in the pathogenesis of inflammatory bowel diseases, prompting the exploration of novel therapeutic approaches like fecal microbiota transplantation, which involves the transfer of fecal microbiota from a healthy donor to a recipient with the aim of restoring a balanced microbial community and attenuating inflammation. Fecal microbiota transplantation may exert beneficial effects in inflammatory bowel disease through modulation of immune responses, restoration of mucosal barrier integrity, and alteration of microbial metabolites. It could alter disease course and prevent flares, although long-term durability and safety data are lacking. This review provides a summary of current evidence on fecal microbiota transplantation in inflammatory bowel disease management, focusing on its challenges, such as variability in donor selection criteria, standardization of transplant protocols, and long-term outcomes post-transplantation.
Collapse
Affiliation(s)
- Fabrizio Fanizzi
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Isadora Zanotelli Bombassaro
- Department of Gastroenterology and Endoscopy, Santa Casa de Misericordia de Porto Alagre, Porto Alegre 90020-090, Brazil
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Clelia Cicerone
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Gionata Fiorino
- Department of Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, Nutrition-Genetics and Exposure to Environmental Risks Research Unit (NGERE), University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Fédération Hospitalo-Universitaire CARE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré-Hartmann, Paris IBD Center, F-92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy
| |
Collapse
|
22
|
Yamada CH, Ortis GB, Buso GM, Martins TC, Zequinao T, Telles JP, Wollmann LC, Montenegro CDO, Dantas LR, Cruz JW, Tuon FF. Validation of Lyophilized Human Fecal Microbiota for the Treatment of Clostridioides difficile Infection: A Pilot Study with Pharmacoeconomic Analysis of a Middle-Income Country-Promicrobioma Project. Microorganisms 2024; 12:1741. [PMID: 39203583 PMCID: PMC11356882 DOI: 10.3390/microorganisms12081741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/09/2024] [Accepted: 08/21/2024] [Indexed: 09/03/2024] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) represents a prevalent and potentially severe health concern linked to the usage of broad-spectrum antibiotics. The aim of this study was to evaluate a new lyophilized product based on human fecal microbiota for transplant, including cost-benefit analysis in the treatment of recurrent or refractory CDI. METHODS The product for fecal microbiota transplant was obtained from two donors. Microbiological, viability, and genomic analysis were evaluated. After validation, a clinical pilot study including recurrent or refractory CDI with 24 patients was performed. Clinical response and 4-week recurrence were the outcome. Cost-benefit analysis compared the fecal microbiota transplant with conventional retreatment with vancomycin or metronidazole. RESULTS The microbiota for transplant presented significant bacterial viability, with and adequate balance of Firmicutes and Bacteroidetes. The clinical response with the microbiota transplant was 92%. In financial terms, estimated expenditure for CDI solely related to recurrence, based on stochastic modeling, totals USD 222.8 million per year in Brazil. CONCLUSIONS The lyophilized human fecal microbiota for transplant is safe and can be an important step for a new product with low cost, even with genomic sequencing. Fecal microbiota transplantation emerges as a more cost-effective alternative compared to antimicrobials in the retreatment of CDI.
Collapse
Affiliation(s)
- Carolina Hikari Yamada
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - Gabriel Burato Ortis
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - Gustavo Martini Buso
- School of Business, Pontifical Catholic University of Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, PR, Brazil; (G.M.B.); (J.W.C.)
| | - Thalissa Colodiano Martins
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - Tiago Zequinao
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - Joao Paulo Telles
- Hospital Universitário Evangélico Mackenzie, Curitiba 80730-150, PR, Brazil; (J.P.T.); (L.C.W.)
| | | | - Carolina de Oliveira Montenegro
- School of Business, Pontifical Catholic University of Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, PR, Brazil; (G.M.B.); (J.W.C.)
| | - Leticia Ramos Dantas
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| | - June Westarb Cruz
- School of Business, Pontifical Catholic University of Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, PR, Brazil; (G.M.B.); (J.W.C.)
| | - Felipe Francisco Tuon
- Laboratory of Emerging Infectious Diseases, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil; (C.H.Y.); (G.B.O.); (T.C.M.); (T.Z.); (L.R.D.)
| |
Collapse
|
23
|
Hunt A, Drwiega E, Wang Y, Danziger L. A review of fecal microbiota, live-jslm for the prevention of recurrent Clostridioides difficile infection. Am J Health Syst Pharm 2024; 81:e402-e411. [PMID: 38470061 DOI: 10.1093/ajhp/zxae066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Indexed: 03/13/2024] Open
Abstract
PURPOSE To review the composition, preparation, proposed mechanism of action, safety, efficacy, and current place in therapy of Rebyota (fecal microbiota, live-jslm). SUMMARY As the first agent in a new class of drugs, live biotherapeutic products (LBPs), fecal microbiota, live-jslm offers another therapeutic approach for the prevention of recurrent Clostridioides difficile infection (rCDI). LBPs are given following antibiotic therapy for C. difficile to reintroduce certain bacteria present in the normal microbiome, as a means to reconstitute the microbiome of infected individuals. This review provides a summary of phase 2 and 3 clinical trials, product information, discussion of data limitations, and recommendations for place in therapy. High efficacy rates compared to placebo with sustained response up to 24 months after administration have been reported. The majority of adverse events identified were mild to moderate without significant safety signals. CONCLUSION Fecal microbiota, live-jslm has consistently been shown in randomized trials to be safe and effective in reducing rCDI. Its approval marks the culmination of decades of work to identify, characterize, and refine the intestinal microbiome to create pharmaceutical products.
Collapse
Affiliation(s)
- Aaron Hunt
- University of Illinois Chicago College of Pharmacy, Chicago, IL, USA
| | - Emily Drwiega
- University of Illinois Chicago College of Pharmacy, Chicago, IL, USA
| | - Yifan Wang
- University of Illinois Chicago College of Pharmacy, Chicago, IL, USA
| | - Larry Danziger
- University of Illinois Chicago College of Pharmacy, Chicago, IL, USA
| |
Collapse
|
24
|
Liang F, Song Y, Lin D, He H, Xu J, He X, Wu L. Washed Microbiota Transplantation Is Associated With Improved Lipid Profiles: Long-Term Efficacy and Safety in an Observational Cohort From South China. Clin Transl Gastroenterol 2024; 15:e00735. [PMID: 38920288 PMCID: PMC11272356 DOI: 10.14309/ctg.0000000000000735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024] Open
Abstract
INTRODUCTION Dyslipidemia is one of the main risk factors of chronic metabolic diseases. Our previous studies have shown that washed microbiota transplantation (WMT) has a significant improvement effect on patients with hyperlipidemia and hypolipemia in the Chinese population. The purpose of this study was to further explore the long-term efficacy and safety of WMT in patients with hyperlipidemia. METHODS Clinical data of patients who received WMT for multicourse were collected. Changes of blood lipid indexes before and after WMT, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein A, and Apolipoprotein B. RESULTS A total of 124 patients were enrolled, including 56 cases in the hyperlipidemia group and 68 cases with normal lipids. The mean observation time was 787.80 ± 371.45 days, and the longest follow-up time was 1,534 days. TC and non-HDL-C in the hyperlipidemia group with 1-4 courses of WMT were significantly reduced ( P < 0.05); TG decreased significantly after the second course ( P < 0.05); low-density lipoprotein cholesterol also significantly decreased after the fourth course of treatment ( P < 0.05); TG, TC, and non-HDL-C significantly decreased in single course, double course, and multiple course, respectively ( P < 0.05). In terms of time period, over 1 year, the improvement in multicourse treatment was more significant than the single and double-course ones. In terms of comprehensive efficacy, WMT restored 32.14% of patients in the hyperlipidemia group to the normal lipid group ( P < 0.001), of which 30.00% recovered to the normal lipid group within 1 year ( P = 0.004) and 65.38% were reassigned to the normal lipid group over 1 year ( P = 0.003). In addition, over the 1-year treatment period, WMT significantly degraded the high-risk and medium-risk groups of atherosclerotic cardiovascular disease risk stratification in hyperlipidemia cases. There were no serious adverse events. DISCUSSION WMT had a long-term improvement effect on patients with hyperlipidemia. The effect of multiple courses over 1 year was more significant than that of single/double courses and also had a significant destratification effect on the risk of atherosclerotic cardiovascular disease with high safety. Therefore, WMT provides a safe and long-term effective clinical treatment for patients with dyslipidemia.
