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Moura-Oliveira V, Oliveira FMS, Moreno OLM, Ferreira JR, Szawka RE, Campideli-Santana AC, Teles J, Capettini LSA, Martins FS, Gomes MA. Amebicidal Activity of Escherichia coli Nissle 1917 Against Entamoeba histolytica. Microorganisms 2025; 13:828. [PMID: 40284664 PMCID: PMC12029587 DOI: 10.3390/microorganisms13040828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 03/07/2025] [Accepted: 03/18/2025] [Indexed: 04/29/2025] Open
Abstract
Amebiasis is a globally prevalent infection that can lead to fatal outcomes if not adequately treated. Conventional treatment with imidazoles often fails due to side effects and resistance, emphasizing the need for alternative therapies. The probiotic Escherichia coli Nissle 1917 (EcN) has shown potential in combating intestinal pathogens. This study aimed to evaluate the amebicidal activity of EcN in vitro and its effect on the production of reactive oxygen species (ROS). Trophozoites of Entamoeba histolytica (2.5 × 10⁴ cells/mL) were cultured in 96-well plates and exposed to varying concentrations of EcN (102-109 cells/mL). Plates were incubated at 36 °C for 6, 12, and 18 h, after which trophozoite viability was assessed. Intracellular ROS production, including superoxide and hydrogen peroxide, was measured using fluorescent probes. The highest efficacy was observed after 18 h at a CFU concentration of 109 cells/mL. Increased ROS production at all probiotic concentrations suggested a role in EcN's amebicidal mechanism. Morphological changes in trophozoites, such as rounding, vacuolization, and size reduction, were noted after EcN exposure, indicating growth inhibition. These findings suggest EcN induces structural and morphological changes in E. histolytica, inhibiting its growth in vitro. The findings suggest the potential efficacy of EcN; however, definitive confirmation requires data from human clinical trials.
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Affiliation(s)
- Vivian Moura-Oliveira
- Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; (V.M.-O.); (J.R.F.); (J.T.)
| | - Fabrício M. S. Oliveira
- Translational Type 2 Immunity Laboratory, Microbiology, Immunology and Tropical Medicine Department, George Washington School of Medicine and Health Sciences, Washington, DC 20052, USA;
| | - Olga L. M. Moreno
- Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; (O.L.M.M.); (L.S.A.C.)
| | - Julia R. Ferreira
- Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; (V.M.-O.); (J.R.F.); (J.T.)
| | - Raphael E. Szawka
- Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; (R.E.S.); (A.C.C.-S.)
| | - Ana C. Campideli-Santana
- Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; (R.E.S.); (A.C.C.-S.)
| | - Jullia Teles
- Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; (V.M.-O.); (J.R.F.); (J.T.)
| | - Luciano S. A. Capettini
- Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; (O.L.M.M.); (L.S.A.C.)
| | - Flaviano S. Martins
- Department of Microbiology, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil;
| | - Maria A. Gomes
- Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; (V.M.-O.); (J.R.F.); (J.T.)
