|
1
|
Li MJ, Chen HM, Chen YL, Lai YH, Lai CY, Ruan JW, Chen JW, Tsai WH, Ko WC, Tsai PJ. Lactiplantibacillus plantarum GMNL-661 Ameliorates Clostridioides difficile Infection and Reconfigures Intestinal Microbiota in a Murine Model. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10556-9. [PMID: 40327311 DOI: 10.1007/s12602-025-10556-9] [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] [Accepted: 04/21/2025] [Indexed: 05/07/2025]
Abstract
Clostridioides difficile infection (CDI) is a significant global health threat, often resulting from antibiotic-induced disruption of the gut microbiota, which leads to severe gastrointestinal issues. Current treatments, such as vancomycin, are effective but can cause subsequent relapses, further microbiota disruption, and high treatment costs. Probiotics offer a promising microbiota-based therapeutic strategy. Following an in vitro screening for novel lactic acid bacterial (LAB) strains with strong anti-C. difficile ability and good tolerance to digestive challenges, Lactiplantibacillus plantarum GMNL-661 emerged as a potential solution to combat CDI. In a CDI mice model, the appropriate dose of GMNL-661 effectively alleviated CDI, which caused weight loss, gut inflammation, and mucin depletion. GMNL-661 alleviated CDI symptoms through increased gut barrier genes and downregulated IL-1 and IL-18. 16s rDNA analysis of mice stool from CDI and CDI supplemented with GMNL-661 showed distinct microbiota ecology. GMNL-661 dramatically affected the microbiome of CDI, increasing Lactobacillus spp. and Clostridium cluster XVIII while reducing Clostridium and Enterococcus species. Genome analysis of GMNL-661 revealed minimal safety concerns in antibiotic resistance and virulence genes, confirming that it is suitable for inclusion in the food chain. Antimicrobial peptide (AMP) prediction on GMNL-661 and 299v genome suggested a strong potential candidate for anti-CD antimicrobial peptides. These findings highlighted L. plantarum GMNL-661 as an effective and highly safe therapeutic agent against CDI in clinical.
Collapse
Affiliation(s)
- Meng-Jia Li
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hong-Ming Chen
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Yanshuei District Health Station, Tainan, Taiwan
| | - Yueh-Lin Chen
- EirGenix Inc./Research & Development/Cell Line Engineering, Taipei, Taiwan
| | - Yi-Hsin Lai
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Cheng-Yu Lai
- Inong Agriculture Company Limited, Tainan, Taiwan
| | - Jhen-Wei Ruan
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jenn-Wei Chen
- Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wan-Hua Tsai
- Research and Development Department, GenMont Biotech Incorporation, Tainan, Taiwan
| | - Wen-Chien Ko
- National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
- Department of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Pei-Jane Tsai
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| |
Collapse
|
|
2
|
Bednárik DS, Földvári-Nagy KC, Simon V, Rancz A, Gede N, Veres DS, Paraskevopoulos P, Schnabel T, Erőss B, Hegyi P, Lenti K, Földvári-Nagy L. Comparative effectiveness of different therapies for Clostridioides difficile infection in adults: a systematic review and network meta-analysis of randomized controlled trials. THE LANCET REGIONAL HEALTH. EUROPE 2025; 49:101151. [PMID: 39989875 PMCID: PMC11846439 DOI: 10.1016/j.lanepe.2024.101151] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 11/12/2024] [Accepted: 11/13/2024] [Indexed: 02/25/2025]
Abstract
Background Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, with substantial morbidity and mortality. CDI is a severe and growing problem with numerous treatment options. We evaluated the effectiveness of all therapies in recurrent and non-recurrent infections and their prevention. Methods This network meta-analysis and systematic review of randomized controlled trials (RCTs) compared all CDI therapies and preventions. We included RCTs published until 19 August 2024 and focused on adult population. We performed a systematic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Inclusion criteria were patients: adults (>16) treated against CDI; study type: randomized controlled trial; outcome: cure rate, recurrence or effectiveness of prevention. Any publication not meeting all criteria was considered to be ineligible and excluded. We applied random-effects meta-analysis using frequentist methods. We reported our main results as odds ratios (as a symmetric effect size measure, OR) with 95% confidence interval (95% CI). We used the Cochrane risk-of-bias tool to assess the risk of bias. Our study protocol was preregistered in PROSPERO (CRD42022371210). Findings We assessed 73 RCTs with 28 interventions, involving 27,959 patients (49.2% female) in five networks. Fecal microbiota transplantation (FMT) was the most effective treatment in terms of the cure rate overall (P-score: 0.9952) and in recurrent cases (P-score: 0.9836). In recurrent cases, fidaxomicin (P-score: 0.6734) showed significantly greater effectiveness than vancomycin (P-score: 0.3677) and tolevamer (P-score: 0.0365). For non-recurrent CDI treatments ridinilazole, fidaxomicin, FMT and nitazoxanide were equally effective. Ridinilazole (P-score: 0.7671) and fidaxomicin (P-score: 0.7627) emerged as the most effective in preventing recurrence. Probiotics were not effective in preventing CDI, since network meta-analyses did not show significant differences between probiotics and placebo. In probiotics' subgroups pairwise meta-analyses Lactobacillaceae proved to be significantly more effective in prevention than placebo. Oral and colonoscopic FMT administration methods were equally effective. The study-level aggregated risk of bias of the publications included ranged from low to high. We observed relevant heterogeneity among studies in therapeutic doses, treatment durations, and follow-up times. Interpretation The superiority of FMT in the treatment of CDI highlights the potential for increased use of FMT in clinical settings. Further research on optimizing FMT protocols and exploring its long-term safety and efficacy in larger samples is needed. Our findings suggest that the preventive use of probiotics might be questioned. Funding None.
Collapse
Affiliation(s)
- Dániel Steve Bednárik
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Heim Pál National Pediatric Institute, Budapest, Hungary
| | - Kincső Csepke Földvári-Nagy
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
- Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
| | - Viktor Simon
- Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
| | - Anett Rancz
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Noémi Gede
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Dániel Sándor Veres
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
| | | | - Tamás Schnabel
- Department of Gastroenterology, Skien Hospital, Telemark Hospital Trust, Skien, Norway
| | - Bálint Erőss
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, University of Pécs, Medical School, Pécs, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, University of Pécs, Medical School, Pécs, Hungary
| | - Katalin Lenti
- Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
| | - László Földvári-Nagy
- Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
| |
Collapse
|
|
3
|
Lam JC, Bourassa-Blanchette S. Ten Clinical Pearls in Microbiology: How Effective Collaboration Optimizes Patient Care. Am J Med 2024; 137:818-824. [PMID: 38782247 DOI: 10.1016/j.amjmed.2024.05.013] [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: 05/03/2024] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 05/25/2024]
Abstract
Medical microbiology laboratories play an essential role in patient care-appertaining to infectious diseases diagnostics and treatment, infection prevention, and antimicrobial stewardship. Collaboration between clinicians and the microbiology laboratory can promote and enhance the safety, quality, and efficiency of patient care. We review practical, evidence-informed core concepts to explicate how effective partnership between clinicians and the microbiology laboratory improves patient outcomes.
Collapse
Affiliation(s)
- John C Lam
- Division of Infectious Diseases, Department of Medicine, University of California Los Angeles, Los Angeles, CA.
| | - Samuel Bourassa-Blanchette
- Division of Infectious Diseases, Department of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada; Division of Microbiology, Department of Pathology and Laboratory Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| |
Collapse
|
|
4
|
Li W, Chen H, Tang J. Interplay between Bile Acids and Intestinal Microbiota: Regulatory Mechanisms and Therapeutic Potential for Infections. Pathogens 2024; 13:702. [PMID: 39204302 PMCID: PMC11356816 DOI: 10.3390/pathogens13080702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/30/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024] Open
Abstract
Bile acids (BAs) play a crucial role in the human body's defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolase (BSH) activity but they also directly combat infections. Building upon our research group's previous discoveries highlighting the role of BAs in combating infections, we have initiated an in-depth investigation into the interactions between BAs and intestinal microbiota. Leveraging the existing literature, we offer a comprehensive analysis of the relationships between BAs and 16 key microbiota. This investigation encompasses bacteria (e.g., Clostridioides difficile (C. difficile), Staphylococcus aureus (S. aureus), Escherichia coli, Enterococcus, Pseudomonas aeruginosa, Mycobacterium tuberculosis (M. tuberculosis), Bacteroides, Clostridium scindens (C. scindens), Streptococcus thermophilus, Clostridium butyricum (C. butyricum), and lactic acid bacteria), fungi (e.g., Candida albicans (C. albicans) and Saccharomyces boulardii), and viruses (e.g., coronavirus SARS-CoV-2, influenza virus, and norovirus). Our research found that Bacteroides, C. scindens, Streptococcus thermophilus, Saccharomyces boulardii, C. butyricum, and lactic acid bacteria can regulate the metabolism and function of BSHs and 7α-dehydroxylase. BSHs and 7α-dehydroxylase play crucial roles in the conversion of primary bile acid (PBA) to secondary bile acid (SBA). It is important to note that PBAs generally promote infections, while SBAs often exhibit distinct anti-infection roles. In the antimicrobial action of BAs, SBAs demonstrate antagonistic properties against a wide range of microbiota, with the exception of norovirus. Given the intricate interplay between BAs and intestinal microbiota, and their regulatory effects on infections, we assert that BAs hold significant potential as a novel approach for preventing and treating microbial infections.
Collapse
Affiliation(s)
| | - Hui Chen
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, 128 Ruili Road, Shanghai 200240, China;
| | - Jianguo Tang
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, 128 Ruili Road, Shanghai 200240, China;
| |
Collapse
|
|
5
|
Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, Todi SK, Mohan A, Hegde A, Jagiasi BG, Krishna B, Rodrigues C, Govil D, Pal D, Divatia JV, Sengar M, Gupta M, Desai M, Rungta N, Prayag PS, Bhattacharya PK, Samavedam S, Dixit SB, Sharma S, Bandopadhyay S, Kola VR, Deswal V, Mehta Y, Singh YP, Myatra SN. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024; 28:S104-S216. [PMID: 39234229 PMCID: PMC11369928 DOI: 10.5005/jp-journals-10071-24677] [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: 02/14/2024] [Accepted: 03/20/2024] [Indexed: 09/06/2024] Open
Abstract
How to cite this article: Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, et al. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024;28(S2):S104-S216.