Collapse
Affiliation(s)
- Fenfen Liang
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China;
| | - Youlin Song
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China;
| | - Dejiang Lin
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China;
| | - Hongxin He
- Sun Yat-sen University School of Medicine, Guangzhou, China.
| | - Jiating Xu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China;
| | - Xingxiang He
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China;
| | - Lei Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China;
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China;
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China;
| |
Collapse
|
25
|
Devavarapu PKV, Uppaluri KR, Nikhade VA, Palasamudram K, Sri Manjari K. Exploring the complexities of megacystis-microcolon-intestinal hypoperistalsis syndrome: insights from genetic studies. Clin J Gastroenterol 2024; 17:383-395. [PMID: 38461165 DOI: 10.1007/s12328-024-01934-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 01/30/2024] [Indexed: 03/11/2024]
Abstract
Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is an uncommon genetic disorder inherited in an autosomal recessive pattern that affects the muscles that line the bladder and intestines. The most common genes associated with MMIHS mutations are ACTG2, LMOD1, MYH11, MYL9, MYLK, and PDCL3. However, the complete genetic landscape of MMIHS still needs to be fully understood. The diagnosis of MMIHS can be challenging. However, advances in prenatal and diagnostic techniques, such as ultrasound and fetal urine analysis, have improved the ability to detect the syndrome early. Targeted next-generation sequencing (NGS) and other diagnostic tests can also diagnose MMIHS. The management of MMIHS involves addressing severe intestinal dysmotility, which often necessitates total parenteral nutrition (TPN), which can lead to complications such as hepatotoxicity and nutritional deficiencies. Multivisceral and intestinal transplantation has emerged as therapeutic options, offering the potential for improved outcomes and enteral autonomy. Understanding the genetic underpinnings of MMIHS is crucial for personalized care. While the prognosis varies, timely interventions and careful monitoring enhance patient outcomes. Genetic studies have given us valuable insights into the molecular mechanisms of MMIHS. These studies have identified mutations in genes involved in the development and function of smooth muscle cells. They have also shown that MMIHS is associated with defects in the signaling pathways that control muscle contraction. Continued research in the genetics of MMIHS holds promise for unraveling the complexities of MMIHS and improving the lives of affected individuals.
Collapse
Affiliation(s)
- Prasad K V Devavarapu
- Department of Biochemistry, GITAM Institute of Medical Sciences & Research, Rushikonda, Visakhapatnam, Andhra Pradesh, 530045, India
| | - Kalyan Ram Uppaluri
- GenepoweRx, Suit #2B, Plot No. 240, Nirvana, Road No. 36, Jawahar Colony, Jubilee Hills, Hyderabad, Telangana, 500033, India
| | - Vrushabh Anil Nikhade
- KIT's College of Engineering (Autonomous), Kolhapur, Maharashtra, 416234, India
- GenepoweRx, Suit #2B, Plot No. 240, Nirvana, Road No. 36, Jawahar Colony, Jubilee Hills, Hyderabad, Telangana, 500033, India
| | - Kalyani Palasamudram
- GenepoweRx, Suit #2B, Plot No. 240, Nirvana, Road No. 36, Jawahar Colony, Jubilee Hills, Hyderabad, Telangana, 500033, India
| | - Kavutharapu Sri Manjari
- GenepoweRx, Suit #2B, Plot No. 240, Nirvana, Road No. 36, Jawahar Colony, Jubilee Hills, Hyderabad, Telangana, 500033, India.
| |
Collapse
|
26
|
Pires L, González-Paramás AM, Heleno SA, Calhelha RC. The Role of Gut Microbiota in the Etiopathogenesis of Multiple Chronic Diseases. Antibiotics (Basel) 2024; 13:392. [PMID: 38786121 PMCID: PMC11117238 DOI: 10.3390/antibiotics13050392] [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: 04/04/2024] [Revised: 04/23/2024] [Accepted: 04/25/2024] [Indexed: 05/25/2024] Open
Abstract
Chronic diseases (CD) may result from a combination of genetic factors, lifestyle and social behaviours, healthcare system influences, community factors, and environmental determinants of health. These risk factors frequently coexist and interact with one another. Ongoing research and a focus on personalized interventions are pivotal strategies for preventing and managing chronic disease outcomes. A wealth of literature suggests the potential involvement of gut microbiota in influencing host metabolism, thereby impacting various risk factors associated with chronic diseases. Dysbiosis, the perturbation of the composition and activity of the gut microbiota, is crucial in the etiopathogenesis of multiple CD. Recent studies indicate that specific microorganism-derived metabolites, including trimethylamine N-oxide, lipopolysaccharide and uremic toxins, contribute to subclinical inflammatory processes implicated in CD. Various factors, including diet, lifestyle, and medications, can alter the taxonomic species or abundance of gut microbiota. Researchers are currently dedicating efforts to understanding how the natural progression of microbiome development in humans affects health outcomes. Simultaneously, there is a focus on enhancing the understanding of microbiome-host molecular interactions. These endeavours ultimately aim to devise practical approaches for rehabilitating dysregulated human microbial ecosystems, intending to restore health and prevent diseases. This review investigates how the gut microbiome contributes to CD and explains ways to modulate it for managing or preventing chronic conditions.
Collapse
Affiliation(s)
- Lara Pires
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (L.P.); (S.A.H.)
- Grupo de Investigación en Polifenoles en Alimentos, Implicaciones en la Calidad y en Salud Humana, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno s/n, 37007 Salamanca, Spain;
| | - Ana M. González-Paramás
- Grupo de Investigación en Polifenoles en Alimentos, Implicaciones en la Calidad y en Salud Humana, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno s/n, 37007 Salamanca, Spain;
| | - Sandrina A. Heleno
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (L.P.); (S.A.H.)
- Laboratório Associado para Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
| | - Ricardo C. Calhelha
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (L.P.); (S.A.H.)
- Laboratório Associado para Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
| |
Collapse
|
27
|
Stallmach A, von Müller L, Storr M, Link A, Konturek PC, Solbach PC, Weiss KH, Wahler S, Vehreschild MJGT. [Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:490-499. [PMID: 37187187 DOI: 10.1055/a-2075-2725] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
INTRODUCTION Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far. MATERIAL AND METHODOLOGY Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation. RESULTS Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%. DISCUSSION In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.