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Kamani M, Karimi Torshizi MA, Shariatmadari F. Supplementation with Aspergillus fungi strain cultures on wheat bran on low-protein diets on performance, egg quality and blood characteristics of laying hens. Br Poult Sci 2025:1-10. [PMID: 40183648 DOI: 10.1080/00071668.2025.2479500] [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: 07/14/2024] [Accepted: 02/23/2025] [Indexed: 04/05/2025]
Abstract
1. In the contemporary economic-industrial world, ensuring the quality of poultry products through the use of healthy birds and providing nutritious diets has gained particular importance. The objective of this experiment was to evaluate the optimisation of laying hens' diets by reducing dietary protein by 4.61% and replacing it with 1.5 g/kg fermented wheat bran using two strains of Aspergillus niger and two strains of Aspergillus oryzae.2. This study was conducted on 240 laying hens at 41 weeks of age over 16 weeks, organised into four treatments and two control groups. One of the control groups included a diet with normal protein (CH) and another group with 4.61% less protein (CL). Both control groups received 1.5 g/kg raw wheat bran with their diet. In contrast, the four experimental treatments (N0, N4, O3, O4) received a diet with 4.61% less protein and 1.5 g/kg fermented wheat bran by their respective fungal strains, including two strains of A. niger-50101 (N0) and 92 844 (N4) and two strains of A. oryzae-5163 (O3) and 5164 (O4).3. The highest free radical scavenging activity, iron ion regenerative power and anticoagulant activity were observed in the control group containing uncultivated bran (p<0.05). A significant reduction in phytate content and an increase in total phenolic compounds in the fermented bran extract N4 fungi were observed (p<0.05). Additionally, this group showed the lowest level of egg yolk oxidation, as indicated by the induced malondialdehyde reaction.4. The N0 treatment had the highest feed intake and antioxidant activity in blood serum compared to the other groups (p < 0.05). The O4 group had the highest egg mass and egg weight, as well as the lowest levels of triglycerides and oxidation in the egg yolk compared to the other groups (p < 0.05).5. This study showed that fermenting wheat bran with Aspergillus spp. could enhance its antioxidant properties, which in turn improves egg quality.
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Affiliation(s)
- M Kamani
- Department of Poultry Science, Faculty of Agriculture, Tarbiat Modares University, Tehran, Iran
| | - M A Karimi Torshizi
- Department of Poultry Science, Faculty of Agriculture, Tarbiat Modares University, Tehran, Iran
| | - F Shariatmadari
- Department of Poultry Science, Faculty of Agriculture, Tarbiat Modares University, Tehran, Iran
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Dos Santos VHB, de Azevedo Ximenes ECP, de Souza RAF, da Silva RPC, da Conceição Silva M, de Andrade LVM, de Souza Oliveira VM, de Melo-Júnior MR, Costa VMA, de Barros Lorena VM, de Araújo HDA, de Lima Aires A, de Azevedo Albuquerque MCP. Effects of the probiotic Bacillus cereus GM on experimental schistosomiasis mansoni. Parasitol Res 2023; 123:72. [PMID: 38148420 DOI: 10.1007/s00436-023-08090-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 12/09/2023] [Indexed: 12/28/2023]
Abstract
Probiotics contribute to the integrity of the intestinal mucosa and preventing dysbiosis caused by opportunistic pathogens, such as intestinal helminths. Bacillus cereus GM obtained from Biovicerin® was cultured to obtain spores for in vivo evaluation on experimental schistosomiasis. The assay was performed for 90 days, where all animals were infected with 50 cercariae of Schistosoma mansoni on the 15th day. Three experimental groups were formed, as follows: G1-saline solution from the 1st until the 90th day; G2-B. cereus GM (105 spores in 300 μL of sterile saline) from the 1st until the 90th day; and G3-B. cereus GM 35th day (onset of oviposition) until the 90th day. G2 showed a significant reduction of 43.4% of total worms, 48.8% of female worms and 42.5% of eggs in the liver tissue. In G3, the reduction was 25.2%, 29.1%, and 44% of the total number of worms, female worms, and eggs in the liver tissue, respectively. G2 and G3 showed a 25% (p < 0.001) and 22% (p < 0.001) reduction in AST levels, respectively, but ALT levels did not change. ALP levels were reduced by 23% (p < 0.001) in the G2 group, but not in the G3. The average volume of granulomas reduced (p < 0.0001) 65.2% and 46.3% in the liver tissue and 83.0% and 53.2% in the intestine, respectively, in groups G2 and G3. Th1 profile cytokine (IFN-γ, TNF-α, and IL-6) and IL-17 were significantly increased (p < 0.001) stimulated with B. cereus GM in groups G2 and G3. IL-4 showed significant values when the stimulus was mediated by ConA. By modulating the immune response, B. cereus GM reduced the burden of worms, improved some markers of liver function, and reduced the granulomatous inflammatory reaction in mice infected with S. mansoni, especially when administered before infection.