Collapse
Affiliation(s)
- Gopi C Khilnani
- Department of Pulmonary, Critical Care and Sleep Medicine, PSRI Hospital, New Delhi, India
| | - Pawan Tiwari
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Saurabh Mittal
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Atul P Kulkarni
- Division of Critical Care Medicine, Department of Anaesthesia, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Dhruva Chaudhry
- Department of Pulmonary and Critical Care Medicine, University of Health Sciences, Rohtak, Haryana, India
| | - Kapil G Zirpe
- Department of Neuro Trauma Unit, Grant Medical Foundation, Pune, Maharashtra, India
| | - Subhash K Todi
- Department of Critical Care, AMRI Hospital, Kolkata, West Bengal, India
| | - Anant Mohan
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Ashit Hegde
- Department of Medicine & Critical Care, P D Hinduja National Hospital, Mumbai, India
| | - Bharat G Jagiasi
- Department of Critical Care, Kokilaben Dhirubhai Ambani Hospital, Navi Mumbai, Maharashtra, India
| | - Bhuvana Krishna
- Department of Critical Care Medicine, St John's Medical College and Hospital, Bengaluru, India
| | - Camila Rodrigues
- Department of Microbiology, P D Hinduja National Hospital, Mumbai, India
| | - Deepak Govil
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Divya Pal
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Jigeeshu V Divatia
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manju Sengar
- Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mansi Gupta
- Department of Pulmonary Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Mukesh Desai
- Department of Immunology, Pediatric Hematology and Oncology Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
| | - Narendra Rungta
- Department of Critical Care & Anaesthesiology, Rajasthan Hospital, Jaipur, India
| | - Parikshit S Prayag
- Department of Transplant Infectious Diseases, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
| | - Pradip K Bhattacharya
- Department of Critical Care Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India
| | - Srinivas Samavedam
- Department of Critical Care, Ramdev Rao Hospital, Hyderabad, Telangana, India
| | - Subhal B Dixit
- Department of Critical Care, Sanjeevan and MJM Hospital, Pune, Maharashtra, India
| | - Sudivya Sharma
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Susruta Bandopadhyay
- Department of Critical Care, AMRI Hospitals Salt Lake, Kolkata, West Bengal, India
| | - Venkat R Kola
- Department of Critical Care Medicine, Yashoda Hospitals, Hyderabad, Telangana, India
| | - Vikas Deswal
- Consultant, Infectious Diseases, Medanta - The Medicity, Gurugram, Haryana, India
| | - Yatin Mehta
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Yogendra P Singh
- Department of Critical Care, Max Super Speciality Hospital, Patparganj, New Delhi, India
| | - Sheila N Myatra
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| |
Collapse
|
|
6
|
Spigaglia P. Clostridioides difficile and Gut Microbiota: From Colonization to Infection and Treatment. Pathogens 2024; 13:646. [PMID: 39204246 PMCID: PMC11357127 DOI: 10.3390/pathogens13080646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 07/23/2024] [Accepted: 07/29/2024] [Indexed: 09/03/2024] Open
Abstract
Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from mild diarrhea to severe manifestations such as pseudomembranous colitis. Epidemiological changes in CDIs have been observed in the last two decades, with the emergence of highly virulent types and more numerous and severe CDI cases in the community. C. difficile interacts with the gut microbiota throughout its entire life cycle, and the C. difficile's role as colonizer or invader largely depends on alterations in the gut microbiota, which C. difficile itself can promote and maintain. The restoration of the gut microbiota to a healthy state is considered potentially effective for the prevention and treatment of CDI. Besides a fecal microbiota transplantation (FMT), many other approaches to re-establishing intestinal eubiosis are currently under investigation. This review aims to explore current data on C. difficile and gut microbiota changes in colonized individuals and infected patients with a consideration of the recent emergence of highly virulent C. difficile types, with an overview of the microbial interventions used to restore the human gut microbiota.
Collapse
Affiliation(s)
- Patrizia Spigaglia
- Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Roma, Italy
| |
Collapse
|
|
7
|
Fehily SR, Basnayake C, Wright EK, Yao CK, Godsell J, Gibson PR, Kamm MA. Probiotics: are they beneficial? Intern Med J 2024; 54:861-870. [PMID: 38717051 DOI: 10.1111/imj.16388] [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: 01/16/2024] [Accepted: 03/13/2024] [Indexed: 06/18/2024]
Abstract
There are wide-ranging probiotic choices in Australasia. We reviewed the efficacy of probiotics for the management of gastrointestinal (GI) conditions in adults and assessed relevance to clinical practice. The benefits of probiotics were inconsistent, with a strong consensus reached for only a few of the indications. As different species/strains and combinations differ in efficacy, results cannot be extrapolated from one to another. This review endorses specific probiotics for limited indications. Efficacy of most marketed probiotic formulations remains unstudied and unproven, warranting further research.
Collapse
Affiliation(s)
- Sasha R Fehily
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Chamara Basnayake
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - C K Yao
- Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia
| | - Jack Godsell
- Department of Clinical Immunology & Allergy, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| |
Collapse
|
|
8
|
Wang L, Cao Y, Lou E, Zhao X, Chen X. The role of gut fungi in Clostridioides difficile infection. Biomed J 2024; 47:100686. [PMID: 38086471 PMCID: PMC11220531 DOI: 10.1016/j.bj.2023.100686] [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: 09/22/2023] [Revised: 12/01/2023] [Accepted: 12/05/2023] [Indexed: 06/10/2024] Open
Abstract
Clostridioides difficile, the etiological agent of C. difficile infection (CDI), elicits a spectrum of diarrheal symptoms with varying severity and the potential to result in severe complications such as colonic perforation, pseudomembranous colitis, and toxic megacolon. The perturbation of gut microbiome, often triggered by antibiotic usage, represents the primary factor augmenting the risk of CDI. This underscores the significance of interactions between C. difficile and the microbiome in determining pathogen adaptability. In recent years, researchers have increasingly recognized the pivotal role played by intestinal microbiota in host health and its therapeutic potential as a target for medical interventions. While extensive evidence has been established regarding the involvement of gut bacteria in CDI, our understanding of symbiotic interactions between hosts and fungi within intestinal microbiota remains limited. Herein, we aim to comprehensively elucidate both composition and key characteristics of gut fungal communities that significantly contribute to CDI, thereby enhancing our comprehension from pharmacological and biomarker perspectives while exploring their prospective therapeutic applications for CDI.
Collapse
Affiliation(s)
- Lamei Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China; Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Yangchun Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China; Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
| | - Eddie Lou
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Xuanyin Zhao
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Xinhua Chen
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
| |
Collapse
|
|
9
|
Stallhofer J, Steube A, Katzer K, Stallmach A. Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection. Visc Med 2024; 40:82-91. [PMID: 38584858 PMCID: PMC10995962 DOI: 10.1159/000535851] [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: 08/31/2023] [Accepted: 12/14/2023] [Indexed: 04/09/2024] Open
Abstract
Background Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon. Summary Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI - antibiotic-induced dysbiosis - hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA™) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST™) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT. Key Messages FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.
Collapse
Affiliation(s)
| | - Arndt Steube
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Katrin Katzer
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| |
Collapse
|
|
10
|
Valdés-Varela L, Gueimonde M, Ruas-Madiedo P. Probiotics for Prevention and Treatment of Clostridium difficile Infection. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1435:101-116. [PMID: 38175473 DOI: 10.1007/978-3-031-42108-2_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Probiotics have been claimed as a valuable tool to restore the balance in the intestinal microbiota following a dysbiosis caused by, among other factors, antibiotic therapy. This perturbed environment could favor the overgrowth of Clostridium difficile, and in fact, the occurrence of C. difficile-associated infections (CDI) is increasing in recent years. In spite of the high number of probiotics able to in vitro inhibit the growth and/or toxicity of this pathogen, its application for treatment or prevention of CDI is still scarce since there are not enough well-defined clinical studies supporting efficacy. Only a few strains, such as Lactobacillus rhamnosus GG and Saccharomyces boulardii, have been studied in more extent. The increasing knowledge about the probiotic mechanisms of action against C. difficile, some of them reviewed here, makes promising the application of these live biotherapeutic agents against CDI. Nevertheless, more effort must be paid to standardize the clinical studies conducted to evaluate probiotic products, in combination with antibiotics, in order to select the best candidate for C. difficile infections.
Collapse
Affiliation(s)
- Lorena Valdés-Varela
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lacteos de Asturias - Consejo Superior de Investigaciones Cientıficas (IPLA-CSIC), Villaviciosa, Asturias, Spain
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lacteos de Asturias - Consejo Superior de Investigaciones Cientıficas (IPLA-CSIC), Villaviciosa, Asturias, Spain
| | - Patricia Ruas-Madiedo
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lacteos de Asturias - Consejo Superior de Investigaciones Cientıficas (IPLA-CSIC), Villaviciosa, Asturias, Spain.
| |
Collapse
|
|
11
|
Rahman MN, Barua N, Tin MC, Dharmaratne P, Wong SH, Ip M. The use of probiotics and prebiotics in decolonizing pathogenic bacteria from the gut; a systematic review and meta-analysis of clinical outcomes. Gut Microbes 2024; 16:2356279. [PMID: 38778521 PMCID: PMC11123511 DOI: 10.1080/19490976.2024.2356279] [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: 12/17/2023] [Accepted: 05/13/2024] [Indexed: 05/25/2024] Open
Abstract
Repeated exposure to antibiotics and changes in the diet and environment shift the gut microbial diversity and composition, making the host susceptible to pathogenic infection. The emergence and ongoing spread of AMR pathogens is a challenging public health issue. Recent evidence showed that probiotics and prebiotics may play a role in decolonizing drug-resistant pathogens by enhancing the colonization resistance in the gut. This review aims to analyze available evidence from human-controlled trials to determine the effect size of probiotic interventions in decolonizing AMR pathogenic bacteria from the gut. We further studied the effects of prebiotics in human and animal studies. PubMed, Embase, Web of Science, Scopus, and CINAHL were used to collect articles. The random-effects model meta-analysis was used to pool the data. GRADE Pro and Cochrane collaboration tools were used to assess the bias and quality of evidence. Out of 1395 citations, 29 RCTs were eligible, involving 2871 subjects who underwent either probiotics or placebo treatment to decolonize AMR pathogens. The persistence of pathogenic bacteria after treatment was 22%(probiotics) and 30.8%(placebo). The pooled odds ratio was 0.59(95% CI:0.43-0.81), favoring probiotics with moderate certainty (p = 0.0001) and low heterogeneity (I2 = 49.2%, p = 0.0001). The funnel plot showed no asymmetry in the study distribution (Kendall'sTau = -1.06, p = 0.445). In subgroup, C. difficile showed the highest decolonization (82.4%) in probiotics group. Lactobacillus-based probiotics and Saccharomyces boulardii decolonize 71% and 77% of pathogens effectively. The types of probiotics (p < 0.018) and pathogens (p < 0.02) significantly moderate the outcome of decolonization, whereas the dosages and regions of the studies were insignificant (p < 0.05). Prebiotics reduced the pathogens from 30% to 80% of initial challenges. Moderate certainty of evidence suggests that probiotics and prebiotics may decolonize pathogens through modulation of gut diversity. However, more clinical outcomes are required on particular strains to confirm the decolonization of the pathogens. Protocol registration: PROSPERO (ID = CRD42021276045).