Collapse
Affiliation(s)
- Andreas Stallmach
- Klinik für Innere Medizin IV, Universitätsklinikum Jena, Jena, Deutschland
| | | | | | - Alexander Link
- Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Deutschland
| | - Peter C Konturek
- Thüringen-Klinik Saalfeld Georgius Agricola GmbH, Saalfeld, Deutschland
| | | | - Karl Heinz Weiss
- Krankenhaus Salem der Evang. Stadtmission Heidelberg gGmbH, Heidelberg, Deutschland
| | | | - Maria J G T Vehreschild
- Medizinische Klinik 2, Infektiologie, Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland
| |
Collapse
|
28
|
Kreitmann L, Helms J, Martin-Loeches I, Salluh J, Poulakou G, Pène F, Nseir S. ICU-acquired infections in immunocompromised patients. Intensive Care Med 2024; 50:332-349. [PMID: 38197931 DOI: 10.1007/s00134-023-07295-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 11/25/2023] [Indexed: 01/11/2024]
Abstract
Immunocompromised patients account for an increasing proportion of the typical intensive care unit (ICU) case-mix. Because of the increased availability of new drugs for cancer and auto-immune diseases, and improvement in the care of the most severely immunocompromised ICU patients (including those with hematologic malignancies), critically ill immunocompromised patients form a highly heterogeneous patient population. Furthermore, a large number of ICU patients with no apparent immunosuppression also harbor underlying conditions altering their immune response, or develop ICU-acquired immune deficiencies as a result of sepsis, trauma or major surgery. While infections are associated with significant morbidity and mortality in immunocompromised critically ill patients, little specific data are available on the incidence, microbiology, management and outcomes of ICU-acquired infections in this population. As a result, immunocompromised patients are usually excluded from trials and guidelines on the management of ICU-acquired infections. The most common ICU-acquired infections in immunocompromised patients are ventilator-associated lower respiratory tract infections (which include ventilator-associated pneumonia and tracheobronchitis) and bloodstream infections. Recently, several large observational studies have shed light on some of the epidemiological specificities of these infections-as well as on the dynamics of colonization and infection with multidrug-resistant bacteria-in these patients, and these will be discussed in this review. Immunocompromised patients are also at higher risk than non-immunocompromised hosts of fungal and viral infections, and the diagnostic and therapeutic management of these infections will be covered. Finally, we will suggest some important areas of future investigation.
Collapse
Affiliation(s)
- Louis Kreitmann
- Department of Intensive Care Medicine, Imperial College Healthcare NHS Trust, London, UK
- Centre for Antimicrobial Optimisation, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, W12 0HS, UK
| | - Julie Helms
- Service de Médecine Intensive-Réanimation, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
- ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Fédération Hospitalo-Universitaire (FHU) OMICARE, Université de Strasbourg (UNISTRA), Strasbourg, France
| | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), Leinster, D08NYH1, Dublin, Ireland
- Pulmonary Intensive Care Unit, Respiratory Institute, Hospital Clinic of Barcelona, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, ICREA CIBERes, 08380, Barcelona, Spain
| | - Jorge Salluh
- D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Rio de Janeiro, RJ, 22281-100, Brazil
| | - Garyphallia Poulakou
- Third Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece
| | - Frédéric Pène
- Médecine Intensive-Réanimation, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
- Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Cité, Paris, France
| | - Saad Nseir
- Médecine Intensive-Réanimation, CHU de Lille, 59000, Lille, France.
- Inserm U1285, Université de Lille, CNRS, UMR 8576-UGSF, 59000, Lille, France.
| |
Collapse
|
29
|
Monday L, Tillotson G, Chopra T. Microbiota-Based Live Biotherapeutic Products for Clostridioides Difficile Infection- The Devil is in the Details. Infect Drug Resist 2024; 17:623-639. [PMID: 38375101 PMCID: PMC10876012 DOI: 10.2147/idr.s419243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 02/12/2024] [Indexed: 02/21/2024] Open
Abstract
Clostridioides difficile infection (CDI) remains a significant contributor to healthcare costs and morbidity due to high rates of recurrence. Currently, available antibiotic treatment strategies further disrupt the fecal microbiome and do not address the alterations in commensal flora (dysbiosis) that set the stage for CDI. Advances in microbiome-based research have resulted in the development of new agents, classified as live biotherapeutic products (LBPs), for preventing recurrent CDI (rCDI) by restoring eubiosis. Prior to the LBPs, fecal microbiota transplantation (FMT) was available for this purpose; however, lack of large-scale availability and safety concerns have remained barriers to its widespread use. The LBPs are an exciting development, but questions remain. Some are derived directly from human stool while other developmental products contain a defined microbial consortium manufactured ex vivo, and they may be composed of either living bacteria or their spores, making it difficult to compare members of this heterogenous drug class to one another. None have been studied head-to head or against FMT in preventing rCDI. As a class, they have considerable variability in their biologic composition, biopharmaceutic science, route of administration, stages of development, and clinical trial data. This review will start by explaining the role of dysbiosis in CDI, then give the details of the biopharmaceutical components for the LBPs which are approved or in development including how they differ from FMT and from one another. We then discuss the clinical trials of the LBPs currently approved for rCDI and end with the future clinical directions of LBPs beyond C. difficile.
Collapse
Affiliation(s)
- Lea Monday
- Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI, USA
| | | | - Teena Chopra
- Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI, USA
| |
Collapse
|
30
|
Linnehan BK, Kodera SM, Allard SM, Brodie EC, Allaband C, Knight R, Lutz HL, Carroll MC, Meegan JM, Jensen ED, Gilbert JA. Evaluation of the safety and efficacy of fecal microbiota transplantations in bottlenose dolphins (Tursiops truncatus) using metagenomic sequencing. J Appl Microbiol 2024; 135:lxae026. [PMID: 38305096 PMCID: PMC10853691 DOI: 10.1093/jambio/lxae026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/28/2023] [Accepted: 01/31/2024] [Indexed: 02/03/2024]
Abstract
AIMS Gastrointestinal disease is a leading cause of morbidity in bottlenose dolphins (Tursiops truncatus) under managed care. Fecal microbiota transplantation (FMT) holds promise as a therapeutic tool to restore gut microbiota without antibiotic use. This prospective clinical study aimed to develop a screening protocol for FMT donors to ensure safety, determine an effective FMT administration protocol for managed dolphins, and evaluate the efficacy of FMTs in four recipient dolphins. METHODS AND RESULTS Comprehensive health monitoring was performed on donor and recipient dolphins. Fecal samples were collected before, during, and after FMT therapy. Screening of donor and recipient fecal samples was accomplished by in-house and reference lab diagnostic tests. Shotgun metagenomics was used for sequencing. Following FMT treatment, all four recipient communities experienced engraftment of novel microbial species from donor communities. Engraftment coincided with resolution of clinical signs and a sustained increase in alpha diversity. CONCLUSION The donor screening protocol proved to be safe in this study and no adverse effects were observed in four recipient dolphins. Treatment coincided with improvement in clinical signs.