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Affiliation(s)
- Victor Hugo Barbosa Dos Santos
- Instituto Keizo Asami (iLIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, PE, Brazil
| | - Eulália Camelo Pessoa de Azevedo Ximenes
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, PE, Brazil
- Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE, Brazil
| | - Renan Andrade Fernandes de Souza
- Instituto Keizo Asami (iLIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, PE, Brazil
| | | | | | | | - Valdenia Maria de Souza Oliveira
- Instituto Keizo Asami (iLIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil
- Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, PE, Brazil
| | | | - Vlaudia Maria Assis Costa
- Instituto Keizo Asami (iLIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil
- Departamento de Patologia, Universidade Federal de Pernambuco, Recife, PE, Brazil
| | | | - Hallysson Douglas Andrade de Araújo
- Instituto Keizo Asami (iLIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil
- Laboratório de Biotecnologia e Fármacos e Laboratório de Tecnologia de Biomateriais - Centro Acadêmico de Vitória de Santo Antão, Universidade Federal de Pernambuco, Recife, PE, Brazil
| | - André de Lima Aires
- Instituto Keizo Asami (iLIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil
- Centro de Ciências Médicas, Área Acadêmica de Medicina Tropical, Universidade Federal de Pernambuco, Recife, PE, Brazil
| | - Mônica Camelo Pessoa de Azevedo Albuquerque
- Instituto Keizo Asami (iLIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil.
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
- Centro de Ciências Médicas, Área Acadêmica de Medicina Tropical, Universidade Federal de Pernambuco, Recife, PE, Brazil.
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In vitro and in vivo evaluation of Bacillus clausii against Schistosoma mansoni. Acta Trop 2022; 235:106669. [PMID: 36037981 DOI: 10.1016/j.actatropica.2022.106669] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/28/2022] [Accepted: 08/25/2022] [Indexed: 11/17/2022]
Abstract
Experimental studies and clinical trials have been showing that probiotics are promising in the prevention and control of parasite infections. B. clausii, obtained from Enterogermina®, was cultured to obtain cell-free culture supernatant (CFS) and spores to evaluate its schistosomicidal effect in vitro and in vivo against Schistosoma mansoni, respectively. For in vitro and in vivo analysis mice were infected with 120 and 50 cercariae, respectively. Couples of adult worms, recovered on day 45 of infection, were exposed to CFS. The in vivo assay was performed for 100 days, where all animals were infected on the 30th day. Four experimental groups were formed, as follows: G1 - Saline solution from the 1st until the 100th day; G2 - B. clausii from the 1st until the 100th day; G3 - B. clausii from the 68th day (onset of oviposition) until the 100th day and G4 - PZQ (50 mg/Kg) from the 75th until the 79th day. In vitro, CFS of B. clausii does not caused mortality nor changed the motility on S. mansoni adult worms. G2 and G3 showed reduction of the 68.58 and 44.25% in the number of eggs eliminated in the feces and 34.29 and 53.6% and 22.8 and 48.49% the number of eggs trapped in the liver and intestine, respectively. Furthermore, in both therapeutic regimens G2 and G3, B. clausii increased the percentage of dead eggs in the intestinal tissue. B. clausii CFS, in vitro, does not showed action against S. mansoni and that treatment with B. clausii spores modulates favorably the parasitological parameters in the experimental infection of S. mansoni.