Collapse
Affiliation(s)
- Md Nannur Rahman
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, N.T., Hong Kong (SAR), China
- Department of Food Technology and Nutritional Science, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh
| | - Nilakshi Barua
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, N.T., Hong Kong (SAR), China
| | - Martha C.F. Tin
- Faculty of Medical Sciences, University College of London, London, UK
| | - Priyanga Dharmaratne
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, N.T., Hong Kong (SAR), China
| | - Sunny H. Wong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Margaret Ip
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, N.T., Hong Kong (SAR), China
- Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China
- Centre for Gut Microbiota, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, N.T., Hong Kong (SAR), China
| |
Collapse
|
|
12
|
Alam MZ, Markantonis JE, Fallon JT. Host Immune Responses to Clostridioides difficile Infection and Potential Novel Therapeutic Approaches. Trop Med Infect Dis 2023; 8:506. [PMID: 38133438 PMCID: PMC10747268 DOI: 10.3390/tropicalmed8120506] [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: 10/30/2023] [Revised: 11/17/2023] [Accepted: 11/19/2023] [Indexed: 12/23/2023] Open
Abstract
Clostridioides difficile infection (CDI) is a leading nosocomial infection, posing a substantial public health challenge within the United States and globally. CDI typically occurs in hospitalized elderly patients who have been administered antibiotics; however, there has been a rise in the occurrence of CDI in the community among young adults who have not been exposed to antibiotics. C. difficile releases toxins, which damage large intestinal epithelium, leading to toxic megacolon, sepsis, and even death. Unfortunately, existing antibiotic therapies do not always prevent these consequences, with up to one-third of treated patients experiencing a recurrence of the infection. Host factors play a crucial role in the pathogenesis of CDI, and accumulating evidence shows that modulation of host immune responses may potentially alter the disease outcome. In this review, we provide an overview of our current knowledge regarding the role of innate and adaptive immune responses on CDI outcomes. Moreover, we present a summary of non-antibiotic microbiome-based therapies that can effectively influence host immune responses, along with immunization strategies that are intended to tackle both the treatment and prevention of CDI.
Collapse
Affiliation(s)
- Md Zahidul Alam
- Department of Pathology and Laboratory Medicine, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA; (J.E.M.); (J.T.F.)
| | | | | |
Collapse
|
|
13
|
McFarland LV, Goldstein EJC, Kullar R. Microbiome-Related and Infection Control Approaches to Primary and Secondary Prevention of Clostridioides difficile Infections. Microorganisms 2023; 11:1534. [PMID: 37375036 DOI: 10.3390/microorganisms11061534] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/30/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023] Open
Abstract
Clostridioides difficile infections (CDIs) have decreased in the past years, but since 2021, some hospitals have reported an increase in CDI rates. CDI remains a global concern and has been identified as an urgent threat to healthcare. Although multiple treatment options are available, prevention strategies are more limited. As CDI is an opportunistic infection that arises after the normally protective microbiome has been disrupted, preventive measures aimed at restoring the microbiome have been tested. Our aim is to update the present knowledge on these various preventive strategies published in the past five years (2018-2023) to guide clinicians and healthcare systems on how to best prevent CDI. A literature search was conducted using databases (PubMed, Google Scholar, and clinicaltrials.gov) for phase 2-3 clinical trials for the primary or secondary prevention of CDI and microbiome and probiotics. As the main factor for Clostridium difficile infections is the disruption of the normally protective intestinal microbiome, strategies aimed at restoring the microbiome seem most rational. Some strains of probiotics, the use of fecal microbial therapy, and live biotherapeutic products offer promise to fill this niche; although, more large randomized controlled trials are needed that document the shifts in the microbiome population.
Collapse
Affiliation(s)
| | | | - Ravina Kullar
- Expert Stewardship Inc., Newport Beach, CA 92663, USA
| |
Collapse
|
|
14
|
Mulero-Cerezo J, Tuñón-Molina A, Cano-Vicent A, Pérez-Colomer L, Martí M, Serrano-Aroca Á. Alcoholic and non-alcoholic rosé wines made with Saccharomyces cerevisiae var. boulardii probiotic yeast. Arch Microbiol 2023; 205:201. [PMID: 37081186 DOI: 10.1007/s00203-023-03534-8] [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: 12/13/2022] [Revised: 03/30/2023] [Accepted: 04/01/2023] [Indexed: 04/22/2023]
Abstract
The production of alcoholic and non-alcoholic rosé wines using Saccharomyces cerevisiae var. boulardii probiotic yeast is described in this study for the first time. Before and after fermentation and distillation, the volatile acidity, lactic, and malic acid levels were evaluated for S. cerevisiae var. boulardii. These contents were compared to those obtained with a standard S. cerevisiae EC-1118 yeast. We measured the levels of gluconic acid and free amino nitrogen in the musts. After fermentation and distillation, yeast viability was assessed as a function of time (0, 15 days, 3 months, and 6 months), both at ambient temperature (25 ± 0.5 °C) and refrigerator temperature (4 ± 0.5 °C). The outcomes revealed that the rosé wine made with S. cerevisiae var. boulardii had the same values and preliminary sensory characteristics as other commercial wines made with S. cerevisiae EC-1118. The S. cerevisiae var. boulardii yeast successfully survived the high alcohol level produced during fermentation and vacuum distillation. The study also revealed that this unique rosé wine retains its probiotic viability for at least 6 months when stored at room temperature or in the refrigerator, making it a suitable candidate for large-scale production where long storage intervals are required by both producers and consumers.
Collapse
Affiliation(s)
- Joaquín Mulero-Cerezo
- Viñas Familia Gil, Paraje de la Aragona, Carretera de Fuente Álamo, 30520, Jumilla, Murcia, Spain
| | - Alberto Tuñón-Molina
- Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Guillem de Castro 94, 46001, Valencia, Spain
| | - Alba Cano-Vicent
- Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Guillem de Castro 94, 46001, Valencia, Spain
| | - Lorena Pérez-Colomer
- Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Guillem de Castro 94, 46001, Valencia, Spain
| | - Miguel Martí
- Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Guillem de Castro 94, 46001, Valencia, Spain
| | - Ángel Serrano-Aroca
- Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Guillem de Castro 94, 46001, Valencia, Spain.
| |
Collapse
|
|
15
|
Youn HY, Kim HJ, Kim DH, Jang YS, Kim H, Seo KH. Gut microbiota modulation via short-term administration of potential probiotic kefir yeast Kluyveromyces marxianus A4 and A5 in BALB/c mice. Food Sci Biotechnol 2023; 32:589-598. [PMID: 36911334 PMCID: PMC9992467 DOI: 10.1007/s10068-023-01268-3] [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: 09/21/2022] [Revised: 01/19/2023] [Accepted: 01/26/2023] [Indexed: 02/16/2023] Open
Abstract
Kefir yeast, Kluyveromyces marxianus, has been evaluated for its potential probiotic properties-survivability, non-pathogenicity, and antioxidant and anti-microbial activities. However, host gut microbiota modulation of kefir yeasts remains unclear. Here, we compared kefir yeast strains K. marxianus A4 (Km A4) and K. marxianus A5 (Km A5) with Saccharomyces boulardii ATCC MYA-796 (Sb MYA-796) by investigating their adherence to colorectal adenocarcinoma (Caco-2) cells and gut microbiota modulation in BALB/c mice. The kefir yeast strains exhibited higher intestinal cell adhesion than Sb MYA-796 (p < 0.05). Bacteroidetes, Bacteroidales, and Bacteroides were more abundant in the 1 × 108 CFU/mL of Km A4 treatment group than in the control group (p < 0.05). Moreover, 1 × 108 CFU/mL of Km A5 increased Corynebacteriales and Corynebacterium compared to the 1 × 108 CFU/mL of Km A4 treatment group (p < 0.01). The results showed that Km A4 and Km A5 had good Caco-2 cell adhesion ability and modulated gut microbiota upon short-term administration in healthy mice. Supplementary Information The online version contains supplementary material available at 10.1007/s10068-023-01268-3.
Collapse
Affiliation(s)
- Hye-Young Youn
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| | - Hyeon-Jin Kim
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| | - Dong-Hyeon Kim
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| | - Yong-Seok Jang
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| | - Hyunsook Kim
- Department of Food & Nutrition, College of Human Ecology, Hanyang University, Seoul, 04763 Republic of Korea
| | - Kun-Ho Seo
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| |
Collapse
|
|
16
|
Alam MZ, Maslanka JR, Abt MC. Immunological consequences of microbiome-based therapeutics. Front Immunol 2023; 13:1046472. [PMID: 36713364 PMCID: PMC9878555 DOI: 10.3389/fimmu.2022.1046472] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 12/16/2022] [Indexed: 01/15/2023] Open
Abstract
The complex network of microscopic organisms living on and within humans, collectively referred to as the microbiome, produce wide array of biologically active molecules that shape our health. Disruption of the microbiome is associated with susceptibility to a range of diseases such as cancer, diabetes, allergy, obesity, and infection. A new series of next-generation microbiome-based therapies are being developed to treat these diseases by transplanting bacteria or bacterial-derived byproducts into a diseased individual to reset the recipient's microbiome and restore health. Microbiome transplantation therapy is still in its early stages of being a routine treatment option and, with a few notable exceptions, has had limited success in clinical trials. In this review, we highlight the successes and challenges of implementing these therapies to treat disease with a focus on interactions between the immune system and microbiome-based therapeutics. The immune activation status of the microbiome transplant recipient prior to transplantation has an important role in supporting bacterial engraftment. Following engraftment, microbiome transplant derived signals can modulate immune function to ameliorate disease. As novel microbiome-based therapeutics are developed, consideration of how the transplants will interact with the immune system will be a key factor in determining whether the microbiome-based transplant elicits its intended therapeutic effect.
Collapse
Affiliation(s)
| | | | - Michael C. Abt
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| |
Collapse
|
|
17
|
Knudsen MJS, Rubin IMC, Petersen AM. The Clinical Efficacy, Safety, and Tolerability of Vancomycin for the Treatment of Recurrent Clostridioides difficile Infection - A Systematic Review. Drug Healthc Patient Saf 2023; 15:63-71. [PMID: 36974197 PMCID: PMC10039659 DOI: 10.2147/dhps.s348501] [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: 11/08/2022] [Accepted: 03/11/2023] [Indexed: 03/29/2023] Open
Abstract
Introduction The aim of this systematic review of randomized clinical trials (RCTs) was to examine the efficacy, safety, and tolerability of vancomycin for treatment of recurrent Clostridioides difficile infection (rCDI). Methods The PubMed database was searched from inception to August 23, 2022. An initial screening was performed followed by a full-text evaluation of the papers. Inclusion criteria were RCTs investigating vancomycin for treatment of rCDI. Results A total of six studies and 269 patients were included in the review. Three studies used a fixed dose regimen of vancomycin, one study used pulse regimen, one study used a taper-and-pulse regimen, and one study used a taper-and-pulse regimen for the participants with two or more recurrences. The resolution of infection varied from 19% to 58.3% in five of six studies reporting this as an outcome. Four out of six studies reported new episodes of rCDI as an intervention outcome, in those studies 50-63% of participants experienced rCDI. Regarding the safety and tolerability of vancomycin treatment for rCDI, one study described several adverse events regarding gastrointestinal discomfort along with fatigue and skin rash. There were no records of serious adverse events in the included studies. Conclusion While oral vancomycin is mostly safe and well tolerated in the RCTs reviewed here, the efficacy for treating rCDI varies greatly from 19-58.3%, and 50-63% of participants experienced new episodes of rCDI.