Collapse
Affiliation(s)
| | - Sho M Kodera
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92037, United States
| | - Sarah M Allard
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92037, United States
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, United States
| | - Erin C Brodie
- National Marine Mammal Foundation, San Diego, CA 92106, United States
| | - Celeste Allaband
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, United States
| | - Rob Knight
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, United States
- Center for Microbiome Innovation, Joan and Irwin Jacobs School of Engineering, University of California San Diego, La Jolla, CA 92093, United States
- Department of Medicine, University of California San Diego, La Jolla, CA 92161, United States
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, United States
- Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, United States
| | - Holly L Lutz
- Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, United States
| | | | - Jennifer M Meegan
- National Marine Mammal Foundation, San Diego, CA 92106, United States
| | - Eric D Jensen
- U.S. Navy Marine Mammal Program, Naval Information Warfare Center Pacific, San Diego, CA 92106, United States
| | - Jack A Gilbert
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92037, United States
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, United States
- Center for Microbiome Innovation, Joan and Irwin Jacobs School of Engineering, University of California San Diego, La Jolla, CA 92093, United States
| |
Collapse
|
31
|
Shah YR, Ali H, Tiwari A, Guevara-Lazo D, Nombera-Aznaran N, Pinnam BSM, Gangwani MK, Gopakumar H, Sohail AH, Kanumilli S, Calderon-Martinez E, Krishnamoorthy G, Thakral N, Dahiya DS. Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions. World J Hepatol 2024; 16:17-32. [PMID: 38313244 PMCID: PMC10835490 DOI: 10.4254/wjh.v16.i1.17] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 12/02/2023] [Accepted: 01/03/2024] [Indexed: 01/23/2024] Open
Abstract
Fecal microbiota transplantation (FMT) offers a potential treatment avenue for hepatic encephalopathy (HE) by leveraging beneficial bacterial displacement to restore a balanced gut microbiome. The prevalence of HE varies with liver disease severity and comorbidities. HE pathogenesis involves ammonia toxicity, gut-brain communication disruption, and inflammation. FMT aims to restore gut microbiota balance, addressing these factors. FMT's efficacy has been explored in various conditions, including HE. Studies suggest that FMT can modulate gut microbiota, reduce ammonia levels, and alleviate inflammation. FMT has shown promise in alcohol-associated, hepatitis B and C-associated, and non-alcoholic fatty liver disease. Benefits include improved liver function, cognitive function, and the slowing of disease progression. However, larger, controlled studies are needed to validate its effectiveness in these contexts. Studies have shown cognitive improvements through FMT, with potential benefits in cirrhotic patients. Notably, trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care. Although evidence is promising, challenges remain: Limited patient numbers, varied dosages, administration routes, and donor profiles. Further large-scale, controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy. While FMT holds potential for HE management, ongoing research is needed to address these challenges, optimize protocols, and expand its availability as a therapeutic option for diverse hepatic conditions.
Collapse
Affiliation(s)
- Yash R Shah
- Department of Internal Medicine, Trinity Health Oakland/Wayne State University, Pontiac, MI 48341, United States
| | - Hassam Ali
- Division of Gastroenterology and Hepatology, East Carolina University/Brody School of Medicine, Greenville, NC 27858, United States
| | - Angad Tiwari
- Department of Internal Medicine, Maharani Laxmi Bai Medical College, Jhansi 284001, India
| | - David Guevara-Lazo
- Faculty of Medicine, Universidad Peruana Cayetano Heredia, Lima 15102, Peru
| | | | - Bhanu Siva Mohan Pinnam
- Department of Internal Medicine, John H. Stroger Hospital of Cook County, Chicago, IL 60612, United States
| | - Manesh Kumar Gangwani
- Department of Internal Medicine, The University of Toledo, Toledo, OH 43606, United States
| | - Harishankar Gopakumar
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, United States
| | - Amir H Sohail
- Department of Surgery, University of New Mexico, Albuquerque, NM 87106, United States
| | | | - Ernesto Calderon-Martinez
- Department of Internal Medicine, Universidad Nacional Autonoma de Mexico, Ciudad De Mexico 04510, Mexico
| | - Geetha Krishnamoorthy
- Department of Internal Medicine, Trinity Health Oakland/Wayne State University, Pontiac, MI 48341, United States
| | - Nimish Thakral
- Department of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY 40536, United States
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, United States.
| |
Collapse
|
32
|
Borrego-Ruiz A, Borrego JJ. An updated overview on the relationship between human gut microbiome dysbiosis and psychiatric and psychological disorders. Prog Neuropsychopharmacol Biol Psychiatry 2024; 128:110861. [PMID: 37690584 DOI: 10.1016/j.pnpbp.2023.110861] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 09/06/2023] [Accepted: 09/06/2023] [Indexed: 09/12/2023]
Abstract
There is a lot of evidence establishing that nervous system development is related to the composition and functions of the gut microbiome. In addition, the central nervous system (CNS) controls the imbalance of the intestinal microbiota, constituting a bidirectional communication system. At present, various gut-brain crosstalk routes have been described, including immune, endocrine and neural circuits via the vagal pathway. Several empirical data have associated gut microbiota alterations (dysbiosis) with neuropsychiatric diseases, such as Alzheimer's disease, autism and Parkinson's disease, and with other psychological disorders, like anxiety and depression. Fecal microbiota transplantation (FMT) therapy has shown that the gut microbiota can transfer behavioral features to recipient animals, which provides strong evidence to establish a causal-effect relationship. Interventions, based on prebiotics, probiotics or synbiotics, have demonstrated an important influence of microbiota on neurological disorders by the synthesis of neuroactive compounds that interact with the nervous system and by the regulation of inflammatory and endocrine processes. Further research is needed to demonstrate the influence of gut microbiota dysbiosis on psychiatric and psychological disorders, and how microbiota-based interventions may be used as potential therapeutic tools.
Collapse
Affiliation(s)
- Alejandro Borrego-Ruiz
- Departamento de Psicología Social y de las Organizaciones, Facultad de Psicología, UNED, Madrid, Spain
| | - Juan J Borrego
- Departamento de Microbiología, Universidad de Málaga, Málaga, Spain.
| |
Collapse
|
33
|
Niccolai E, Martinelli I, Quaranta G, Nannini G, Zucchi E, De Maio F, Gianferrari G, Bibbò S, Cammarota G, Mandrioli J, Masucci L, Amedei A. Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis: Clinical Protocol and Evaluation of Microbiota Immunity Axis. Methods Mol Biol 2024; 2761:373-396. [PMID: 38427251 DOI: 10.1007/978-1-0716-3662-6_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
The fecal microbial transplantation (FMT) is a therapeutic transplant of fecal microbiota from healthy donors to patients. This practice is aimed at restoring eubiosis and rebalancing the enteric and systemic immune responses, and then eliminating pathogenic triggers of multiple disease, including neurodegenerative diseases. Alterations of gut microbiota (GM) affect the central nervous system (CNS) health, impacting neuro-immune interactions, synaptic plasticity, myelination, and skeletal muscle function. T-regulatory lymphocytes (Treg) are among the most important players in the pathogenesis of amyotrophic lateral sclerosis (ALS), altering the disease course. Along with circulating neuropeptides, other immune cells, and the gut-brain axis, the GM influences immunological tolerance and controls Treg's number and suppressive functions. A double-blind, controlled, multicenter study on FMT in ALS patients has been designed to evaluate if FMT can modulate neuroinflammation, by restoring Treg number, thus modifying disease activity and progression.
Collapse
Affiliation(s)
- Elena Niccolai
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Ilaria Martinelli
- Neurology Unit, Department of Neuroscience, Azienda Ospedaliero Universitaria di Modena, Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Gianluca Quaranta
- Department of Laboratory and Infectious Sciences, A. Gemelli University Hospital IRCCS, Rome, Italy
| | - Giulia Nannini
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Elisabetta Zucchi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Flavio De Maio
- Department of Laboratory and Infectious Sciences, A. Gemelli University Hospital IRCCS, Rome, Italy
| | - Giulia Gianferrari
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Stefano Bibbò
- Digestive Disease Center, A. Gemelli University Hospital IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, A. Gemelli University Hospital IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Jessica Mandrioli
- Neurology Unit, Department of Neuroscience, Azienda Ospedaliero Universitaria di Modena, Modena, Italy
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Luca Masucci
- Department of Laboratory and Infectious Sciences, A. Gemelli University Hospital IRCCS, Rome, Italy.
- Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Catholic University of Sacred Heart, Rome, Italy.
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
- Internal Interdisciplinary Medicine Unit, Careggi University Hospital, Florence, Italy.
| |
Collapse
|
34
|
Levy EI, Dinleyici M, Dinleyici E, Vandenplas Y. Clostridioides difficile Infections: Prevention and Treatment Strategies. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1449:175-186. [PMID: 39060738 DOI: 10.1007/978-3-031-58572-2_11] [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: 07/28/2024]
Abstract
Clostridioides difficile is the most common causative agent of antibiotic-associated diarrhea. This spore forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, more recent fecal microbiota transplantation has also been valid as a therapy. The use of probiotics, especially Saccharomyces boulardii CNCM I-745 have become valid forms of prevention therapy. Although there are studies in adults with microbiota-targeted new generation therapies and Clostridium difficile vaccines, there are no data in the paediatric age group yet.
Collapse
Affiliation(s)
- Elvira Ingrid Levy
- Department of Pediatrics, C.H.U. Saint-Pieter, Free University of Brussels, Brussels, Belgium
| | - Meltem Dinleyici
- Eskisehir Osmangazi University Faculty of Medicine, Department of Social Pediatrics, Eskisehir, Turkey
| | - Ener Dinleyici
- Department of Pediatrics, Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey
| | - Yvan Vandenplas
- Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium.
| |
Collapse
|
35
|
Zhang L, Ma XG. A Comprehensive Review on Biotransformation, Interaction, and Health of Gut Microbiota and Bioactive Components. Comb Chem High Throughput Screen 2024; 27:1551-1565. [PMID: 37916626 DOI: 10.2174/0113862073257733231011072004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 08/25/2023] [Accepted: 09/06/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND The relationship between gut microbiota and bioactive components has become the research focus in the world. We attempted to clarify the relationship between biotransformation and metabolites of gut microbiota and bioactive components, and explore the metabolic pathway and mechanism of bioactive ingredients in vivo, which will provide an important theoretical basis for the clinical research of bioactive ingredients and rationality of drugs, and also provide an important reference for the development of new drugs with high bioavailability. METHODS The related references of this review on microbiota and bioactive components were collected from both online and offline databases, such as ScienceDirect, PubMed, Elsevier, Willy, SciFinder, Google Scholar, Web of Science, Baidu Scholar, SciHub, Scopus, and CNKI. RESULTS This review summarized the biotransformation of bioactive components under the action of gut microbiota, including flavonoids, terpenoids, phenylpropanoids, alkaloids, steroids, and other compounds. The interaction of bioactive components and gut microbiota is a key link for drug efficacy. Relevant research is crucial to clarify bioactive components and their mechanisms, which involve the complex interaction among bioactive components, gut microbiota, and intestinal epithelial cells. This review also summarized the individualized, precise, and targeted intervention of gut microbiota in the field of intestinal microorganisms from the aspects of dietary fiber, microecological agents, fecal microbiota transplantation, and postbiotics. It will provide an important reference for intestinal microecology in the field of nutrition and health for people. CONCLUSION To sum up, the importance of human gut microbiota in the research of bioactive components metabolism and transformation has attracted the attention of scholars all over the world. It is believed that with the deepening of research, human gut microbiota will be more widely used in the pharmacodynamic basis, drug toxicity relationship, new drug discovery, drug absorption mechanism, and drug transport mechanism in the future.
Collapse
Affiliation(s)
- Lin Zhang
- Department of Medical Nursing, Jiyuan Vocational and Technical College, 459000 Jiyuan, Henan, P.R. China
| | - Xiao-Gen Ma
- Department of Medical Nursing, Jiyuan Vocational and Technical College, 459000 Jiyuan, Henan, P.R. China
| |
Collapse
|
36
|
Huang H, Wang Q, Yang Y, Zhong W, He F, Li J. The mycobiome as integral part of the gut microbiome: crucial role of symbiotic fungi in health and disease. Gut Microbes 2024; 16:2440111. [PMID: 39676474 PMCID: PMC11651280 DOI: 10.1080/19490976.2024.2440111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 11/27/2024] [Accepted: 12/04/2024] [Indexed: 12/17/2024] Open
Abstract
The gut mycobiome significantly affects host health and immunity. However, most studies have focused on symbiotic bacteria in the gut microbiome, whereas less attention has been given to symbiotic fungi. Although fungi constitute only 0.01%-0.1% of the gut microbiome, their larger size and unique immunoregulatory functions make them significant. Factors like diet, antimicrobials use, and age can disrupt the fungal community, leading to dysbiosis. Fungal-bacterial-host immune interactions are critical in maintaining gut homeostasis, with fungi playing a role in mediating immune responses such as Th17 cell activation. This review highlights methods for studying gut fungi, the composition and influencing factors of the gut mycobiome, and its potential in therapeutic interventions for intestinal and hepatic diseases. We aim to provide new insights into the underexplored role of gut fungi in human health.
Collapse
Affiliation(s)
- Hui Huang
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
- Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, P. R. China
| | - Qiurong Wang
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
- Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, P. R. China
| | - Ying Yang
- Department of Gastroenterology, Sichuan Fifth People’s Hospital, Chengdu, China
| | - Wei Zhong
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
| | - Feng He
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
- Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, P. R. China
| | - Jun Li
- Department of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, P. R. China
- Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, P. R. China
| |
Collapse
|
37
|
Gonzales-Luna AJ, Carlson TJ, Garey KW. Review Article: Safety of Live Biotherapeutic Products Used for the Prevention of Clostridioides difficile Infection Recurrence. Clin Infect Dis 2023; 77:S487-S496. [PMID: 38051970 DOI: 10.1093/cid/ciad642] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023] Open
Abstract
Live biotherapeutic products (LBPs) represent a new class of therapeutics indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in adults. However, microbiota-based therapies have been used in CDI management before the Food and Drug Administration (FDA) designated this new drug class. The regulation of these microbiome-based therapies has varied, and several safety concerns have arisen over time. Requirements established by the FDA regarding the development of LBPs minimizes many of these prior concerns, and phase III trials have proven the safety and efficacy of 2 stool donor-derived LBPs: fecal microbiota, live-jslm (Rebyota™; formerly RBX2660) and fecal microbiota spores, live-brpk (Vowst™; formerly SER-109). Mild gastrointestinal side effects are common, but no severe drug-related adverse events have been reported with their use to date. A third LBP entering phase III clinical trials, VE303, follows a novel approach by sourcing bacterial strains from clonal cell banks and has demonstrated a similarly favorable safety profile.