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Sarid L, Zanditenas E, Ye J, Trebicz-Geffen M, Ankri S. Insights into the Mechanisms of Lactobacillus acidophilus Activity against Entamoeba histolytica by Using Thiol Redox Proteomics. Antioxidants (Basel) 2022; 11:814. [PMID: 35624678 PMCID: PMC9137826 DOI: 10.3390/antiox11050814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/06/2022] [Accepted: 04/20/2022] [Indexed: 01/27/2023] Open
Abstract
Amebiasis is an intestinal disease transmitted by the protist parasite, Entamoeba histolytica. Lactobacillus acidophilus is a common inhabitant of healthy human gut and a probiotic that has antimicrobial properties against a number of pathogenic bacteria, fungi, and parasites. The aim of this study was to investigate the amebicide activity of L. acidophilus and its mechanisms. For this purpose, E. histolytica and L. acidophilus were co-incubated and the parasite's viability was determined by eosin dye exclusion. The level of ozidized proteins (OXs) in the parasite was determined by resin-assisted capture RAC (OX-RAC). Incubation with L. acidophilus for two hours reduced the viability of E. histolytica trophozoites by 50%. As a result of the interaction with catalase, an enzyme that degrades hydrogen peroxide (H2O2) to water and oxygen, this amebicide activity is lost, indicating that it is mediated by H2O2 produced by L. acidophilus. Redox proteomics shows that L. acidophilus triggers the oxidation of many essential amebic enzymes such as pyruvate: ferredoxin oxidoreductase, the lectin Gal/GalNAc, and cysteine proteases (CPs). Further, trophozoites of E. histolytica incubated with L. acidophilus show reduced binding to mammalian cells. These results support L. acidophilus as a prophylactic candidate against amebiasis.
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Affiliation(s)
| | | | | | | | - Serge Ankri
- Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel; (L.S.); (E.Z.); (J.Y.); (M.T.-G.)
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Sarid L, Ankri S. Are Metabolites From the Gut Microbiota Capable of Regulating Epigenetic Mechanisms in the Human Parasite Entamoeba histolytica? Front Cell Dev Biol 2022; 10:841586. [PMID: 35300430 PMCID: PMC8921869 DOI: 10.3389/fcell.2022.841586] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 01/25/2022] [Indexed: 12/21/2022] Open
Abstract
The unicellular parasite Entamoeba histolytica inhabits the human gut. It has to adapt to a complex environment that consists of the host microbiota, nutritional stress, oxidative stress, and nitrosative stress. Adaptation to this complex environment is vital for the survival of this parasite. Studies have shown that the host microbiota shapes virulence and stress adaptation in E. histolytica. Increasing evidence suggests that metabolites from the microbiota mediate communication between the parasite and microbiota. In this review, we discuss the bacterial metabolites that regulate epigenetic processes in E. histolytica and the implications that this knowledge may have for the development of new anti-amebic strategies.
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Affiliation(s)
- Lotem Sarid
- Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Serge Ankri
- Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
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Ankri S. Entamoeba histolytica-Gut Microbiota Interaction: More Than Meets the Eye. Microorganisms 2021; 9:microorganisms9030581. [PMID: 33809056 PMCID: PMC7998739 DOI: 10.3390/microorganisms9030581] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/05/2021] [Accepted: 03/10/2021] [Indexed: 12/16/2022] Open
Abstract
Amebiasis is a disease caused by the unicellular parasite Entamoeba histolytica. In most cases, the infection is asymptomatic but when symptomatic, the infection can cause dysentery and invasive extraintestinal complications. In the gut, E. histolytica feeds on bacteria. Increasing evidences support the role of the gut microbiota in the development of the disease. In this review we will discuss the consequences of E. histolytica infection on the gut microbiota. We will also discuss new evidences about the role of gut microbiota in regulating the resistance of the parasite to oxidative stress and its virulence.
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Affiliation(s)
- Serge Ankri
- Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel
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Saccharomyces boulardii: What Makes It Tick as Successful Probiotic? J Fungi (Basel) 2020; 6:jof6020078. [PMID: 32512834 PMCID: PMC7344949 DOI: 10.3390/jof6020078] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 06/01/2020] [Accepted: 06/02/2020] [Indexed: 02/07/2023] Open
Abstract
Saccharomyces boulardii is a probiotic yeast often used for the treatment of GI tract disorders such as diarrhea symptoms. It is genetically close to the model yeast Saccharomyces cerevisiae and its classification as a distinct species or a S. cerevisiae variant has long been discussed. Here, we review the main genetic divergencies between S. boulardii and S. cerevisiae as a strategy to uncover the ability to adapt to the host physiological conditions by the probiotic. S. boulardii does possess discernible phenotypic traits and physiological properties that underlie its success as probiotic, such as optimal growth temperature, resistance to the gastric environment and viability at low pH. Its probiotic activity has been elucidated as a conjunction of multiple pathways, ranging from improvement of gut barrier function, pathogen competitive exclusion, production of antimicrobial peptides, immune modulation, and trophic effects. This review summarizes the participation of S. boulardii in these mechanisms and the multifactorial nature by which this yeast modulates the host microbiome and intestinal function.