Collapse
Affiliation(s)
- Maja Johanne Søndergaard Knudsen
- Department of Clinical Microbiology, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
- Correspondence: Maja Johanne Søndergaard Knudsen, Email
| | - Ingrid Maria Cecilia Rubin
- Department of Clinical Microbiology, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
| | - Andreas Munk Petersen
- Department of Clinical Microbiology, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
- Department of Gastroenterology, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| |
Collapse
|
|
18
|
Bishop EJ, Tiruvoipati R. Management of Clostridioides difficile infection in adults and challenges in clinical practice: review and comparison of current IDSA/SHEA, ESCMID and ASID guidelines. J Antimicrob Chemother 2022; 78:21-30. [PMID: 36441203 PMCID: PMC9780550 DOI: 10.1093/jac/dkac404] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Clostridioides difficile infection (CDI) remains a significant clinical challenge both in the management of severe and severe-complicated disease and the prevention of recurrence. Guidelines released by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America (IDSA/SHEA) and ESCMID had some consensus as well as some discrepancies in disease severity classification and treatment recommendations. We review and compare the key clinical strategies from updated IDSA/SHEA, ESCMID and current Australasian guidelines for CDI management in adults and discuss relevant issues for clinicians, particularly in the management of severe-complicated infection. Updated IDSA/SHEA and ESCMID guidelines now reflect the increased efficacy of fidaxomicin in preventing recurrence and have both promoted fidaxomicin to first-line therapy with an initial CDI episode in both non-severe and severe disease and endorsed the role of bezlotoxumab in the prevention of recurrent infection. Vancomycin remains acceptable therapy and metronidazole is not preferred. For severe-complicated infection the IDSA/SHEA recommends high-dose oral ± rectal vancomycin and IV metronidazole, whilst in an important development, ESCMID has endorsed fidaxomicin and tigecycline as part of combination anti-CDI therapy, for the first time. The role of faecal microbiota transplantation (FMT) in second CDI recurrence is now clearer, but timing and mode of FMT in severe-complicated refractory disease still requires further study.
Collapse
Affiliation(s)
- Emma Jane Bishop
- Department of Infectious Diseases, Peninsula Health, Melbourne, Victoria, Australia
- Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Ravindranath Tiruvoipati
- Peninsula Clinical School, Monash University, Melbourne, Victoria, Australia
- Department of Intensive Care Medicine, Peninsula Health, Melbourne, Victoria, Australia
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| |
Collapse
|
|
19
|
Kim J, Cheong YE, Yu S, Jin YS, Kim KH. Strain engineering and metabolic flux analysis of a probiotic yeast Saccharomyces boulardii for metabolizing L-fucose, a mammalian mucin component. Microb Cell Fact 2022; 21:204. [PMID: 36207743 PMCID: PMC9541068 DOI: 10.1186/s12934-022-01926-x] [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: 08/08/2022] [Accepted: 09/19/2022] [Indexed: 11/24/2022] Open
Abstract
Background Saccharomyces boulardii is a probiotic yeast that exhibits antimicrobial and anti-toxin activities. Although S. boulardii has been clinically used for decades to treat gastrointestinal disorders, several studies have reported weak or no beneficial effects of S. boulardii administration in some cases. These conflicting results of S. boulardii efficacity may be due to nutrient deficiencies in the intestine that make it difficult for S. boulardii to maintain its metabolic activity. Results To enable S. boulardii to overcome any nutritional deficiencies in the intestine, we constructed a S. boulardii strain that could metabolize l-fucose, a major component of mucin in the gut epithelium. The fucU, fucI, fucK, and fucA from Escherichia coli and HXT4 from S. cerevisiae were overexpressed in S. boulardii. The engineered S. boulardii metabolized l-fucose and produced 1,2-propanediol under aerobic and anaerobic conditions. It also produced large amounts of 1,2-propanediol under strict anaerobic conditions. An in silico genome-scale metabolic model analysis was performed to simulate the growth of S. boulardii on l-fucose, and elementary flux modes were calculated to identify critical metabolic reactions for assimilating l-fucose. As a result, we found that the engineered S. boulardii consumes l-fucose via (S)-lactaldehyde-(S)-lactate-pyruvate pathway, which is highly oxygen dependent. Conclusion To the best of our knowledge, this is the first study in which S. cerevisiae and S. boulardii strains capable of metabolizing l-fucose have been constructed. This strategy could be used to enhance the metabolic activity of S. boulardii and other probiotic microorganisms in the gut. Supplementary Information The online version contains supplementary material available at 10.1186/s12934-022-01926-x.
Collapse
Affiliation(s)
- Jungyeon Kim
- Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.,Department of Biotechnology, Graduate School, Korea University, Seoul, 02841, Republic of Korea
| | - Yu Eun Cheong
- Department of Biotechnology, Graduate School, Korea University, Seoul, 02841, Republic of Korea
| | - Sora Yu
- Department of Biotechnology, Graduate School, Korea University, Seoul, 02841, Republic of Korea
| | - Yong-Su Jin
- Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. .,Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
| | - Kyoung Heon Kim
- Department of Biotechnology, Graduate School, Korea University, Seoul, 02841, Republic of Korea. .,Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
| |
Collapse
|
|
20
|
Kunishima H, Ohge H, Suzuki H, Nakamura A, Matsumoto K, Mikamo H, Mori N, Morinaga Y, Yanagihara K, Yamagishi Y, Yoshizawa S. Japanese Clinical Practice Guidelines for Management of Clostridioides (Clostridium) difficile infection. J Infect Chemother 2022; 28:1045-1083. [PMID: 35618618 DOI: 10.1016/j.jiac.2021.12.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/16/2021] [Accepted: 12/13/2021] [Indexed: 12/19/2022]
Affiliation(s)
- Hiroyuki Kunishima
- Department of Infectious Diseases, St. Marianna University School of Medicine, Japan.
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Japan
| | - Hiromichi Suzuki
- Division of Infectious Diseases, Department of Medicine, Tsukuba Medical Center Hospital, Japan
| | - Atsushi Nakamura
- Division of Infection Control and Prevention, Nagoya City University Hospital, Japan
| | - Kazuaki Matsumoto
- Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, Japan
| | - Hiroshige Mikamo
- Clinical Infectious Diseases, Graduate School of Medicine, Aichi Medical University, Japan
| | - Nobuaki Mori
- Division of General Internal Medicine and Infectious Diseases, National Hospital Organization Tokyo Medical Center, Japan
| | - Yoshitomo Morinaga
- Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Yuka Yamagishi
- Clinical Infectious Diseases, Graduate School of Medicine, Aichi Medical University, Japan
| | - Sadako Yoshizawa
- Department of Clinical Laboratory/Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Japan
| |
Collapse
|
|
21
|
Boeriu A, Roman A, Fofiu C, Dobru D. The Current Knowledge on Clostridioides difficile Infection in Patients with Inflammatory Bowel Diseases. Pathogens 2022; 11:819. [PMID: 35890064 PMCID: PMC9323231 DOI: 10.3390/pathogens11070819] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/17/2022] [Accepted: 07/18/2022] [Indexed: 11/17/2022] Open
Abstract
Clostridioides difficile (C. difficile) represents a major health burden with substantial economic and clinical impact. Patients with inflammatory bowel diseases (IBD) were identified as a risk category for Clostridioides difficile infection (CDI). In addition to traditional risk factors for C. difficile acquisition, IBD-specific risk factors such as immunosuppression, severity and extension of the inflammatory disease were identified. C. difficile virulence factors, represented by both toxins A and B, induce the damage of the intestinal mucosa and vascular changes, and promote the inflammatory host response. Given the potential life-threatening complications, early diagnostic and therapeutic interventions are required. The screening for CDI is recommended in IBD exacerbations, and the diagnostic algorithm consists of clinical evaluation, enzyme immunoassays (EIAs) or nucleic acid amplification tests (NAATs). An increased length of hospitalization, increased colectomy rate and mortality are the consequences of concurrent CDI in IBD patients. Selection of CD strains of higher virulence, antibiotic resistance, and the increasing rate of recurrent infections make the management of CDI in IBD more challenging. An individualized therapeutic approach is recommended to control CDI as well as IBD flare. Novel therapeutic strategies have been developed in recent years in order to manage severe, refractory or recurrent CDI. In this article, we aim to review the current evidence in the field of CDI in patients with underlying IBD, pointing to pathogenic mechanisms, risk factors for infection, diagnostic steps, clinical impact and outcomes, and specific management.
Collapse
Affiliation(s)
- Alina Boeriu
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania; (A.B.); (C.F.); (D.D.)
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| | - Adina Roman
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania; (A.B.); (C.F.); (D.D.)
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| | - Crina Fofiu
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania; (A.B.); (C.F.); (D.D.)
| | - Daniela Dobru
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania; (A.B.); (C.F.); (D.D.)
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| |
Collapse
|
|
22
|
High-Dose Vancomycin in the Treatment of Clostridioides difficile Infection. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2022. [DOI: 10.1097/ipc.0000000000001135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
|
|
23
|
Lacotte PA, Simons A, Bouttier S, Malet-Villemagne J, Nicolas V, Janoir C. Inhibition of In Vitro Clostridioides difficile Biofilm Formation by the Probiotic Yeast Saccharomyces boulardii CNCM I-745 through Modification of the Extracellular Matrix Composition. Microorganisms 2022; 10:microorganisms10061082. [PMID: 35744599 PMCID: PMC9227484 DOI: 10.3390/microorganisms10061082] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/21/2022] [Accepted: 05/21/2022] [Indexed: 12/14/2022] Open
Abstract
Clostridioides difficile is responsible for post-antibiotic diarrhea and most of the pseudomembranous colitis cases. Multiple recurrences, one of the major challenges faced in C. difficile infection (CDI) management, can be considered as chronic infections, and the role of biofilm formation in CDI recurrences is now widely considered. Therefore, we explored if the probiotic yeast Saccharomyces boulardii CNCM I-745 could impact the in vitro formation of C. difficile biofilm. Biomass staining and viable bacterial cell quantification showed that live S. boulardii exerts an antagonistic effect on the biofilm formation for the three C. difficile strains tested. Confocal laser scanning microscopy observation revealed a weakening and an average thickness reduction of the biofilm structure when C. difficile is co-incubated with S. boulardii, compared to the single-species bacterial biofilm structure. These effects, that were not detected with another genetically close yeast, S. cerevisiae, seemed to require direct contact between the probiotic yeast and the bacterium. Quantification of the extrapolymeric matrix components, as well as results obtained after DNase treatment, revealed a significant decrease of eDNA, an essential structural component of the C. difficile biofilm matrix, in the dual-species biofilm. This modification could explain the reduced cohesion and robustness of C. difficile biofilms formed in the presence of S. boulardii CNCM I-745 and be involved in S. boulardii clinical preventive effect against CDI recurrences.