Collapse
Affiliation(s)
- Anne J Gonzales-Luna
- Department of Pharmacy and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
| | - Travis J Carlson
- Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, San Antonio, Texas, USA
- Pharmacotherapy Education and Research Center, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA
- University Hospital, University Health, San Antonio, Texas, USA
| | - Kevin W Garey
- Department of Pharmacy and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
| |
Collapse
|
38
|
D T, Venkatesh MP. Fecal microbiota transplantation: History, procedure and regulatory considerations. Presse Med 2023; 52:104204. [PMID: 37944641 DOI: 10.1016/j.lpm.2023.104204] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 08/07/2023] [Accepted: 10/25/2023] [Indexed: 11/12/2023] Open
Abstract
Fecal microbiota transplantation (FMT) is a medical treatment which involves the transfer of feces from a healthy donor to a recipient to restore the balance of gut microbiota and improve clinical outcomes. FMT has gained recognition in recent years due to its effectiveness in treating recurrent Clostridioides difficile infections (rCDI) and other gastrointestinal disorders. Additionally, it has been studied as an intervention for some other conditions, like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This review covers regulatory considerations related to FMT, including the current state of FMT regulation and the need for further research to fully understand the safety and efficacy of this treatment. For transplantation of fecal microbiota, the Food and Drug Administration (FDA) classifies the treatment as an investigational new drug (IND), which typically requires physicians and scientists to submit an IND application. Ethical issues surrounding FMT, including the necessity of informed consent from donors and recipients and the potential transmission of infectious agents, are also discussed. Overall, FMT has the potential to offer significant therapeutic benefits, but it also raises regulatory and ethical considerations that require careful consideration. Further research is necessary to fully comprehend risks and benefits of FMT and to develop guidelines for its use in clinical practice.
Collapse
Affiliation(s)
- Thanush D
- Research Student - Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education Research, Mysuru, Karnataka, India
| | - M P Venkatesh
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education Research, S.S. Nagar, Mysuru, 570015 Karnataka, India; Faculty of Pharmaceutical Sciences, UCSI University, Malaysia.
| |
Collapse
|
39
|
de Nies L, Kobras CM, Stracy M. Antibiotic-induced collateral damage to the microbiota and associated infections. Nat Rev Microbiol 2023; 21:789-804. [PMID: 37542123 DOI: 10.1038/s41579-023-00936-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2023] [Indexed: 08/06/2023]
Abstract
Antibiotics have transformed medicine, saving millions of lives since they were first used to treat a bacterial infection. However, antibiotics administered to target a specific pathogen can also cause collateral damage to the patient's resident microbial population. These drugs can suppress the growth of commensal species which provide protection against colonization by foreign pathogens, leading to an increased risk of subsequent infection. At the same time, a patient's microbiota can harbour potential pathogens and, hence, be a source of infection. Antibiotic-induced selection pressure can cause overgrowth of resistant pathogens pre-existing in the patient's microbiota, leading to hard-to-treat superinfections. In this Review, we explore our current understanding of how antibiotic therapy can facilitate subsequent infections due to both loss of colonization resistance and overgrowth of resistant microorganisms, and how these processes are often interlinked. We discuss both well-known and currently overlooked examples of antibiotic-associated infections at various body sites from various pathogens. Finally, we describe ongoing and new strategies to overcome the collateral damage caused by antibiotics and to limit the risk of antibiotic-associated infections.
Collapse
Affiliation(s)
- Laura de Nies
- Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
| | - Carolin M Kobras
- Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
| | - Mathew Stracy
- Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
| |
Collapse
|
40
|
Xiang W, Xiang H, Wang J, Jiang Y, Pan C, Ji B, Zhang A. Fecal microbiota transplantation: a novel strategy for treating Alzheimer's disease. Front Microbiol 2023; 14:1281233. [PMID: 38033557 PMCID: PMC10687436 DOI: 10.3389/fmicb.2023.1281233] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 10/31/2023] [Indexed: 12/02/2023] Open
Abstract
Alzheimer's disease is a common neurological disorder, which has become one of the major factors affecting human health due to its serious impact on individuals, families and society. It has been confirmed that gut microbiota can affect the occurrence and development of Alzheimer's disease. Especially, fecal microbiota transplantation plays a positive role in the treatment of Alzheimer's disease. The mechanisms for improving Alzheimer's disease might include anti-inflammation and regulation of amyloid β-protein, synaptic plasticity, short-chain fatty acids, and histone acetylation. In this mini-review, the relationship between fecal microbiota transplantation and Alzheimer's disease was summarized. It is hoped that fecal microbiota transplantation would play a positive role in the prevention and treatment of Alzheimer's disease in the future.
Collapse
Affiliation(s)
- Wu Xiang
- Department of Rehabilitation, Beibei Traditional Chinese Medical Hospital, Chongqing, China
- Department of Rehabilitation Medicine, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
| | - Han Xiang
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China
| | - Junyu Wang
- Department of Rehabilitation Medicine, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
| | - Yiqin Jiang
- Department of Rehabilitation, Beibei Traditional Chinese Medical Hospital, Chongqing, China
| | - Chuanhui Pan
- Department of Rehabilitation, Beibei Traditional Chinese Medical Hospital, Chongqing, China
| | - Bingjin Ji
- Department of Rehabilitation, Beibei Traditional Chinese Medical Hospital, Chongqing, China
| | - Anren Zhang
- Department of Rehabilitation Medicine, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
| |
Collapse
|
41
|
Dogra S, Oneto C, Sherman A, Varughese R, Yuen A, Sherman I, Cohen A, Luo Y, Chen LA. Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for C. difficile Infections Across Academic and Private Clinical Settings. J Clin Gastroenterol 2023; 57:1024-1030. [PMID: 36227005 PMCID: PMC10102254 DOI: 10.1097/mcg.0000000000001778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 09/05/2022] [Indexed: 12/10/2022]
Abstract
PURPOSE Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care. METHODS Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health. RESULTS CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P <0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3 mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT. CONCLUSIONS In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.
Collapse
Affiliation(s)
- Siddhant Dogra
- Division of Gastroenterology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
| | - Caterina Oneto
- Manhattan Clinical Research, LLC, New York, New York, USA
| | - Alex Sherman
- Manhattan Clinical Research, LLC, New York, New York, USA
| | | | - Alexa Yuen
- Division of Gastroenterology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
| | - Isabel Sherman
- Manhattan Clinical Research, LLC, New York, New York, USA
| | - Avi Cohen
- Manhattan Clinical Research, LLC, New York, New York, USA
| | - Yuying Luo
- Division of Gastroenterology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
| | - Lea Ann Chen
- Division of Gastroenterology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
| |
Collapse
|
42
|
Boicean A, Birlutiu V, Ichim C, Brusnic O, Onișor DM. Fecal Microbiota Transplantation in Liver Cirrhosis. Biomedicines 2023; 11:2930. [PMID: 38001930 PMCID: PMC10668969 DOI: 10.3390/biomedicines11112930] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/25/2023] [Accepted: 10/26/2023] [Indexed: 11/26/2023] Open
Abstract
The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual's well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.
