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Lee ZY, Lew CCH, Ortiz-Reyes A, Patel JJ, Wong YJ, Loh CTI, Martindale RG, Heyland DK. Benefits and harm of probiotics and synbiotics in adult critically ill patients. A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. Clin Nutr 2023; 42:519-531. [PMID: 36857961 DOI: 10.1016/j.clnu.2023.01.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/08/2023] [Accepted: 01/28/2023] [Indexed: 02/10/2023]
Abstract
BACKGROUND & AIMS Several systematic reviews and meta-analyses of randomized controlled trials concluded that probiotics administration in critically ill patients was safe and associated with reduced rates of ventilator-associated pneumonia and diarrhea. However, a recent large multicenter trial found probiotics administration, compared to placebo, was not efficacious and increased adverse events. An updated meta-analysis that controls for type-1 and -2 errors using trial sequential analysis, with a detailed account of adverse events associated with probiotic administration, is warranted to confirm the safety and efficacy of probiotic use in critically ill patients. METHODS RCTs that compared probiotics or synbiotics to usual care or placebo and reported clinical and diarrheal outcomes were searched in 4 electronic databases from inception to March 8, 2022 without language restriction. Four reviewers independently extracted data and assessed the study qualities using the Critical Care Nutrition (CCN) Methodological Quality Scoring System. Random-effect meta-analysis and trial sequential analysis (TSA) were used to synthesize the results. The primary outcome was ventilator-associated pneumonia (VAP). The main subgroup analysis compared the effects of higher versus lower quality studies (based on median CCN score). RESULTS Seventy-five studies with 71 unique trials (n = 8551) were included. In the overall analysis, probiotics significantly reduced VAP incidence (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.56-0.88; I2 = 65%; 16 studies). However, such benefits were demonstrated only in lower (RR 0.47, 95% CI 0.32, 0.69; I2 = 44%; 7 studies) but not higher quality studies (RR 0.89, 95% CI 0.73, 1.08; I2 = 43%; 9 studies), with significant test for subgroup differences (p = 0.004). Additionally, TSA showed that the VAP benefits of probiotics in the overall and subgroup analyses were type-1 errors. In higher quality trials, TSA found that future trials are unlikely to demonstrate any benefits of probiotics on infectious complications and diarrhea. Probiotics had higher adverse events than control (pooled risk difference: 0.01, 95% CI 0.01, 0.02; I2 = 0%; 22 studies). CONCLUSION High-quality RCTs did not support a beneficial effect of probiotics on clinical or diarrheal outcomes in critically ill patients. Given the lack of benefits and the increased incidence of adverse events, probiotics should not be routinely administered to critically ill patients. PROSPERO REGISTRATION CRD42022302278.
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Affiliation(s)
- Zheng-Yii Lee
- Department of Anesthesiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
| | - Charles Chin Han Lew
- Department of Dietetics & Nutrition, Ng Teng Fong General Hospital, 1 Jurong East Street 21, Singapore 609606
| | - Alfonso Ortiz-Reyes
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, K1Y 4E9, Canada
| | - Jayshil J Patel
- Division of Pulmonary & Critical Care Medicine, Medical College of Wisconsin Milwaukee, Wisconsin, USA
| | - Yu Jun Wong
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore; Duke-NUS Medical School, Singapore
| | - Carolyn Tze Ing Loh
- Department of Anesthesiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | | | - Daren K Heyland
- Clinical Evaluation Research Unit, Department of Critical Care Medicine, Queen's University, Kingston, ON, K7L 3N6, Canada
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Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit Care Med 2022; 50:1175-1186. [PMID: 35608319 DOI: 10.1097/ccm.0000000000005580] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To determine the safety and efficacy of probiotics or synbiotics on morbidity and mortality in critically ill adults and children. DATA SOURCES We searched MEDLINE, EMBASE, CENTRAL, and unpublished sources from inception to May 4, 2021. STUDY SELECTION We performed a systematic search for randomized controlled trials (RCTs) that compared enteral probiotics or synbiotics to placebo or no treatment in critically ill patients. We screened studies independently and in duplicate. DATA EXTRACTION Independent reviewers extracted data in duplicate. A random-effects model was used to pool data. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS Sixty-five RCTs enrolled 8,483 patients. Probiotics may reduce ventilator-associated pneumonia (VAP) (relative risk [RR], 0.72; 95% CI, 0.59 to 0.89 and risk difference [RD], 6.9% reduction; 95% CI, 2.7-10.2% fewer; low certainty), healthcare-associated pneumonia (HAP) (RR, 0.70; 95% CI, 0.55-0.89; RD, 5.5% reduction; 95% CI, 8.2-2.0% fewer; low certainty), ICU length of stay (LOS) (mean difference [MD], 1.38 days fewer; 95% CI, 0.57-2.19 d fewer; low certainty), hospital LOS (MD, 2.21 d fewer; 95% CI, 1.18-3.24 d fewer; low certainty), and duration of invasive mechanical ventilation (MD, 2.53 d fewer; 95% CI, 1.31-3.74 d fewer; low certainty). Probiotics probably have no effect on mortality (RR, 0.95; 95% CI, 0.87-1.04 and RD, 1.1% reduction; 95% CI, 2.8% reduction to 0.8% increase; moderate certainty). Post hoc sensitivity analyses without high risk of bias studies negated the effect of probiotics on VAP, HAP, and hospital LOS. CONCLUSIONS Low certainty RCT evidence suggests that probiotics or synbiotics during critical illness may reduce VAP, HAP, ICU and hospital LOS but probably have no effect on mortality.
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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.
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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
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Manzanares W, Lemieux M, Langlois PL, Wischmeyer PE. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2016; 19:262. [PMID: 27538711 PMCID: PMC4991010 DOI: 10.1186/s13054-016-1434-y] [Citation(s) in RCA: 199] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 07/22/2016] [Indexed: 12/16/2022]
Abstract
Background Critical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections. Probiotics are living non-pathogenic microorganisms, which may protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent infection. The purpose of this updated systematic review is to evaluate the overall efficacy of probiotics and synbiotic mixtures on clinical outcomes in critical illness. Methods Computerized databases from 1980 to 2016 were searched. Randomized controlled trials (RCT) evaluating clinical outcomes associated with probiotic therapy as a single strategy or in combination with prebiotic fiber (synbiotics). Overall number of new infections was the primary outcome; secondary outcomes included mortality, ICU and hospital length of stay (LOS), and diarrhea. Subgroup analyses were performed to elucidate the role of other key factors such as probiotic type and patient mortality risk on the effect of probiotics on outcomes. Results Thirty trials that enrolled 2972 patients were identified for analysis. Probiotics were associated with a significant reduction in infections (risk ratio 0.80, 95 % confidence interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I2 = 36 %, P = 0.09). Further, a significant reduction in the incidence of ventilator-associated pneumonia (VAP) was found (risk ratio 0.74, 95 % CI 0.61, 0. 90, P = 0.002; I2 = 19 %). No effect on mortality, LOS or diarrhea was observed. Subgroup analysis indicated that the greatest improvement in the outcome of infections was in critically ill patients receiving probiotics alone versus synbiotic mixtures, although limited synbiotic trial data currently exists. Conclusion Probiotics show promise in reducing infections, including VAP in critical illness. Currently, clinical heterogeneity and potential publication bias reduce strong clinical recommendations and indicate further high quality clinical trials are needed to conclusively prove these benefits.
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Affiliation(s)
- William Manzanares
- Department of Critical Care, Intensive Care Unit, Hospital de Clínicas (University Hospital), Faculty of Medicine, Universidad de la República (UdelaR), Italia Av, 14th Floor, 11.600, Montevideo, Uruguay
| | - Margot Lemieux
- Clinical Evaluation Research Unit. Angada 4, Kingston General Hospital, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada
| | - Pascal L Langlois
- Département de Anesthésie et de Réanimation, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke-Hôpital Fleurimont, Pièce 3610 3001, 12e Avenue Nord, Sherbrooke, QC, J1H 5N4, Canada
| | - Paul E Wischmeyer
- Department of Anesthesiology and Pediatrics (Nutrition Section), University of Colorado, School of Medicine, 12700 E. 19th Ave., RC2 P15-7120, Box 8602, Aurora, CO, 80045, USA.