Collapse
Affiliation(s)
- Pierre-Alexandre Lacotte
- INRAE, Université Paris-Saclay, AgroParisTech, Micalis Institute, 92290 Châtenay-Malabry, France; (P.-A.L.); (A.S.); (S.B.); (J.M.-V.)
| | - Alexis Simons
- INRAE, Université Paris-Saclay, AgroParisTech, Micalis Institute, 92290 Châtenay-Malabry, France; (P.-A.L.); (A.S.); (S.B.); (J.M.-V.)
- Laboratoire Eau, Environnement et Systèmes Urbains (Leesu), Université Paris-Est Créteil, École des Ponts ParisTech, 94010 Créteil, France
| | - Sylvie Bouttier
- INRAE, Université Paris-Saclay, AgroParisTech, Micalis Institute, 92290 Châtenay-Malabry, France; (P.-A.L.); (A.S.); (S.B.); (J.M.-V.)
| | - Jeanne Malet-Villemagne
- INRAE, Université Paris-Saclay, AgroParisTech, Micalis Institute, 92290 Châtenay-Malabry, France; (P.-A.L.); (A.S.); (S.B.); (J.M.-V.)
| | - Valérie Nicolas
- Ingénierie et Plateformes au Service de l’Innovation (IPSIT), UMS IPSIT Université Paris-Saclay-US 31 INSERM-UAR 3679 CNRS, Plateforme d’Imagerie Cellulaire MIPSIT, 92290 Châtenay-Malabry, France;
| | - Claire Janoir
- INRAE, Université Paris-Saclay, AgroParisTech, Micalis Institute, 92290 Châtenay-Malabry, France; (P.-A.L.); (A.S.); (S.B.); (J.M.-V.)
- Correspondence:
| |
Collapse
|
|
24
|
Vasilescu IM, Chifiriuc MC, Pircalabioru GG, Filip R, Bolocan A, Lazăr V, Diţu LM, Bleotu C. Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults. Front Microbiol 2022; 12:651081. [PMID: 35126320 PMCID: PMC8810811 DOI: 10.3389/fmicb.2021.651081] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 12/15/2021] [Indexed: 12/11/2022] Open
Abstract
In this review, we focus on gut microbiota profiles in infants and adults colonized (CDC) or infected (CDI) with Clostridioides difficile. After a short update on CDI epidemiology and pathology, we present the gut dysbiosis profiles associated with CDI in adults and infants, as well as the role of dysbiosis in C. difficile spores germination and multiplication. Both molecular and culturomic studies agree on a significant decrease of gut microbiota diversity and resilience in CDI, depletion of Firmicutes, Bacteroidetes, and Actinobacteria phyla and a high abundance of Proteobacteria, associated with low butyrogenic and high lactic acid-bacteria levels. In symptomatic cases, microbiota deviations are associated with high levels of inflammatory markers, such as calprotectin. In infants, colonization with Bifidobacteria that trigger a local anti-inflammatory response and abundance of Ruminococcus, together with lack of receptors for clostridial toxins and immunological factors (e.g., C. difficile toxins neutralizing antibodies) might explain the lack of clinical symptoms. Gut dysbiosis amelioration through administration of “biotics” or non-toxigenic C. difficile preparations and fecal microbiota transplantation proved to be very useful for the management of CDI.
Collapse
Affiliation(s)
- Iulia-Magdalena Vasilescu
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
- INBI “Prof. Dr. Matei Balş” – National Institute for Infectious Diseases, Bucharest, Romania
| | - Mariana-Carmen Chifiriuc
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
- Research Institute of the University of Bucharest, Bucharest, Romania
- Academy of Romanian Scientists, Bucharest, Romania
- The Romanian Academy, Bucharest, Romania
- *Correspondence: Mariana-Carmen Chifiriuc,
| | | | - Roxana Filip
- Faculty of Medicine and Biological Sciences, Stefan cel Mare University of Suceava, Suceava, Romania
- Regional County Emergency Hospital, Suceava, Romania
| | - Alexandra Bolocan
- Department of General Surgery, University Emergency Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Veronica Lazăr
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Lia-Mara Diţu
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Coralia Bleotu
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
- Research Institute of the University of Bucharest, Bucharest, Romania
- Ştefan S. Nicolau Institute of Virology, Romanian Academy, Bucharest, Romania
| |
Collapse
|
|
25
|
Paschos P, Ioakim K, Malandris K, Koukoufiki A, Nayfeh T, Akriviadis E, Tsapas A, Bekiari E. Add-on interventions for the prevention of recurrent Clostridioides Difficile infection: A systematic review and network meta-analysis. Anaerobe 2021; 71:102441. [PMID: 34454094 DOI: 10.1016/j.anaerobe.2021.102441] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 08/10/2021] [Accepted: 08/24/2021] [Indexed: 01/01/2023]
Abstract
OBJECTIVES We aimed to assess the comparative efficacy and safety of adjunctive interventions for the prevention of Clostridioides difficile recurrence. METHODS We searched Medline, Embase, CENTRAL, and clinicaltrials.gov up to May 2021. We included randomized controlled trials comparing interventions added to antibiotic therapy for prevention of CDI recurrence, to placebo or each other. Efficacy outcomes were CDI and diarrhea recurrence. Safety outcomes included the incidence of any adverse event (AE), serious AEs, and discontinuation due to AEs. We performed random-effects network meta-analysis. We ranked interventions based on SUCRA (surface under the cumulative ranking curve) probabilities. We assessed confidence in estimates utilizing the CINeMA (Confidence in Network Meta-Analysis) framework. RESULTS Fifteen trials (3909 patients) assessed 9 interventions. Oligofructose (OR 0.17; 95% CI, 0.07 to 0.46), NTCD-M3 (OR 0.29; 95% CI, 0.12 to 0.68), rifaximin (OR 0.47; 95% CI, 0.24 to 0.93), RBX2660 (OR 0.47; 95% CI, 0.22 to 0.99), the combination bezlotoxumab/actoxumab (OR 0.47; 95% CI, 0.37 to 0.60), and bezlotoxumab (OR, 0.53; 95% CI, 0.42 to 0.68) were associated with lower incidence of CDI recurrence than placebo (moderate confidence). Oligofructose was ranked highest, however data for oligofructose were derived solely from one small trial. Probiotics, actoxumab and SER-109 were not superior to placebo (low confidence). Probiotics were not well tolerated (low confidence) and actoxumab showed high rates of serious AEs (moderate confidence). CONCLUSION Add-on treatment with oligofructose, NTCD-M3 spores, rifaximin, RBX2660, and bezlotoxumab likely reduces the risk of CDI. Evidence on probiotics and SER-109 are uncertain, thus adequately powered trials are warranted.
Collapse
Affiliation(s)
- Paschalis Paschos
- Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece; First Department of Internal Medicine, "Papageorgiou" Hospital, Thessaloniki, Greece
| | - Konstantinos Ioakim
- First Department of Internal Medicine, "Papageorgiou" Hospital, Thessaloniki, Greece.
| | - Konstantinos Malandris
- Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Argyro Koukoufiki
- Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Evangelos Akriviadis
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, "Ippokratio" Hospital, Thessaloniki, Greece
| | - Apostolos Tsapas
- Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece; Harris Manchester College, University of Oxford, Oxford, United Kingdom
| | - Eleni Bekiari
- Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece
| |
Collapse
|
|
26
|
Milner E, Stevens B, An M, Lam V, Ainsworth M, Dihle P, Stearns J, Dombrowski A, Rego D, Segars K. Utilizing Probiotics for the Prevention and Treatment of Gastrointestinal Diseases. Front Microbiol 2021; 12:689958. [PMID: 34434175 PMCID: PMC8381467 DOI: 10.3389/fmicb.2021.689958] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022] Open
Abstract
Probiotics are heavily advertised to promote a healthy gastrointestinal tract and boost the immune system. This review article summarizes the history and diversity of probiotics, outlines conventional in vitro assays and in vivo models, assesses the pharmacologic effects of probiotic and pharmaceutical co-administration, and the broad impact of clinical probiotic utilization for gastrointestinal disease indications.
Collapse
Affiliation(s)
- Erin Milner
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
- Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
| | - Benjamin Stevens
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Martino An
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Victoria Lam
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Michael Ainsworth
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Preston Dihle
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Jocelyn Stearns
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Andrew Dombrowski
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Daniel Rego
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Katharine Segars
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| |
Collapse
|
|
27
|
Ansari F, Alian Samakkhah S, Bahadori A, Jafari SM, Ziaee M, Khodayari MT, Pourjafar H. Health-promoting properties of Saccharomyces cerevisiae var. boulardii as a probiotic; characteristics, isolation, and applications in dairy products. Crit Rev Food Sci Nutr 2021; 63:457-485. [PMID: 34254862 DOI: 10.1080/10408398.2021.1949577] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Saccharomyces cerevisiae var. boulardii (S. boulardii) has been isolated from lychee (Litchi chinensis), mangosteen fruit, kombucha, and dairy products like kefir. Dairy products containing S. boulardii have been revealed to possess potential probiotic activities owing to their ability to produce organic acids, essential enzymes, vitamins, and other important metabolites such as vanillic acid, phenyl ethyl alcohol, and erythromycin. S. boulardii has a wide spectrum of anti-carcinogenic, antibacterial antiviral, and antioxidant activity, and is known to reduce serum cholesterol levels. However, this yeast has mainly been prescribed for prophylaxis treatment of gastrointestinal infectious diseases, and stimulating the immune system in a number of commercially available products. The present comprehensive review article reviews the properties of S. boulardii related to their use in fermented dairy foods as a probiotic microorganism or starter culture. Technical aspects regarding the integration of this yeast into the dairy foods matrix its health advantages, therapeutic functions, microencapsulation, and viability in harsh conditions, and safety aspects are highlighted.