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Czerucka D, Rampal P. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. World J Gastroenterol 2019; 25:2188-2203. [PMID: 31143070 PMCID: PMC6526157 DOI: 10.3748/wjg.v25.i18.2188] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 03/21/2019] [Accepted: 03/30/2019] [Indexed: 02/06/2023] Open
Abstract
The yeast Saccharomyces boulardii CNCM I-745 is one of the probiotics recommended for the prevention of antibiotic-associated diarrhea. Studies conducted in vivo and in vitro demonstrated that in the case of infectious diseases there are two potential sites of action of Saccharomyces boulardii CNCM I-745: (1) An action on enteropathogenic microorganisms (adhesion of bacteria and their elimination or an effect on their virulence factors: Toxins, lipopolysaccharide, etc.); and (2) a direct action on the intestinal mucosa (trophic effects, effects on epithelial reconstitution, anti-secretory effects, anti-inflammatory, immunomodulators). Oral administration of Saccharomyces boulardii CNCM I-745 to healthy subjects does not alter their microbiota. However, in the case of diseases associated with the use of antibiotics or chronic diarrhea, Saccharomyces boulardii CNCM I-745 can restore the intestinal microbiota faster. The interaction of Saccharomyces boulardii CNCM I-745 with the innate immune system have been recently demonstrated thus opening up a new therapeutic potential of this yeast in the case of diseases associated with intestinal infections but also other pathologies associated with dysbiosis such as inflammatory diseases.
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Affiliation(s)
- Dorota Czerucka
- Department of Human Health, Division of Ecosystems and Immunity, Center Scientific of Monaco, Monaco MC98000, Monaco
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Nagaraja S, Ankri S. Target identification and intervention strategies against amebiasis. Drug Resist Updat 2019; 44:1-14. [PMID: 31112766 DOI: 10.1016/j.drup.2019.04.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 04/27/2019] [Accepted: 04/30/2019] [Indexed: 12/22/2022]
Abstract
Entamoeba histolytica is the etiological agent of amebiasis, which is an endemic parasitic disease in developing countries and is the cause of approximately 70,000 deaths annually. E. histolytica trophozoites usually reside in the colon as a non-pathogenic commensal in most infected individuals (90% of infected individuals are asymptomatic). For unknown reasons, these trophozoites can become virulent and invasive, cause amebic dysentery, and migrate to the liver where they cause hepatocellular damage. Amebiasis is usually treated either by amebicides which are classified as (a) luminal and are active against the luminal forms of the parasite, (b) tissue and are effective against those parasites that have invaded tissues, and (c) mixed and are effective against the luminal forms of the parasite and those forms which invaded the host's tissues. Of the amebicides, the luminal amebicide, metronidazole (MTZ), is the most widely used drug to treat amebiasis. Although well tolerated, concerns about its adverse effects and the possible emergence of MTZ-resistant strains of E. histolytica have led to the development of new therapeutic strategies against amebiasis. These strategies include improving the potency of existing amebicides, discovering new uses for approved drugs (repurposing of existing drugs), drug rediscovery, vaccination, drug targeting of essential E. histolytica components, and the use of probiotics and bioactive natural products. This review examines each of these strategies in the light of the current knowledge on the gut microbiota of patients with amebiasis.