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Blumenstein I, Shastri YM, Stein J. Gastroenteric tube feeding: techniques, problems and solutions. World J Gastroenterol 2014; 20:8505-8524. [PMID: 25024606 PMCID: PMC4093701 DOI: 10.3748/wjg.v20.i26.8505] [Citation(s) in RCA: 264] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2013] [Revised: 02/23/2014] [Accepted: 04/15/2014] [Indexed: 02/06/2023] Open
Abstract
Gastroenteric tube feeding plays a major role in the management of patients with poor voluntary intake, chronic neurological or mechanical dysphagia or gut dysfunction, and patients who are critically ill. However, despite the benefits and widespread use of enteral tube feeding, some patients experience complications. This review aims to discuss and compare current knowledge regarding the clinical application of enteral tube feeding, together with associated complications and special aspects. We conducted an extensive literature search on PubMed, Embase and Medline using index terms relating to enteral access, enteral feeding/nutrition, tube feeding, percutaneous endoscopic gastrostomy/jejunostomy, endoscopic nasoenteric tube, nasogastric tube, and refeeding syndrome. The literature showed common routes of enteral access to include nasoenteral tube, gastrostomy and jejunostomy, while complications fall into four major categories: mechanical, e.g., tube blockage or removal; gastrointestinal, e.g., diarrhea; infectious e.g., aspiration pneumonia, tube site infection; and metabolic, e.g., refeeding syndrome, hyperglycemia. Although the type and frequency of complications arising from tube feeding vary considerably according to the chosen access route, gastrointestinal complications are without doubt the most common. Complications associated with enteral tube feeding can be reduced by careful observance of guidelines, including those related to food composition, administration rate, portion size, food temperature and patient supervision.
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Dhaliwal R, Cahill N, Lemieux M, Heyland DK. The Canadian critical care nutrition guidelines in 2013: an update on current recommendations and implementation strategies. Nutr Clin Pract 2014; 29:29-43. [PMID: 24297678 DOI: 10.1177/0884533613510948] [Citation(s) in RCA: 178] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Clinical practice guidelines (CPGs) are systematically developed statements to assist practitioners and patient decisions about appropriate healthcare for specific clinical circumstances, and are designed to minimize practice variation, improve costs, and improve clinical outcomes. The Canadian Critical Care Practice Guidelines (CCPGs) were first published in 2003 and most recently updated in 2013. A total of 68 new randomized controlled trials were identified since the last version in 2009, 50 of them published between 2009 and 2013. The remaining articles were trials published before 2009 but were not identified in previous iterations of the CCPGs. For clinical practice guidelines to be useful to practitioners, they need to be up-to-date and be reflective of the current body of evidence. Herein we describe the process by which the CCPGs were updated. This process resulted in 10 new sections or clinical topics. Of the old clinical topics, 3 recommendations were upgraded, 4 were downgraded, and 27 remained the same. To influence decision making at the bedside, these updated guidelines need to be accompanied by active guideline implementation strategies. Optimal implementation strategies should be guided by local contextual factors including barriers and facilitators to best practice recommendations. Moreover, evaluating and monitoring performance, such as participating in the International Nutrition Survey of practice, should be part of any intensive care unit's performance improvement strategy. The active implementation of the updated CCPGs may lead to better nutrition care and improved patient outcomes in the critical care setting.
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Affiliation(s)
- Rupinder Dhaliwal
- Daren K. Heyland, MSc, Department of Public Health Sciences, Queen's University, 76 Stuart St, Kingston, ON K7L 2V7, Canada.
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Kelesidis T, Pothoulakis C. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Therap Adv Gastroenterol 2012; 5:111-25. [PMID: 22423260 PMCID: PMC3296087 DOI: 10.1177/1756283x11428502] [Citation(s) in RCA: 218] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Several clinical trials and experimental studies strongly suggest a place for Saccharomyces boulardii as a biotherapeutic agent for the prevention and treatment of several gastrointestinal diseases. S. boulardii mediates responses resembling the protective effects of the normal healthy gut flora. The multiple mechanisms of action of S. boulardii and its properties may explain its efficacy and beneficial effects in acute and chronic gastrointestinal diseases that have been confirmed by clinical trials. Caution should be taken in patients with risk factors for adverse events. This review discusses the evidence for efficacy and safety of S. boulardii as a probiotic for the prevention and therapy of gastrointestinal disorders in humans.