Collapse
Affiliation(s)
- Fereshteh Ansari
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Tehran, Iran.,Research Center for Evidence-Based Medicine, Health Management and Safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.,Iranian EBM Centre: A Joanna Briggs Institute Affiliated Group
| | - Shohre Alian Samakkhah
- Department of Food Hygiene and Quality Control, Faculty of Veterinary of Medicine, Amol University of Special Modern Technology, Amol, Iran
| | - Ali Bahadori
- Department of Medical Microbiology, Sarab Faculty of Medical Sciences, Sarab, Iran
| | - Seyedeh Maedeh Jafari
- Department of Comparative Bioscience, Faculty of Veterinary Medicine, Tehran University, Tehran, Iran
| | - Mojtaba Ziaee
- Medicinal Plants Research Center, Maragheh University of Medical Sciences, Maragheh, Iran
| | | | - Hadi Pourjafar
- Alborz University of Medical Sciences, Dietary Supplements and Probiotic Research Center, Karaj, Iran.,Department of Food Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| |
Collapse
|
|
28
|
Chen K, Zhu Y, Zhang Y, Hamza T, Yu H, Saint Fleur A, Galen J, Yang Z, Feng H. A probiotic yeast-based immunotherapy against Clostridioides difficile infection. Sci Transl Med 2021; 12:12/567/eaax4905. [PMID: 33115949 DOI: 10.1126/scitranslmed.aax4905] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 02/12/2020] [Accepted: 10/07/2020] [Indexed: 12/12/2022]
Abstract
Antibiotic-resistant Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the colon and is responsible for more than 29,000 deaths in the United States each year. Hence, C. difficile infection (CDI) poses an urgent threat to public health. Antibody-mediated neutralization of TcdA and TcdB toxins, the major virulence factors of CDI, represents an effective strategy to combat the disease without invoking antibiotic resistance. However, current antitoxin approaches are mostly based on parenteral infusion of monoclonal antibodies that are costly, narrow spectrum, and not optimized against the intestinal disease. Here, we engineered probiotic Saccharomyces boulardii to constitutively secrete a single tetra-specific antibody that potently and broadly neutralized both toxins and demonstrated protection against primary and recurrent CDI in both prophylactic and therapeutic mouse models of disease. This yeast immunotherapy is orally administered, can be used concurrently with antibiotics, and may have potential as a prophylactic against CDI risk and as a therapeutic for patients with CDI.
Collapse
Affiliation(s)
- Kevin Chen
- Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA
| | - Yixuan Zhu
- Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Yongrong Zhang
- Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA
| | - Therwa Hamza
- Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA
| | - Hua Yu
- FZata Inc., Halethorpe, MD 21227, USA
| | - Ashley Saint Fleur
- Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA
| | - James Galen
- Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | | | - Hanping Feng
- Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
| |
Collapse
|
|
29
|
Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116:1124-1147. [PMID: 34003176 DOI: 10.14309/ajg.0000000000001278] [Citation(s) in RCA: 289] [Impact Index Per Article: 72.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 03/25/2021] [Indexed: 02/06/2023]
Abstract
Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.
Collapse
Affiliation(s)
- Colleen R Kelly
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Monika Fischer
- Division of Gastroenterology, Indiana University, Indianapolis, Indiana, USA
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kerry LaPlante
- Department of Pharmacy Practice, University of Rhode Island College of Pharmacy, Kingston, Rhode Island, USA
| | - David B Stewart
- Department of Surgery, University of Arizona Health Sciences, Tucson, Arizona, USA
| | - Berkeley N Limketkai
- Division of Digestive Diseases, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA
| | - Neil H Stollman
- Division of Gastroenterology, Alta Bates Summit Medical Center, East Bay Center for Digestive Health, Oakland, California, USA
| |
Collapse
|
|
30
|
Chiu CW, Tsai PJ, Lee CC, Ko WC, Hung YP. Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents. Pathogens 2021; 10:pathogens10060649. [PMID: 34073695 PMCID: PMC8225043 DOI: 10.3390/pathogens10060649] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/02/2021] [Accepted: 05/19/2021] [Indexed: 02/07/2023] Open
Abstract
Oral vancomycin and metronidazole, though they are the therapeutic choice for Clostridioides difficile infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to C. difficile after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing Lactobacillus species, Saccharomyces boulardii, or Clostridium butyricum have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future.
Collapse
Affiliation(s)
- Chun-Wei Chiu
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan 700, Taiwan;
| | - Pei-Jane Tsai
- Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Medical College, Tainan 704, Taiwan;
| | - Ching-Chi Lee
- Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan;
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
| | - Wen-Chien Ko
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
- Department of Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Correspondence: (W.-C.K.); (Y.-P.H.)
| | - Yuan-Pin Hung
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan 700, Taiwan;
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
- Department of Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Correspondence: (W.-C.K.); (Y.-P.H.)
| |
Collapse
|
|
31
|
Crossing Kingdoms: How the Mycobiota and Fungal-Bacterial Interactions Impact Host Health and Disease. Infect Immun 2021; 89:IAI.00648-20. [PMID: 33526565 PMCID: PMC8090948 DOI: 10.1128/iai.00648-20] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The term “microbiota” invokes images of mucosal surfaces densely populated with bacteria. These surfaces and the luminal compartments they form indeed predominantly harbor bacteria. The term “microbiota” invokes images of mucosal surfaces densely populated with bacteria. These surfaces and the luminal compartments they form indeed predominantly harbor bacteria. However, research from this past decade has started to complete the picture by focusing on important but largely neglected constituents of the microbiota: fungi, viruses, and archaea. The community of commensal fungi, also called the mycobiota, interacts with commensal bacteria and the host. It is thus not surprising that changes in the mycobiota have significant impact on host health and are associated with pathological conditions such as inflammatory bowel disease (IBD). In this review we will give an overview of why the mycobiota is an important research area and different mycobiota research tools. We will specifically focus on distinguishing transient and actively colonizing fungi of the oral and gut mycobiota and their roles in health and disease. In addition to correlative and observational studies, we will discuss mechanistic studies on specific cross-kingdom interactions of fungi, bacteria, and the host.
Collapse
|
|
32
|
Leo VV, Viswanath V, Deka P, Zothanpuia, Ramji DR, Pachuau L, Carrie W, Malvi Y, Singh G, Singh BP. Saccharomyces and Their Potential Applications in Food and Food Processing Industries. Fungal Biol 2021. [DOI: 10.1007/978-3-030-67561-5_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
33
|
Kelly VW, Liang BK, Sirk SJ. Living Therapeutics: The Next Frontier of Precision Medicine. ACS Synth Biol 2020; 9:3184-3201. [PMID: 33205966 DOI: 10.1021/acssynbio.0c00444] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Modern medicine has long studied the mechanism and impact of pathogenic microbes on human hosts, but has only recently shifted attention toward the complex and vital roles that commensal and probiotic microbes play in both health and dysbiosis. Fueled by an enhanced appreciation of the human-microbe holobiont, the past decade has yielded countless insights and established many new avenues of investigation in this area. In this review, we discuss advances, limitations, and emerging frontiers for microbes as agents of health maintenance, disease prevention, and cure. We highlight the flexibility of microbial therapeutics across disease states, with special consideration for the rational engineering of microbes toward precision medicine outcomes. As the field advances, we anticipate that tools of synthetic biology will be increasingly employed to engineer functional living therapeutics with the potential to address longstanding limitations of traditional drugs.
Collapse
Affiliation(s)
- Vince W. Kelly
- Department of Bioengineering, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
| | - Benjamin K. Liang
- Department of Bioengineering, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
| | - Shannon J. Sirk
- Department of Bioengineering, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
| |
Collapse
|
|
34
|
Gil-Rodríguez AM, Garcia-Gutierrez E. Antimicrobial mechanisms and applications of yeasts. ADVANCES IN APPLIED MICROBIOLOGY 2020; 114:37-72. [PMID: 33934852 DOI: 10.1016/bs.aambs.2020.11.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Yeasts and humans have had a close relationship for millenia. Yeast have been used for food production since the first human societies. Since then, alternative uses have been discovered. Nowadays, antibiotic resistance constitutes a pressing need worldwide. In order to overcome this threat, one of the most important strategies is the search for new antimicrobials in natural sources. Moreover, biopreservation based on natural sources has emerged as an alternative to more common chemical preservatives. Yeasts constitute an underexploited source of antagonistic activity against other microorganisms. Here, we compile a summary of the antagonistic activity of yeast origin against other yeast and other microorganisms, such as bacteria or parasites. We present the mechanisms of action used by yeasts to display these activities. We also provide applications of these antagonistic activities in food industry and agriculture, medicine and veterinary, where yeast promise to play a pivotal role in the near future.
Collapse
|
|
35
|
Abstract
Diarrhea is a fairly common problem among the elderly that has a higher morbidity and mortality compared with the general population. There are multiple reasons for diarrhea in the elderly that can be stratified by different mechanisms: infectious, osmotic, secretory, inflammatory, and malabsorptive. Oral hydration and dietary management are the basic management principles for all forms of diarrhea but specific treatment should address the root cause of diarrhea in order to improve outcomes.
Collapse
Affiliation(s)
- Enad Dawod
- Department of Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, 1305 York Avenue, 4th Floor, New York, NY 10021, USA
| | - Carl V Crawford
- Division of Gastroenterology, Weill Cornell Medicine, New York Presbyterian Hospital, 1305 York Avenue, 4th Floor, New York, NY 10021, USA.
| |
Collapse
|
|
36
|
Tan GSE, Tay HL, Tan SH, Lee TH, Ng TM, Lye DC. Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship. Adv Ther 2020; 37:4054-4067. [PMID: 32767183 PMCID: PMC7412295 DOI: 10.1007/s12325-020-01458-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Indexed: 02/07/2023]
Abstract
The human microbiome comprises a complex ecosystem of microbial communities that exist within the human body, the largest and most diverse of which are found within the human intestine. It has been increasingly implicated in human health and diseases, demonstrably playing a critical role in influencing host immune response, protection against pathogen overgrowth, biosynthesis, and metabolism. As our understanding of the links between the gut microbiota with host immunity and infectious diseases deepens, there is a greater need to incorporate methods of modulating it as a means of therapy or infection prevention in daily clinical practice. Traditional antimicrobial stewardship principles have been evaluated to assess their impact on the gut microbiota diversity and the consequent repercussions, taking into consideration antibiotic pharmacokinetic and pharmacodynamic properties. Novel strategies of selective digestive decontamination and fecal microbiota transplantation to regulate the gut microbiota have also been tested in different conditions with variable results. This review seeks to provide an overview of the available literature on the modulation of the gut microbiota and its implications for infection control and antimicrobial stewardship. With increased understanding, gut microbiota profiling through metataxonomic analysis may provide further insight into modulating microbial communities in the context of infection prevention and control.