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Affiliation(s)
- Shruti Nagaraja
- Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Serge Ankri
- Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
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do Carmo MS, Santos CID, Araújo MC, Girón JA, Fernandes ES, Monteiro-Neto V. Probiotics, mechanisms of action, and clinical perspectives for diarrhea management in children. Food Funct 2019; 9:5074-5095. [PMID: 30183037 DOI: 10.1039/c8fo00376a] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Infectious diarrhea is the second most common cause of morbidity and mortality in children under 5 years of age in the underdeveloped areas of the world. Conventional treatment consists of rehydration, which may be coupled with antimicrobial agents in more severe bacterial infections or with antiprotozoal agents. In the last few decades, research on the use of probiotic strains, such as Lactobacillus rhamnosus GG ATCC 53013 (LGG), Lactobacillus reuteri DSM 17938 and Saccharomyces boulardii, has gained much attention to prevent and treat diarrheal diseases. However, they are rarely used in the clinical routine, perhaps because there are still gaps in the knowledge about the effective benefit to the patient in terms of the reduction of the duration of diarrhea and its prevention. Furthermore, only a few probiotic strains are safely indicated for usage in pediatric practice. This review summarizes the current knowledge on the antimicrobial mechanisms of probiotics on distinct enteropathogens and their role in stimulating host defense mechanisms against intestinal infections. In addition, we highlight the potential of probiotics for the treatment and prevention of diarrhea in children. We conclude that the use of probiotics is beneficial for both the treatment and prevention of diarrhea in children and that the identification of other candidate probiotics might represent an important advance to a greater reduction in hospital stays and to prevent infectious diarrhea in a larger portion of this population.
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Affiliation(s)
- Monique Santos do Carmo
- Programa de Pós-graduação em Ciências da Saúde, Universidade Federal do Maranhão, São Luís, MA, Brazil
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Kongkaew A, Tönjes J, Siemer M, Boontawan P, Rarey J, Boontawan A. Extractive Fermentation of Ethanol from Sweet Sorghum Using Vacuum Fractionation Technique: Optimization and Techno-Economic Assessment. INTERNATIONAL JOURNAL OF CHEMICAL REACTOR ENGINEERING 2018. [DOI: 10.1515/ijcre-2017-0160] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Direct extraction of high purity ethanol from fermentation broth was investigated using a vacuum fractionation technique. Batch and repeated-batch extractive fermentation of ethanol were carried out using concentrated sweet sorghum as a carbon source. The effect of product inhibition was reduced by continuous removing ethanol from the fermented broth. About 60 % relative viability was observed in fermented broth with a higher productivity value. Due to the high value of living cells presented in the medium, repeated-batch extractive fermentation was subsequently performed. The ethanol was continuously fractionated out from the system at the average rate of 10.2 g/h with the concentration of approximately 80 wt%. There were 8 cycles of fermentation using only 1 time inoculation. Nevertheless, the calculated ethanol productivity and relative viability for each fermentation cycle were decreased gradually due to the accumulation of toxic substances in fermented broth. The simulation of 200 liters continuous extractive fermentation system using ASPEN PLUS was studied including process optimization and economical consideration. 18.5 liters of ethanol solutions 82 wt% with insignificant amounts of by-product was produced from a 200 liters extractive fermentation system per day. Production cost including raw material and utilities cost was approximately 0.71 €/liter. The economic and systemic performance process were subsequently analyzed, and including that ethanol loss was recovered using a gas scrubber connected to the vapor exiting the venturi tank as well as in the stillage stream. The calculated utility costs after process modification were 0.5 €/liter of ethanol, approximately 30 % of production cost was reduced.