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Affiliation(s)
- Theodoros Kelesidis
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Charalabos Pothoulakis
- Inflammatory Bowel Disease Center, Div. of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA
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Abstract
Enteral nutrition is a nutritional therapy that is used in up to 10% of hospitalized patients. It involves a dramatic change in the provision of nutrients to the intestine and this, along with metabolic stress and drugs used, is responsible for a marked dysbiosis. Even though there is a huge level of between-subject variability, this dysbiosis is characterized by a decrease in the dominant flora, an increase in potentially pathogenic microorganisms and a reduction in the number of individual strains. The main characteristic of these changes in the microbiota is diarrhea, which has many consequences in these patients. Saccharomyces boulardii is able to prevent enteral nutrition-associated diarrhea, probably through an increase in short-chain fatty acid production. Alongside its role in the onset and prevention of diarrhea, the microbiota may be involved in energy harvesting and changes in the nutritional status. Manipulations of the microbiota may therefore be a novel way to increase feeding efficiency in tube-fed patients.
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Affiliation(s)
- S-M Schneider
- Division of Digestive Diseases, University Hospital of Nice, France.
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Whelan K, Myers CE. Safety of probiotics in patients receiving nutritional support: a systematic review of case reports, randomized controlled trials, and nonrandomized trials. Am J Clin Nutr 2010; 91:687-703. [PMID: 20089732 DOI: 10.3945/ajcn.2009.28759] [Citation(s) in RCA: 117] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Probiotics are increasingly used in patients receiving nutritional support; however, some case reports and trials have questioned their safety in such patients. OBJECTIVE The objective was to investigate the safety of probiotics in patients receiving nutritional support through a systematic review of case reports, randomized controlled trials (RCTs), and nonrandomized trials. DESIGN The systematic review followed Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. Six electronic databases were searched, a hand search of conference proceedings and reference lists was performed, and experts were contacted. Case reports, RCTs, and nonrandomized trials of probiotic use in patients also receiving enteral or parenteral nutrition were included in the review. Two reviewers independently screened the relevant articles and extracted the data. RESULTS In total, 1966 articles were identified, of which 72 fulfilled the inclusion criteria. There were 20 case reports of adverse events in 32 patients, all of which were infections due to Lactobacillus rhamnosus GG or Saccharomyces boulardii; the risk factors included central venous catheters and disorders associated with increased bacterial translocation. There were 52 articles reporting 53 trials in which 4131 patients received probiotics. Most trials showed either no effect or a positive effect on outcomes related to safety (eg, mortality and infections). Only 3 trials showed increased complications, which were largely noninfectious in nature and in specific patient groups (eg, transplant and pancreatitis). In 2 of these trials, the probiotic was administered through a postpyloric tube. CONCLUSION Many probiotics have been used safely in patients receiving nutritional support, although some probiotic products (strains or combinations) have been shown to increase the risk of complications in specific patient groups.