Collapse
Affiliation(s)
- Adrian Boicean
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (V.B.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Victoria Birlutiu
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (V.B.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Cristian Ichim
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (V.B.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Olga Brusnic
- Department of Gastroenterology, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mures, Romania
| | - Danusia Maria Onișor
- Department of Gastroenterology, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mures, Romania
| |
Collapse
|
43
|
Lopetuso LR, Laterza L, Petito V, Pecere S, Quaranta G, Del Chierico F, Puca P, Schiavoni E, Napolitano D, Poscia A, Ianiro G, Pugliese D, Putignani L, Sanguinetti M, Armuzzi A, Masucci L, Gasbarrini A, Cammarota G, Scaldaferri F. Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study. Microorganisms 2023; 11:2536. [PMID: 37894194 PMCID: PMC10609093 DOI: 10.3390/microorganisms11102536] [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: 08/02/2023] [Revised: 09/26/2023] [Accepted: 10/06/2023] [Indexed: 10/29/2023] Open
Abstract
The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via colonoscopy. A control population with the same baseline features receiving Infliximab treatment was enrolled. Adverse events and clinical, endoscopic, and microbial outcomes were investigated. Nineteen patients with mildly-to-moderately active UC were enrolled. Clinical response was obtained in six patients at week 2, in eight at week 6, and in nine at week 12. Clinical response was maintained in eight patients at week 24. Endoscopic remission at week 12 was reached in six patients. In the control population, 13/19 patients achieved clinical response at week 6, and 10/19 patients maintained clinical response after 6 months. Microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus, and Veillonella were higher in non-responders, while Parabacteroides, Bacteroides, Faecalibacterium, and Akkermansia were higher in responders at all timepoints. Serial FMT infusions appear to be feasible, safe, and effective in UC patients, with a potential role in inducing and maintaining clinical response. Specific bacteria predict the response to FMT.
Collapse
Affiliation(s)
- Loris Riccardo Lopetuso
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
- Department of Medicine and Ageing Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | - Lucrezia Laterza
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
| | - Valentina Petito
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (G.I.); (G.C.)
| | - Silvia Pecere
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
| | - Gianluca Quaranta
- Microbiology Unit, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (G.Q.); (M.S.); (L.M.)
| | - Federica Del Chierico
- Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00168 Rome, Italy;
| | - Pierluigi Puca
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (G.I.); (G.C.)
| | - Elisa Schiavoni
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
| | - Daniele Napolitano
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
| | - Andrea Poscia
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Roma, Italy;
- UOC ISP Prevention and Surveillance of Infectious and Chronic Diseases, Department of Prevention, Local Health Authority (ASUR-AV2), 60035 Jesi, Italy
| | - Gianluca Ianiro
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (G.I.); (G.C.)
- UOC di Gastroenterologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy
| | - Daniela Pugliese
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
| | - Lorenza Putignani
- Unit of Microbiomics and Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00168 Rome, Italy;
| | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (G.Q.); (M.S.); (L.M.)
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy;
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (G.Q.); (M.S.); (L.M.)
| | - Antonio Gasbarrini
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (G.I.); (G.C.)
| | - Giovanni Cammarota
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (G.I.); (G.C.)
- UOC di Gastroenterologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy
| | - Franco Scaldaferri
- IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, L. Go A. Gemelli 8, 00168 Rome, Italy; (L.R.L.); (L.L.); (V.P.); (S.P.); (P.P.); (E.S.); (D.N.); (D.P.); (A.G.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (G.I.); (G.C.)
| |
Collapse
|
44
|
Shao T, Hsu R, Hacein-Bey C, Zhang W, Gao L, Kurth MJ, Zhao H, Shuai Z, Leung PSC. The Evolving Landscape of Fecal Microbial Transplantation. Clin Rev Allergy Immunol 2023; 65:101-120. [PMID: 36757537 PMCID: PMC9909675 DOI: 10.1007/s12016-023-08958-0] [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] [Accepted: 01/23/2023] [Indexed: 02/10/2023]
Abstract
The human gastrointestinal tract houses an enormous microbial ecosystem. Recent studies have shown that the gut microbiota plays significant physiological roles and maintains immune homeostasis in the human body. Dysbiosis, an imbalanced gut microbiome, can be associated with various disease states, as observed in infectious diseases, inflammatory diseases, autoimmune diseases, and cancer. Modulation of the gut microbiome has become a therapeutic target in treating these disorders. Fecal microbiota transplantation (FMT) from a healthy donor restores the normal gut microbiota homeostasis in the diseased host. Ample evidence has demonstrated the efficacy of FMT in recurrent Clostridioides difficile infection (rCDI). The application of FMT in other human diseases is gaining attention. This review aims to increase our understanding of the mechanisms of FMT and its efficacies in human diseases. We discuss the application, route of administration, limitations, safety, efficacies, and suggested mechanisms of FMT in rCDI, autoimmune diseases, and cancer. Finally, we address the future perspectives of FMT in human medicine.
Collapse
Affiliation(s)
- Tihong Shao
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
- Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, CA, 95616, USA
| | - Ronald Hsu
- Division of Gastroenterology, University of California Davis School of Medicine, Davis, CA, 95616, USA
| | - Camelia Hacein-Bey
- Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, CA, 95616, USA
| | - Weici Zhang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Lixia Gao
- Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Mark J Kurth
- Department of Chemistry, University of California Davis, Davis, CA, 95616, USA
| | - Huanhuan Zhao
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Zongwen Shuai
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Patrick S C Leung
- Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, CA, 95616, USA.
| |
Collapse
|
45
|
Poto R, Laniro G, de Paulis A, Spadaro G, Marone G, Gasbarrini A, Varricchi G. Is there a role for microbiome-based approach in common variable immunodeficiency? Clin Exp Med 2023; 23:1981-1998. [PMID: 36737487 PMCID: PMC9897624 DOI: 10.1007/s10238-023-01006-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 01/18/2023] [Indexed: 02/05/2023]
Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.
Collapse
Affiliation(s)
- Remo Poto
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy
- Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità (ISS), Rome, Italy
| | - Gianluca Laniro
- Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University of Rome, Rome, Italy
| | - Amato de Paulis
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy
| | - Giuseppe Spadaro
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy
| | - Gianni Marone
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131, Naples, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University of Rome, Rome, Italy
| | - Gilda Varricchi
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy.
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy.
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy.
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131, Naples, Italy.
| |
Collapse
|
46
|
Jess AT, Eskander GH, Vu MH, Michail S. Short-Chain Fatty Acid Levels after Fecal Microbiota Transplantation in a Pediatric Cohort with Recurrent Clostridioides difficile Infection. Metabolites 2023; 13:1039. [PMID: 37887364 PMCID: PMC10608736 DOI: 10.3390/metabo13101039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/19/2023] [Accepted: 09/22/2023] [Indexed: 10/28/2023] Open
Abstract
Though antibiotics are the mainstay treatment for Clostridioides difficile, a large population of individuals infected will experience recurrence. In turn, fecal microbiota transplantation (FMT) has emerged as a promising treatment for recurrent C. difficile infection (rCDI). Mechanistically, by providing a healthy, diverse flora to the infected individual, FMT "resets" the underlying gut microbiome dysbiosis associated with rCDI. A proposed mechanism through which this occurs is via microbiome metabolites such as short-chain fatty acids (SCFAs); however, this has not been previously studied in pediatric patients. Using mass spectroscopy, we quantified pre- and post-transplant levels of acetate, isovalerate, butyrate, formate, and propionate in pediatric patients diagnosed with rCDI (n = 9). We compared pre- and post-transplant levels within the rCDI cohort at 1, 3, 6, and 12 months post-transplant and correlated these levels with healthy controls (n = 19). We witnessed a significant difference in the combined SCFA levels and the individual levels of acetate, butyrate, isovalerate, and propionate in the pre-treatment rCDI cohort compared to the healthy controls. In addition, there was a significant increase in combined SCFA levels at 12 months post-transplant within the rCDI group compared to that of their pre-transplant levels, and, more specifically, acetate, propionate, and isovalerate increased from pre-transplant to 12 months post-transplant. The longitudinal aspect of this study allowed us to identify mechanisms that contribute to the durability of responses to FMT, as well as characterize the unique patterns of short-chain fatty acid level recovery in rCDI pediatric patients.