Collapse
Affiliation(s)
- Glorijoy Shi En Tan
- National Centre for Infectious Diseases, Singapore, Singapore
- Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore
| | - Hui Lin Tay
- Department of Pharmacy, Tan Tock Seng Hospital, Singapore, Singapore
| | - Sock Hoon Tan
- Department of Pharmacy, Tan Tock Seng Hospital, Singapore, Singapore
| | - Tau Hong Lee
- National Centre for Infectious Diseases, Singapore, Singapore
- Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore
- Lee Kong Chian School of Medicine, Singapore, Singapore
- Yong Loo Lin School of Medicine, Singapore, Singapore
| | - Tat Ming Ng
- Department of Pharmacy, Tan Tock Seng Hospital, Singapore, Singapore
| | - David Chien Lye
- National Centre for Infectious Diseases, Singapore, Singapore.
- Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore.
- Lee Kong Chian School of Medicine, Singapore, Singapore.
- Yong Loo Lin School of Medicine, Singapore, Singapore.
| |
Collapse
|
|
37
|
Hernandez BG, Vinithakumari AA, Sponseller B, Tangudu C, Mooyottu S. Prevalence, Colonization, Epidemiology, and Public Health Significance of Clostridioides difficile in Companion Animals. Front Vet Sci 2020; 7:512551. [PMID: 33062657 PMCID: PMC7530174 DOI: 10.3389/fvets.2020.512551] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 08/14/2020] [Indexed: 12/13/2022] Open
Abstract
Clostridioides difficile, previously Clostrdium difficile, is a major cause of antibiotic-associated enteric disease in humans in hospital settings. Increased incidence of C. difficile infection (CDI) in community settings raises concerns over an alternative source of CDI for humans. The detection of genetically similar and toxigenic C. difficile isolates in companion animals, including asymptomatic pets, suggests the potential role of household pets as a source of community-associated CDI. The close association between companion animals and humans, in addition to the use of similar antibiotics in both species, could provide a selective advantage for the emergence of new C. difficile strains and thus increase the incidental transmission of CDI to humans. Therefore, screening household pets for C. difficile is becoming increasingly important from a public health standpoint and may become a part of routine testing in the future, for the benefit of susceptible or infected individuals within a household. In this review, we analyze available information on prevalence, pathophysiology, epidemiology, and molecular genetics of C. difficile infection, focusing on companion animals and evaluate the risk of pet-borne transmission of CDI as an emerging public health concern. Molecular epidemiological characterization of companion animal C. difficile strains could provide further insights into the interspecies transmission of CDI. The mosaic nature of C. difficile genomes and their susceptibility to horizontal gene transfer may facilitate the inter-mixing of genetic material, which could increase the possibility of the emergence of new community-associated CDI strains. However, detailed genome-wide characterization and comparative genome analysis are warranted to confirm this hypothesis.
Collapse
Affiliation(s)
- Belen G. Hernandez
- Department of Veterinary Pathology, Iowa State University, Ames, IA, United States
| | | | - Brett Sponseller
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, United States
| | - Chandra Tangudu
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, United States
| | - Shankumar Mooyottu
- Department of Veterinary Pathology, Iowa State University, Ames, IA, United States
| |
Collapse
|
|
38
|
Sarangi NK, Stalcup A, Keyes TE. The Impact of Membrane Composition and Co‐Drug Synergistic Effects on Vancomycin Association with Model Membranes from Electrochemical Impedance Spectroscopy. ChemElectroChem 2020. [DOI: 10.1002/celc.202000818] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Nirod Kumar Sarangi
- School of Chemical Sciences and National Centre for Sensor Research Dublin City University DCU Glasnevin Campus D09 W6Y4 Dublin 9 Ireland
| | - Apryll Stalcup
- School of Chemical Sciences and National Centre for Sensor Research Dublin City University DCU Glasnevin Campus D09 W6Y4 Dublin 9 Ireland
| | - Tia E. Keyes
- School of Chemical Sciences and National Centre for Sensor Research Dublin City University DCU Glasnevin Campus D09 W6Y4 Dublin 9 Ireland
| |
Collapse
|
|
39
|
Bader MS, Hawboldt J, Main C, Mertz D, Loeb M, Farrell A, Joyce J. Review of high dose vancomycin in the treatment of Clostridioides difficile infection. Infect Dis (Lond) 2020; 52:847-857. [PMID: 32744879 DOI: 10.1080/23744235.2020.1800080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
BACKGROUND Guidelines recommend oral vancomycin as first-line therapy for Clostridioides difficile infection. Guideline recommendations vary regarding dosing of vancomycin. Our aim was to summarize the current evidence on the efficacy and adverse effects of high dose oral and vancomycin retention enema (>500 mg/day) for the treatment of C. difficile infection. METHODS We searched clinical studies and major guidelines in the English language using MEDLINE, the Cochrane Library and Embase from 1985 until 15 April 2020. RESULTS No evidence supports the use of high dose oral vancomycin in the treatment of severe C. difficile infection. Weak evidence from observational studies supports the use of high dose oral vancomycin in addition to intravenous metronidazole and high dose vancomycin retention enema in fulminant C. difficile infection. Vancomycin retention enema can be used in severe C. difficile infection when oral administration is not possible, or in conditions when the oral formulation cannot reach the colon such as Hartman's pouch, ileostomies, or colon diversions. CONCLUSIONS The dosing schedules for oral vancomycin and vancomycin enemas are not clearly defined due to widely varying results in clinical studies. Large, comparative multicenter trials are urgently needed to define the role of high dose vancomycin in C. difficile infection.
Collapse
Affiliation(s)
- Mazen S Bader
- Faculty of Health Sciences, Department of Medicine, Division of Infectious Diseases, McMaster University, Hamilton, Canada.,Hamilton Health Sciences, Juravinski Hospital and Cancer Centre, Hamilton, Canada
| | - John Hawboldt
- Faculty of Medicine, School of Pharmacy, Memorial University of Newfoundland and Labrador, St John's, Canada
| | - Cheryl Main
- Departments of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
| | - Dominik Mertz
- Department of Medicine, Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.,Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Mark Loeb
- Department of Medicine, Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.,Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Alison Farrell
- Public Services Librarian HSL, Memorial University of Newfoundland, St John's, Canada
| | - Joanna Joyce
- Department of Medicine, Division of Infectious Diseases, Memorial University, St John's, Canada
| |
Collapse
|
|
40
|
Preidis GA, Weizman AV, Kashyap PC, Morgan RL. AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology 2020; 159:708-738.e4. [PMID: 32531292 PMCID: PMC8018518 DOI: 10.1053/j.gastro.2020.05.060] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Geoffrey A. Preidis
- Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
| | - Adam V. Weizman
- Division of Gastroenterology, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Purna C. Kashyap
- Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Rebecca L. Morgan
- Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| |
Collapse
|
|
41
|
Abstract
PURPOSE OF REVIEW Clostridioides difficile infection (CDI) is a significant burden on the health system, especially due to high recurrence rates. Since the beginning of the CDI epidemic in early 2000s, many strategies for combatting recurrence have been explored, with moderate success so far. This review will focus on the most recent developments in recurrent CDI prevention and treatment. RECENT FINDINGS There are two main mechanisms of CDI recurrence: alteration in microbiome and poor antibody response. Development of new antibiotics aims to minimize damage to the microbiome. Fecal transplant or other microbiome replacement therapies seek to replenish the missing elements in the microbiome. Fecal microbiota transplant is the most effective treatment for prevention of CDI recurrenceso far, but is difficult to standardize and regulate, leading to efforts to develop microbiome-derived therapeutics. A deficiency in developing antibodies to C. difficile toxins is another mechanism of recurrence. Active immunization using toxoid vaccines or passive immunization using mAbs address this aspect. SUMMARY There are promising new treatments for recurrent CDI in development. Fecal microbiota transplant remains the most effective therapy for multiply recurrent CDI. New antibiotics, microbiome-derived therapeutics, and immunologic therapies are in development.
Collapse
|
|
42
|
Bermejo Boixareu C, Tutor-Ureta P, Ramos Martínez A. [Updated review of Clostridium difficile infection in elderly]. Rev Esp Geriatr Gerontol 2020; 55:225-235. [PMID: 32423602 DOI: 10.1016/j.regg.2019.12.003] [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: 02/13/2019] [Revised: 12/10/2019] [Accepted: 12/19/2019] [Indexed: 06/11/2023]
Abstract
Clostridium difficile infection is the most common cause of health care-associated diarrhoea, and its incidence increases with age. Clinical challenges, risk of resistance to treatment, risk of recurrence, and treatment responses are different in elderly. The aim of this review is to discuss the updated epidemiology, pathophysiology, diagnosis, and therapeutic management of C. difficile infection in elderly with the available data.
Collapse
Affiliation(s)
| | - Pablo Tutor-Ureta
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España
| | - Antonio Ramos Martínez
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España
| |
Collapse
|
|
43
|
Wombwell E, Patterson ME, Bransteitter B, Gillen LR. The Effect of Saccharomyces boulardii Primary Prevention on Risk of Hospital-onset Clostridioides difficile Infection in Hospitalized Patients Administered Antibiotics Frequently Associated With C. difficile Infection. Clin Infect Dis 2020; 73:e2512-e2518. [DOI: 10.1093/cid/ciaa808] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 06/15/2020] [Indexed: 12/18/2022] Open
Abstract
Abstract
Background
Hospital-onset Clostridioides difficile infection (HO-CDI) is a costly problem leading to readmissions, morbidity, and mortality. We evaluated the effect of a single probiotic strain, Saccharomyces boulardii, at a standardized dose on the risk of HO-CDI within hospitalized patients administered antibiotics frequently associated with HO-CDI.
Methods
This retrospective cohort study merged hospital prescribing data with HO-CDI case data. The study assessed patients hospitalized from January 2016 through March 2017 who were administered at least 1 dose of an antibiotic frequently associated with HO-CDI during hospitalization. Associations between S. boulardii administration, including timing, and HO-CDI incidence were evaluated by multivariable logistic regression.
Results
The study included 8763 patients. HO-CDI incidence was 0.66% in the overall cohort. HO-CDI incidence was 0.56% and 0.82% among patients coadministered S. boulardii with antibiotics and not coadministered S. boulardii, respectively. In adjusted analysis, patients coadministered S. boulardii had a reduced risk of HO-CDI (odds ratio [OR], 0.57 [95% confidence interval {CI}, .33–.96]; P = .04) compared to patients not coadministered S. boulardii. Patients coadministered S. boulardii within 24 hours of antibiotic start demonstrated a reduced risk of HO-CDI (OR, 0.47 [95% CI, .23–.97]; P = .04) compared to those coadministered S. boulardii after 24 hours of antibiotic start.
Conclusions
Saccharomyces boulardii administered to hospitalized patients prescribed antibiotics frequently linked with HO-CDI was associated with a reduced risk of HO-CDI.