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Bengmark S, M. Schneider S. Rôles des manipulations du microbiote intestinal en réanimation. NUTR CLIN METAB 2009. [DOI: 10.1016/j.nupar.2009.10.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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McFarland LV, Bernasconi P. Saccharomyces boulardii'. A Review of an Innovative Biotherapeutic Agent. MICROBIAL ECOLOGY IN HEALTH AND DISEASE 2009. [DOI: 10.3109/08910609309141323] [Citation(s) in RCA: 111] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- L. V. McFarland
- Department of Medicinal Chemistry, University of Washington, Seattle, Washington
- Department of Medicinal Chemistry, Biocodex, Inc., Seattle, Washington, USA
| | - P. Bernasconi
- Department of Medicinal Chemistry, Laboratoires Biocodex, Montrouge, France
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Abstract
BACKGROUND Probiotics are defined as live micro-organisms which confer a health benefit on the host. Although most probiotics are bacteria, one strain of yeast, Saccharomyces boulardii, has been found to be an effective probiotic in double-blind clinical studies. AIMS To compare the main properties that differentiates yeast from bacteria and to review the properties of S. boulardii explaining its potential benefits as a probiotic. METHODS The PubMed and Medline databases were searched using the keywords 'probiotics', 'yeast', 'antibiotic associated diarrhea', 'Saccharomyces boulardii','bacterial diarrhea' and 'inflammatory bowel disease' in various combinations. RESULTS Several clinical studies have been conducted with S. boulardii in the treatment and prevention of various forms of diarrhoea. Promising research perspectives have been opened in terms of maintenance treatment of inflammatory bowel diseases. The mechanism of S. boulardii's action has been partially elucidated. CONCLUSION Saccharomyces boulardii is a strain of yeast which has been extensively studied for its probiotic effects. The clinical activity of S. boulardii is especially relevant to antibiotic-associated diarrhoea and recurrent Clostridium difficile intestinal infections. Experimental studies clearly demonstrate that S. boulardii has specific probiotic properties, and recent data has opened the door for new therapeutic uses of this yeast as an 'immunobiotic'.
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Affiliation(s)
- D Czerucka
- INSERM U 526, Faculté de Médecine, Université Nice-Sophia Antipolis, Nice Cedex 2, France.
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Schneider SM, Girard-Pipau F, Filippi J, Hebuterne X, Moyse D, Hinojosa GC, Pompei A, Rampal P. Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition. World J Gastroenterol 2005; 11:6165-9. [PMID: 16273644 PMCID: PMC4436634 DOI: 10.3748/wjg.v11.i39.6165] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the effects of Sb on fecal flora and short-chain fatty acids (SCFA) in patients on long-term TEN.
METHODS: Ten patients (3 females, 7 males, 59±5.5 years), on TEN for a median of 13 mo (1-125), and 15 healthy volunteers (4 females, 11 males, 32±2.0 years) received Sb (0.5 g bid PO) for 6 d. Two stool samples were taken before, on the last 2 d and 9-10 d after treatment, for SCFA measurement and for culture and bacterial identification. Values (mean±SE) were compared using sign tests and ANOVA.
RESULTS: Fecal butyrate levels were lower in patients (10.1±2.9 mmol/kg) than in controls (19.2±2.9, P = 0.02). Treatment with Sb increased total fecal SCFA levels in patients (150.2±27.2vs 107.5?8.2 mmol/kg, P = 0.02) but not in controls (129.0±28.6 vs 113.0±15.2 mmol/kg, NS). At the end of treatment with Sb, patients had higher fecal butyrate (16.0±4.4 vs 10.1 [2.9] mmol/kg, P = 0.004). Total SCFAs remained high 9 d after treatment was discon-tinued. Before the treatment, the anaerobe to aerobe ratio was lower in patients compared to controls (2.4±2.3 vs 69.8±1.8, P = 0.003). There were no significant changes in the fecal flora of TEN patients.
CONCLUSION: Sb-induced increase of fecal SCFA concentrations (especially butyrate) may explain the preventive effects of this yeast on TEN-induced diarrhea.
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Affiliation(s)
- Stephane-M Schneider
- Department of Gastroenterology and Clinical Nutrition, Archet University Hospital, BP 3079, F-06202 Nice Cedex 3, France.
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Buts JP, Bernasconi P. Saccharomyces boulardii: basic science and clinical applications in gastroenterology. Gastroenterol Clin North Am 2005; 34:515-32, x. [PMID: 16084311 DOI: 10.1016/j.gtc.2005.05.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Affiliation(s)
- Jean-Paul Buts
- Department of Pediatrics, Cliniques Universitaires St-Luc, Catholic University of Louvain, 10 Avenue Hippocrate, B-1200 Brussels, Belgium.