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Surendran Nair M, Amalaradjou MA, Venkitanarayanan K. Antivirulence Properties of Probiotics in Combating Microbial Pathogenesis. ADVANCES IN APPLIED MICROBIOLOGY 2017; 98:1-29. [PMID: 28189153 DOI: 10.1016/bs.aambs.2016.12.001] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Probiotics are nonpathogenic microorganisms that confer a health benefit on the host when administered in adequate amounts. Ample evidence is documented to support the potential application of probiotics for the prevention and treatment of infections. Health benefits of probiotics include prevention of diarrhea, including antibiotic-associated diarrhea and traveler's diarrhea, atopic eczema, dental carries, colorectal cancers, and treatment of inflammatory bowel disease. The cumulative body of scientific evidence that demonstrates the beneficial effects of probiotics on health and disease prevention has made probiotics increasingly important as a part of human nutrition and led to a surge in the demand for probiotics in clinical applications and as functional foods. The ability of probiotics to promote health is attributed to the various beneficial effects exerted by these microorganisms on the host. These include lactose metabolism and food digestion, production of antimicrobial peptides and control of enteric infections, anticarcinogenic properties, immunologic enhancement, enhancement of short-chain fatty acid production, antiatherogenic and cholesterol-lowering attributes, regulatory role in allergy, protection against vaginal or urinary tract infections, increased nutritional value, maintenance of epithelial integrity and barrier, stimulation of repair mechanism in cells, and maintenance and reestablishment of well-balanced indigenous intestinal and respiratory microbial communities. Most of these attributes primarily focus on the effect of probiotic supplementation on the host. Hence, in most cases, it can be concluded that the ability of a probiotic to protect the host from infection is an indirect result of promoting overall health and well-being. However, probiotics also exert a direct effect on invading microorganisms. The direct modes of action resulting in the elimination of pathogens include inhibition of pathogen replication by producing antimicrobial substances like bacteriocins, competition for limiting resources in the host, antitoxin effect, inhibition of virulence, antiadhesive and antiinvasive effects, and competitive exclusion by competition for binding sites or stimulation of epithelial barrier function. Although much has been documented about the ability of probiotics to promote host health, there is limited discussion on the above mentioned effects of probiotics on pathogens. Being in an era of antibiotic resistance, a better understanding of this complex probiotic-pathogen interaction is critical for development of effective strategies to control infections. Therefore, this chapter will focus on the ability of probiotics to directly modulate the infectious nature of pathogens and the underlying mechanisms that mediate these effects.
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Sarjapuram N, Mekala N, Singh M, Tatu U. The Potential of Lactobacillus casei and Entercoccus faecium Combination as a Preventive Probiotic Against Entamoeba. Probiotics Antimicrob Proteins 2016; 9:142-149. [DOI: 10.1007/s12602-016-9232-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Dinleyici EC, Kara A, Ozen M, Vandenplas Y. Saccharomyces boulardii CNCM I-745 in different clinical conditions. Expert Opin Biol Ther 2014; 14:1593-609. [PMID: 24995675 DOI: 10.1517/14712598.2014.937419] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Saccharomyces boulardii is a well-known probiotic worldwide, and there are numerous studies including experimental and clinical trials in children and adults by the use of S. boulardii. AREAS COVERED The objective of the present report is to provide an update on the evidence for the efficacy of S. boulardii CNCM I-745 in different clinical conditions. Saccharomyces boulardii is one of the best-studied probiotics in acute gastroenteritis (AGE) and is shown to be safe and to reduce the duration of diarrhea and hospitalization by about 1 day. Saccharomyces boulardii is one of the recommended probiotics for AGE in children by European Society of Paediatric Infectious Diseases and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Saccharomyces boulardii is also a recommended probiotic for the prevention of antibiotic-associated diarrhea (AAD), and a recent study showed promising results for the treatment of AAD in children. There is insufficient evidence to recommend the long-term use of S. boulardii in patients with irritable bowel syndrome. Although some clinical studies showed positive effects of S. boulardii on inflammation, there is no clinical evidence that S. boulardii is useful in inflammatory bowel disease. Saccharomyces boulardii could be used in patients needing Helicobacter pylori eradication because the S. boulardii improves compliance, decreases the side effects and moderately increases the eradication rate. There are new promising results (improving feeding tolerance, shorten the course of hyperbilirubinemia), but we do still not recommend the routine use of S. boulardii in newborns. EXPERT OPINION Saccharomyces boulardii CNCM I-745 is a good example for the statement that each probiotic needs to be taxonomically characterized and its efficacy and safety should be documented individually in different clinical settings.