Collapse
Affiliation(s)
- Eric Wombwell
- Division of Pharmacy Practice and Administration, University of Missouri–Kansas City School of Pharmacy, Kansas City, Missouri, USA
- Department of Pharmacy, Centerpoint Medical Center, Independence, Missouri, USA
| | - Mark E Patterson
- Division of Pharmacy Practice and Administration, University of Missouri–Kansas City School of Pharmacy, Kansas City, Missouri, USA
| | | | - Lisa R Gillen
- Department of Pharmacy, Centerpoint Medical Center, Independence, Missouri, USA
| |
Collapse
|
|
44
|
Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases. Curr Microbiol 2020; 77:1987-1996. [PMID: 32472262 PMCID: PMC7415030 DOI: 10.1007/s00284-020-02053-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 05/23/2020] [Indexed: 02/07/2023]
Abstract
The yeast Saccharomyces boulardii CNCM I-745 is a unique, non-bacterial microorganism classified as a probiotic agent. In this review article, at first, we briefly summarized the mechanisms responsible for its probiotic properties, e.g. adhesion to and elimination of enteropathogenic microorganisms and their toxins; extracellular cleavage of pathogens’ virulent factors; trophic and anti-inflammatory effects on the intestinal mucosa. The efficacy of S. boulardii administration was tested in variety of human diseases. We discussed the results of S. boulardii CNCM I-745 use in the treatment or prevention of Helicobacter pylori infections, diarrhoea (Clostridium difficile infections, antibiotic-associated diarrhoea, and traveller’s diarrhoea), inflammatory bowel diseases, irritable bowel syndrome, candidiasis, dyslipidemia, and small intestine bacterial overgrowth in patients with multiple sclerosis. In case of limited number of studies regarding this strain, we also presented studies demonstrating properties and efficacy of other strains of S. boulardii. Administration of S. boulardii CNCMI I-745 during antibiotic therapy has certain advantage over bacterial probiotics, because—due to its fungal natural properties—it is intrinsically resistant to the antibiotics and cannot promote the spread of antimicrobial resistance. Even though cases of fungemia following S. boulardii CNCM I-745 administration were reported, it should be treated as a widely available and safe probiotic strain.
Collapse
|
|
45
|
Bundling Probiotics With Antimicrobial Stewardship Programs for the Prevention of Clostridiodes difficile Infections in Acute Care Hospitals. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2020. [DOI: 10.1097/ipc.0000000000000853] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
46
|
Frisbee AL, Petri WA. Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection. Trends Mol Med 2020; 26:496-507. [PMID: 32359480 PMCID: PMC7198612 DOI: 10.1016/j.molmed.2020.01.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 01/05/2020] [Accepted: 01/21/2020] [Indexed: 12/15/2022]
Abstract
Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of mucosal immunology and microbiology. This excitement is well founded, as demonstrated by 90% relapse-free cure rates in FMT treatment for recurrent Clostridioides difficile infections. Growing evidence suggests that in addition to bacterial factors, the host immune response during C. difficile infection greatly influences disease severity. In this review, we discuss recent advancements in understanding the interplay between immune cells and the microbiota and how they may relate to recovery from C. difficile through FMT therapy.
Collapse
Affiliation(s)
- Alyse L Frisbee
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
| | - William A Petri
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia Health System, Charlottesville, Virginia 22908, USA; Department of Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA; Department of Pathology, University of Virginia Health System, Charlottesville, Virginia 22908, USA
| |
Collapse
|
|
47
|
Mogilnicka I, Ufnal M. Gut Mycobiota and Fungal Metabolites in Human Homeostasis. Curr Drug Targets 2020; 20:232-240. [PMID: 30047327 DOI: 10.2174/1389450119666180724125020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 05/13/2018] [Accepted: 07/19/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Accumulating evidence suggests that microbiota play an important role in host's homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites. METHODS We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis. RESULTS Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases. CONCLUSION The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.
Collapse
Affiliation(s)
- Izabella Mogilnicka
- Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
| | - Marcin Ufnal
- Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
| |
Collapse
|
|
48
|
Horve PF, Lloyd S, Mhuireach GA, Dietz L, Fretz M, MacCrone G, Van Den Wymelenberg K, Ishaq SL. Building upon current knowledge and techniques of indoor microbiology to construct the next era of theory into microorganisms, health, and the built environment. JOURNAL OF EXPOSURE SCIENCE & ENVIRONMENTAL EPIDEMIOLOGY 2020; 30:219-235. [PMID: 31308484 PMCID: PMC7100162 DOI: 10.1038/s41370-019-0157-y] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 06/23/2019] [Accepted: 06/30/2019] [Indexed: 05/06/2023]
Abstract
In the constructed habitat in which we spend up to 90% of our time, architectural design influences occupants' behavioral patterns, interactions with objects, surfaces, rituals, the outside environment, and each other. Within this built environment, human behavior and building design contribute to the accrual and dispersal of microorganisms; it is a collection of fomites that transfer microorganisms; reservoirs that collect biomass; structures that induce human or air movement patterns; and space types that encourage proximity or isolation between humans whose personal microbial clouds disperse cells into buildings. There have been recent calls to incorporate building microbiology into occupant health and exposure research and standards, yet the built environment is largely viewed as a repository for microorganisms which are to be eliminated, instead of a habitat which is inexorably linked to the microbial influences of building inhabitants. Health sectors have re-evaluated the role of microorganisms in health, incorporating microorganisms into prevention and treatment protocols, yet no paradigm shift has occurred with respect to microbiology of the built environment, despite calls to do so. Technological and logistical constraints often preclude our ability to link health outcomes to indoor microbiology, yet sufficient study exists to inform the theory and implementation of the next era of research and intervention in the built environment. This review presents built environment characteristics in relation to human health and disease, explores some of the current experimental strategies and interventions which explore health in the built environment, and discusses an emerging model for fostering indoor microbiology rather than fearing it.
Collapse
Affiliation(s)
- Patrick F Horve
- Biology and the Built Environment Center, University of Oregon, Eugene, OR, 97403, USA
| | - Savanna Lloyd
- Biology and the Built Environment Center, University of Oregon, Eugene, OR, 97403, USA
| | - Gwynne A Mhuireach
- Biology and the Built Environment Center, University of Oregon, Eugene, OR, 97403, USA
| | - Leslie Dietz
- Biology and the Built Environment Center, University of Oregon, Eugene, OR, 97403, USA
| | - Mark Fretz
- Institute for Health and the Built Environment, University of Oregon, Portland, OR, 97209, USA
| | - Georgia MacCrone
- Biology and the Built Environment Center, University of Oregon, Eugene, OR, 97403, USA
| | - Kevin Van Den Wymelenberg
- Biology and the Built Environment Center, University of Oregon, Eugene, OR, 97403, USA
- Institute for Health and the Built Environment, University of Oregon, Portland, OR, 97209, USA
| | - Suzanne L Ishaq
- Biology and the Built Environment Center, University of Oregon, Eugene, OR, 97403, USA.
| |
Collapse
|
|
49
|
Moon JE, Heo W, Lee SH, Lee SH, Lee HG, Lee JH, Kim YJ. Trehalose Protects the Probiotic Yeast Saccharomyces boulardii against Oxidative Stress-Induced Cell Death. J Microbiol Biotechnol 2020; 30:54-61. [PMID: 31546305 PMCID: PMC9728326 DOI: 10.4014/jmb.1906.06041] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Saccharomyces boulardii is the only probiotic yeast with US Food and Drug Administration approval. It is routinely used to prevent or treat acute diarrhea and other gastrointestinal disorders, including the antibiotic-associated diarrhea caused by Clostridium difficile infections. The formation of reactive oxygen species (ROS), specifically H2O2 during normal aerobic metabolism, contributes to programmed cell death and represents a risk to the viability of the probiotic microbe. Moreover, a loss of viability reduces the efficacy of the probiotic treatment. Therefore, inhibiting the accumulation of ROS in the oxidant environment could improve the viability of the probiotic yeast and lead to more efficacious treatment. Here, we provide evidence that supplementation with a non-reducing disaccharide, namely trehalose, enhanced the viability of S. boulardii exposed to an oxidative environment by preventing metacaspase YCA1-mediated programmed cell death through inhibition of intracellular ROS production. Our results suggest that supplementation with S. boulardii together with trehalose could increase the viability of the organism, and thus improve its effectiveness as a probiotic and as a treatment for acute diarrhea and other gastrointestinal disorders.
Collapse
Affiliation(s)
- Ji Eun Moon
- Department of Food and Biotechnology, Korea University, Sejong 3009, Republic of Korea
| | - Wan Heo
- Institutes of Natural Sciences, Korea University, Sejong 30019, Republic of Korea
| | - Sang Hoon Lee
- Department of Food and Biotechnology, Korea University, Sejong 3009, Republic of Korea
| | - Suk Hee Lee
- Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Taegu 41566, Republic of Korea
| | - Hong Gu Lee
- Department of Animal Science and Technology, College of Animal Bioscience and Technology, Konkuk University, Seoul 05029, Republic of Korea
| | - Jin Hyup Lee
- Department of Food and Biotechnology, Korea University, Sejong 3009, Republic of Korea,Corresponding authors J.H.L. Phone: +82-44-860-1764 Fax: +82-44-860-1430 E-mail:
| | - Young Jun Kim
- Department of Food and Biotechnology, Korea University, Sejong 3009, Republic of Korea,Y.J.K. Phone: +82-44-860-1435 Fax: +82-44-860-1780 E-mail:
| |
Collapse
|
|
50
|
Elangovan A, Allegretti JR, Fischer M. Microbiota modulation-based therapy for luminal GI disorders: current applications of probiotics and fecal microbiota transplantation. Expert Opin Biol Ther 2019; 19:1343-1355. [PMID: 31570017 DOI: 10.1080/14712598.2019.1673725] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction: Alteration in the intestinal microbiota also termed as intestinal dysbiosis has been demonstrated in numerous gastrointestinal disorders linked to aberrant immune processes, acquisition of pathogenic organisms and often administration of antibiotics. Restoration of microbiota through probiotics and fecal microbiota transplantation (FMT) has gained tremendous popularity among researchers in the prevention and treatment of gastrointestinal diseases.Areas covered: In this review, studies testing the safety and efficacy of probiotics and FMT for the treatment of various infectious and inflammatory luminal gastrointestinal diseases are reviewed. Randomized control studies are given priority while important uncontrolled studies are also highlighted.Expert opinion: Probiotics have demonstrated efficacy in the prevention of antibiotic-associated diarrhea and in the eradication of Helicobacter pylori infection. Their utility in the primary and secondary prevention of Clostridioides difficile infection is debatable. The future of medicine should bring forth a personalized approach to probiotic use. FMT has revolutionized the treatment of recurrent CDI as well as severe and fulminant CDI. At the same time, it has galvanized gut microbiota research in the last decade. While FMT in ulcerative colitis appears promising, further studies on the durability and long-term safety are needed before it can be recommended in clinical practice.
Collapse
Affiliation(s)
- Abbinaya Elangovan
- Department of Medicine-Pediatrics, MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH, USA
| | - Jessica R Allegretti
- Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA
| | - Monika Fischer
- Medicine, Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| |
Collapse
|