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Periti P, Tonelli F. Biotherapeutics and biotherapy of surgical enteropathies. Dig Liver Dis 2002; 34 Suppl 2:S87-97. [PMID: 12408450 DOI: 10.1016/s1590-8658(02)80174-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Probiotic agents are living micro-organisms that, upon ingestion, exert health benefits beyond inherent general nutrition. In this context, we must differentiate between biotherapeutics as approved drugs and dietary supplements and food products containing prebiotic bacteria that are not considered drugs. At present, the only biotherapeutic agent which is prescribable in some European countries, indicated to relieve specific diseases, is the yeast Saccharomyces boulardii. In this review, we consider the various pre-clinical and clinical aspects of biotherapeutics as basic drugs and the biotherapeutic powers of their use in the treatment of some surgical enteropathies.
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Abstract
Probiotics are nonpathogenic microorganisms which, when ingested, exert a positive influence on the health or physiology of the host. Their mechanisms of action and effects are now studied using the same pharmacological approach as for drugs. This article summarizes and comments on evidence for the positive effects of probiotics in various clinical situations. Substantial evidence can be achieved when randomized controlled trials or meta-analyses show positive results. The clinical situations studied include prevention or treatment of antibiotic-associated disorders, gastroenteritis, and diarrhea, lactose intolerance, intestinal infections and colonization by pathogenic bacteria (including Helicobacter pylori and Clostridium difficile), traveler's diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colonic cancer, urogenital infections and tumors, allergy (especially atopic eczema), vaccination, and cholesterol lowering. Current probiotics have an excellent safety record--another topic discussed in this article.
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Affiliation(s)
- Philippe R Marteau
- Gastroenterology Department, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, 20 rue Leblanc, 75908 Paris, France.
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Periti P, Tonelli F. Preclinical and clinical pharmacology of biotherapeutic agents: Saccharomyces boulardii. J Chemother 2001; 13:473-93. [PMID: 11760212 DOI: 10.1179/joc.2001.13.5.473] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Probiotic agents are living microorganisms that, upon ingestion, exert health benefits beyond inherent general nutrition. In this context, we must differentiate between biotherapeutics as approved drugs and dietary supplements and food products containing probiotic bacteria that are not considered drugs. At present the only biotherapeutic agent which is prescribable in some European countries, indicated to relieve specific diseases, is the yeast Saccharomyces boulardii. In this review we consider the various preclinical and clinical aspects of biotherapeutics as basic drugs and the biotherapeutic powers of their use in the treatment of some surgical enteropathies.
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Marteau PR, de Vrese M, Cellier CJ, Schrezenmeir J. Protection from gastrointestinal diseases with the use of probiotics. Am J Clin Nutr 2001; 73:430S-436S. [PMID: 11157353 DOI: 10.1093/ajcn/73.2.430s] [Citation(s) in RCA: 278] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Probiotics are nonpathogenic microorganisms that, when ingested, exert a positive influence on the health or physiology of the host. They can influence intestinal physiology either directly or indirectly through modulation of the endogenous ecosystem or immune system. The results that have been shown with a sufficient level of proof to enable probiotics to be used as treatments for gastrointestinal disturbances are 1) the good tolerance of yogurt compared with milk in subjects with primary or secondary lactose maldigestion, 2) the use of Saccharomyces boulardii and Enterococcus faecium SF 68 to prevent or shorten the duration of antibiotic-associated diarrhea, 3) the use of S. boulardii to prevent further recurrence of Clostridium difficile-associated diarrhea, and 4) the use of fermented milks containing Lactobacillus rhamnosus GG to shorten the duration of diarrhea in infants with rotavirus enteritis (and probably also in gastroenteritis of other causes). Effects that are otherwise suggested for diverse probiotics include alleviation of diarrhea of miscellaneous causes; prophylaxis of gastrointestinal infections, which includes traveler's diarrhea; and immunomodulation. Trials of gastrointestinal diseases that involve the ecosystem are currently being performed, eg, Helicobacter pylori infections, inflammatory bowel disease, and colon cancer.