Collapse
Affiliation(s)
- Alison T. Jess
- Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA;
| | - George Hany Eskander
- School of Medicine & Health Sciences, George Washington University, Washington, DC 20052, USA;
| | - My H. Vu
- Biostatistics Core, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA;
| | - Sonia Michail
- Division of Gastroenterology, Children’s Hospital of Los Angeles, Los Angeles, CA 90027, USA
| |
Collapse
|
47
|
Gnatzy L, Ismailos G, Vertzoni M, Reppas C. Managing the clinical effects of drug-induced intestinal dysbiosis with a focus to antibiotics: Challenges and opportunities. Eur J Pharm Sci 2023; 188:106510. [PMID: 37380062 DOI: 10.1016/j.ejps.2023.106510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 06/23/2023] [Accepted: 06/26/2023] [Indexed: 06/30/2023]
Abstract
The term "intestinal dysbiosis" is used for indicating change(s) of the intestinal microbiota which have been associated with the development of diseases and the deterioration of disease treatments in humans. In this review, documented clinical effects of drug-induced intestinal dysbiosis are briefly presented, and methodologies which could be considered for the management of drug-induced intestinal dysbiosis based on clinical data are critically reviewed. Until relevant methodologies are optimized and/or their effectiveness to the general population is confirmed, and, since drug-induced intestinal dysbiosis refers predominantly to antibiotic-specific intestinal dysbiosis, a pharmacokinetically-based approach for mitigating the impact of antimicrobial therapy on intestinal dysbiosis is proposed.
Collapse
Affiliation(s)
- Lea Gnatzy
- Department of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece
| | - George Ismailos
- Experimental, Research and Training Center ELPEN, ELPEN Pharmaceuticals, Pikermi, Greece; National Antimicrobial Testing Committee, Athens, Greece
| | - Maria Vertzoni
- Department of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece
| | - Christos Reppas
- Department of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
| |
Collapse
|
48
|
Lopetuso LR, Deleu S, Godny L, Petito V, Puca P, Facciotti F, Sokol H, Ianiro G, Masucci L, Abreu M, Dotan I, Costello SP, Hart A, Iqbal TH, Paramsothy S, Sanguinetti M, Danese S, Tilg H, Cominelli F, Pizarro TT, Armuzzi A, Cammarota G, Gasbarrini A, Vermeire S, Scaldaferri F. The first international Rome consensus conference on gut microbiota and faecal microbiota transplantation in inflammatory bowel disease. Gut 2023; 72:1642-1650. [PMID: 37339849 PMCID: PMC10423477 DOI: 10.1136/gutjnl-2023-329948] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/16/2023] [Indexed: 06/22/2023]
Abstract
BACKGROUND Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors. OBJECTIVE To develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices. DESIGN An international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines. RESULTS AND CONCLUSIONS Our group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD.
Collapse
Affiliation(s)
- Loris Riccardo Lopetuso
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Department of Medicine and Ageing Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
- Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
| | - Sara Deleu
- Department of Chronic Diseases & Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Lihi Godny
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Valentina Petito
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Pierluigi Puca
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Federica Facciotti
- Dipartimento di Biotecnologie e Bioscienze, University of Milan-Bicocca, Milano, Italy
| | - Harry Sokol
- INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, Sorbonne Universite, Paris, France
| | - Gianluca Ianiro
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Luca Masucci
- Department of Laboratory Sciences and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Maria Abreu
- Department of Medicine, Division of Gastroenterology, Crohn's and Colitis Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Samuel Paul Costello
- Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia
| | - Ailsa Hart
- IBD Unit, Saint Mark's Hospital, Harrow, UK
| | - Tariq H Iqbal
- Microbiome Treatment Center, University of Birmingham, Birmingham, UK
| | - Sudarshan Paramsothy
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Maurizio Sanguinetti
- Department of Laboratory Sciences and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
| | - Fabio Cominelli
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Theresa T Pizarro
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Alessandro Armuzzi
- Deparment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
| | - Giovanni Cammarota
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Antonio Gasbarrini
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Séverine Vermeire
- Department of Chronic Diseases & Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Franco Scaldaferri
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| |
Collapse
|
49
|
Iancu MA, Profir M, Roşu OA, Ionescu RF, Cretoiu SM, Gaspar BS. Revisiting the Intestinal Microbiome and Its Role in Diarrhea and Constipation. Microorganisms 2023; 11:2177. [PMID: 37764021 PMCID: PMC10538221 DOI: 10.3390/microorganisms11092177] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/24/2023] [Accepted: 08/25/2023] [Indexed: 09/29/2023] Open
Abstract
The gut microbiota represents a community of microorganisms (bacteria, fungi, archaea, viruses, and protozoa) that colonize the gut and are responsible for gut mucosal structural integrity and immune and metabolic homeostasis. The relationship between the gut microbiome and human health has been intensively researched in the past years. It is now widely recognized that gut microbial composition is highly responsible for the general health of the host. Among the diseases that have been linked to an altered gut microbial population are diarrheal illnesses and functional constipation. The capacity of probiotics to modulate the gut microbiome population, strengthen the intestinal barrier, and modulate the immune system together with their antioxidant properties have encouraged the research of probiotic therapy in many gastrointestinal afflictions. Dietary and lifestyle changes and the use of probiotics seem to play an important role in easing constipation and effectively alleviating diarrhea by suppressing the germs involved. This review aims to describe how probiotic bacteria and the use of specific strains could interfere and bring benefits as an associated treatment for diarrhea and constipation.
Collapse
Affiliation(s)
- Mihaela Adela Iancu
- Department of Family Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Monica Profir
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania; (M.P.); (O.A.R.)
| | - Oana Alexandra Roşu
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania; (M.P.); (O.A.R.)
| | - Ruxandra Florentina Ionescu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Cardiology I, “Dr. Carol Davila” Central Military Emergency Hospital, 010825 Bucharest, Romania
| | - Sanda Maria Cretoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Bogdan Severus Gaspar
- Surgery Clinic, Emergency Clinical Hospital, 014461 Bucharest, Romania;
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| |
Collapse
|
50
|
Rossier L, Matter C, Burri E, Galperine T, Hrúz P, Juillerat P, Schoepfer A, Vavricka SR, Zahnd N, Décosterd N, Seibold F. Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice. Swiss Med Wkly 2023; 153:40100. [PMID: 37769622 DOI: 10.57187/smw.2023.40100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023] Open
Abstract
INTRODUCTION Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT. METHODS A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre). RESULTS The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future.
Collapse
Affiliation(s)
- Laura Rossier
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Christoph Matter
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Emanuel Burri
- Department of Gastroenterology and Hepatology, University Medical Clinic, Baselland Canton Hospital, Liestal, Switzerland
| | - Tatiana Galperine
- Fecal microbiota transplantation center, Department of infectious disease, Lausanne University Hospital, Lausanne, Switzerland
| | - Petr Hrúz
- Clarunis, Department of Gastroenterology, St Clara hospital and University hospital Basel, Basel, Switzerland
| | - Pascal Juillerat
- GastroGeb - Gastroenterology practice and Crohn-colitis Center, Lausanne - Bulle, Switzerland
| | - Alain Schoepfer
- Department of Gastroenterology, Lausanne University Hospital, Lausanne, Switzerland
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Natalie Décosterd
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Frank Seibold
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| |
Collapse
|