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Affiliation(s)
- P R Marteau
- Gastroenterology Department, Hôpital Europèen Georges Lompidou, Assistance Publique des Hôpitaux de Paris and Paris V University, Paris
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Rodrigues AC, Cara DC, Fretez SH, Cunha FQ, Vieira EC, Nicoli JR, Vieira LQ. Saccharomyces boulardii stimulates sIgA production and the phagocytic system of gnotobiotic mice. J Appl Microbiol 2000; 89:404-14. [PMID: 11021572 DOI: 10.1046/j.1365-2672.2000.01128.x] [Citation(s) in RCA: 114] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The effect of Saccharomyces boulardii on the immune system was evaluated, comparing germ-free Swiss/NIH mice monoassociated with the probiotic with germ-free mice. Saccharomyces boulardii colonized the gut of germ-free mice and survived the gastrointestinal conditions. An increase in sIgA production, both total and anti-S. boulardii, was observed in the intestinal contents of monoassociated mice when compared with germ-free controls. The number of Kupffer cells was significantly higher in monoassociated mice than in germ-free controls. In S. boulardii-monoassociated mice, clearance of Escherichia coli B41 was higher than in germ-free controls. TNF-alpha, IFN-gamma and IL-12 serum levels were higher at earlier time points in monoassociated mice when compared with germ-free mice. These results show that the yeast S. boulardii modulates the host immune responses. This effect may be of interest for improving the resistance to enteropathogenic bacterial infections.
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Affiliation(s)
- A C Rodrigues
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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Gedek BR. Adherence of Escherichia coli serogroup O 157 and the Salmonella typhimurium mutant DT 104 to the surface of Saccharomyces boulardii. Mycoses 1999; 42:261-4. [PMID: 10424093 DOI: 10.1046/j.1439-0507.1999.00449.x] [Citation(s) in RCA: 89] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The detection of lectin sites for mannose-sensitive adhesion in the outer membrane of Saccharomyces boulardii and the irreversible binding of both enteropathogenic Escherichia coli (EPEC) and salmonellae (serovar Salmonella Typhimurium and Salmonella Enteritidis) provided the motivation to carry out further investigations to find out whether also other enteric bacteria such as entero-haemorrhagic Escherichia coli (EHEC) and the DT 104 mutant of S. Typhimurium have the capacity for binding to the cell wall of this yeast. Reference strains and fresh isolates from clinical cases of EHEC infections as well as salmonellae of the DT 104 mutant were included in this study using the agglutination test. The results first of all showed that EHEC of the serogroup O 157 and the DT 104 mutant of S. Typhimurium were bound to the surface of Saccharomyces boulardii. Because these bacteria do not respond very well to drugs but most of the gastrointestinal infections are caused by them, the use of S. boulardii for treatment and prophylaxis could be an excellent alternative.
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Affiliation(s)
- B R Gedek
- Sachverständige für Mikroökologie und Mykotoxinologie, Ismaning, Germany
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Vandenplas Y. Bacteria and yeasts in the treatment of acute and chronic infectious diarrhea. Part II: Yeasts. Clin Microbiol Infect 1999; 5:389-395. [PMID: 11853563 DOI: 10.1111/j.1469-0691.1999.tb00162.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Yvan Vandenplas
- Academic Children's Hospital, Free University of Brussels, Brussels, Belgium
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Brandão RL, Castro IM, Bambirra EA, Amaral SC, Fietto LG, Tropia MJ, Neves MJ, Dos Santos RG, Gomes NC, Nicoli JR. Intracellular signal triggered by cholera toxin in Saccharomyces boulardii and Saccharomyces cerevisiae. Appl Environ Microbiol 1998; 64:564-8. [PMID: 9464394 PMCID: PMC106083 DOI: 10.1128/aem.64.2.564-568.1998] [Citation(s) in RCA: 78] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
As is the case for Saccharomyces boulardii, Saccharomyces cerevisiae W303 protects Fisher rats against cholera toxin (CT). The addition of glucose or dinitrophenol to cells of S. boulardii grown on a nonfermentable carbon source activated trehalase in a manner similar to that observed for S.cerevisiae. The addition of CT to the same cells also resulted in trehalase activation. Experiments performed separately on the A and B subunits of CT showed that both are necessary for activation. Similarly, the addition of CT but not of its separate subunits led to a cyclic AMP (cAMP) signal in both S. boulardii and S. cerevisiae. These data suggest that trehalase stimulation by CT probably occurred through the cAMP-mediated protein phosphorylation cascade. The requirement of CT subunit B for both the cAMP signal and trehalase activation indicates the presence of a specific receptor on the yeasts able to bind to the toxin, a situation similar to that observed for mammalian cells. This hypothesis was reinforced by experiments with 125I-labeled CT showing specific binding of the toxin to yeast cells. The adhesion of CT to a receptor on the yeast surface through the B subunit and internalization of the A subunit (necessary for the cAMP signal and trehalase activation) could be one more mechanism explaining protection against the toxin observed for rats treated with yeasts.
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Affiliation(s)
- R L Brandão
- Laboratório de Fisologia e Bioquímica de Microorganismos, Escola de Farmácia, Universidade Federal de Ouro Preto, Brazil
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Tueux O. Techniques et modalités d'apport et de surveillance de la nutrition entérale. NUTR CLIN METAB 1998. [DOI: 10.1016/s0985-0562(98)80023-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Rodrigues AC, Nardi RM, Bambirra EA, Vieira EC, Nicoli JR. Effect of Saccharomyces boulardii against experimental oral infection with Salmonella typhimurium and Shigella flexneri in conventional and gnotobiotic mice. THE JOURNAL OF APPLIED BACTERIOLOGY 1996; 81:251-6. [PMID: 8810053 DOI: 10.1111/j.1365-2672.1996.tb04325.x] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Saccharomyces boulardii was shown to be capable of inhibiting multiplication of enteropathogenic bacteria in vitro and is currently used for its anti-diarrhoea properties. We studied the capacity of this yeast to antagonize Salmonella typhimurium and Shigella flexneri in the intestinal tract of conventional or gnotobiotic NMRI mice. Conventional animals were given daily 10 mg doses of S. boulardii, whereas germ-free animals were given a single 10 mg dose. Both groups were challenged orally 5 d later with the pathogenic bacteria (10(8) or 10(2) viable cells, respectively). Control groups were treated with saline instead of S. boulardii. Mortality and/or histopathological data showed a protective effect against the pathogenic bacteria in yeast-treated mice. Saccharomyces boulardii colonized the digestive tract of gnotobiotic mice and the number of viable cells ranged around 10(10) g-1 of faeces. In experimental and control gnotobiotic animals, Salm. typhimurium and Sh. flexneri became rapidly established at a level of about 10(10) viable cells g-1 of faeces and remained at high levels until the animals died or were sacrificed. The protection against Salm. typhimurium and Sh. flexneri obtained in conventional and/or gnotobiotic mice previously associated with S. boulardii is not due to the reduction of the bacterial populations in the intestines.
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Affiliation(s)
- A C Rodrigues
- Departmento de Microbiologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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Affiliation(s)
- C Roffe
- Department of Geriatric Medicine, Hope Hospital, Salford, U.K
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Viggiano M, Badetti C, Bernini V, Garabedian M, Manelli JC. [Saccharomyces boulardii fungemia in a patient with severe burns]. ANNALES FRANCAISES D'ANESTHESIE ET DE REANIMATION 1995; 14:356-8. [PMID: 8572392 DOI: 10.1016/s0750-7658(05)80603-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
A case of Saccharomyces boulardii fungaemia in a burn patient is reported. S. boulardii was administered in order to improve the digestive tolerance to enteral nutrition. After a surgical procedure, a sepsis syndrome occurred, with a white blood cell count increase, abdominal meteorism and respiratory insufficiency, associated with seven blood cultures positive to S. boulardii. Digestive translocation of the yeast seems to be the most likely origin of this fungaemia. Some fungaemias from S. boulardii have been published. However it is not usual to find such severe clinical features as in our case which leads us to reconsider the therapeutic use of S. boulardii in situations including a gastrointestinal tract suffering.
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Affiliation(s)
- M Viggiano
- Département d'Anesthesie-Réanimation, Centre Régional des Grands Brûlés, Hôpital de la Conception, Marseille
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Pothoulakis C, Castagliuolo I, Kelly CP, LaMont J. Clostridium difficile-associated diarrhea and colitis: pathogenesis and therapy. Int J Antimicrob Agents 1993; 3:17-32. [DOI: 10.1016/0924-8579(93)90003-n] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/1993] [Indexed: 11/30/2022]
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