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Affiliation(s)
- Ener Cagri Dinleyici
- Eskisehir Osmangazi University, Faculty of Medicine, Pediatric Intensive Care and Infectious Disease Unit , TR-26480 Eskisehir , Turkey +90 542 2423608 ;
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Feizizadeh S, Salehi-Abargouei A, Akbari V. Efficacy and safety of Saccharomyces boulardii for acute diarrhea. Pediatrics 2014; 134:e176-91. [PMID: 24958586 DOI: 10.1542/peds.2013-3950] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND OBJECTIVE The efficacy of Saccharomyces boulardii for treatment of childhood diarrhea remains unclear. Our objective was to systematically review data on the effect of S. boulardii on acute childhood diarrhea. METHODS Our data sources included Medline, Embase, CINAHL, Scopus, and The Cochrane Library up to September 2013 without language restrictions. Randomized controlled trials and non-randomized trials that evaluated effectiveness of S. boulardii for treatment of acute diarrhea in children were included. Two reviewers independently evaluated studies for eligibility and quality and extracted the data. RESULTS In total, 1248 articles were identified, of which 22 met the inclusion criteria. Pooling data from trials showed that S. boulardii significantly reduced the duration of diarrhea (mean difference [MD], -19.7 hours; 95% confidence interval [CI], -26.05 to -13.34), stool frequency on day 2 (MD, -0.74; 95% CI, -1.38 to -0.10) and day 3 (MD, -1.24; 95% CI, -2.13 to -0.35), the risk for diarrhea on day 3 (risk ratio [RR], 0.41; 95% CI, 0.27 to 0.60) and day 4 (RR, 0.38; 95% CI, 0.24 to 0.59) after intervention compared with control. The studies included in this review were varied in the definition of diarrhea, the termination of diarrhea, inclusion and exclusion criteria, and their methodological quality. CONCLUSIONS This review and meta-analysis show that S. boulardii is safe and has clear beneficial effects in children who have acute diarrhea. However, additional studies using head-to-head comparisons are needed to define the best dosage of S. boulardii for diarrhea with different causes.
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Affiliation(s)
- Sahar Feizizadeh
- Department of Pharmaceutical Biotechnology and Isfahan Pharmaceutical Research Center, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amin Salehi-Abargouei
- Nutrition and Food Security Research Center, andDepartment of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Vajihe Akbari
- Department of Pharmaceutical Biotechnology and Isfahan Pharmaceutical Research Center, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran;
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Khatri I, Akhtar A, Kaur K, Tomar R, Prasad GS, Ramya TNC, Subramanian S. Gleaning evolutionary insights from the genome sequence of a probiotic yeast Saccharomyces boulardii. Gut Pathog 2013; 5:30. [PMID: 24148866 PMCID: PMC3843575 DOI: 10.1186/1757-4749-5-30] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 10/14/2013] [Indexed: 01/09/2023] Open
Abstract
Background The yeast Saccharomyces boulardii is used worldwide as a probiotic to alleviate the effects of several gastrointestinal diseases and control antibiotics-associated diarrhea. While many studies report the probiotic effects of S. boulardii, no genome information for this yeast is currently available in the public domain. Results We report the 11.4 Mbp draft genome of this probiotic yeast. The draft genome was obtained by assembling Roche 454 FLX + shotgun data into 194 contigs with an N50 of 251 Kbp. We compare our draft genome with all other Saccharomyces cerevisiae genomes. Conclusions Our analysis confirms the close similarity of S. boulardii to S. cerevisiae strains and provides a framework to understand the probiotic effects of this yeast, which exhibits unique physiological and metabolic properties.
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Affiliation(s)
- Indu Khatri
- CSIR-Institute of Microbial Technology, Chandigarh, India
| | - Akil Akhtar
- CSIR-Institute of Microbial Technology, Chandigarh, India
| | - Kamaldeep Kaur
- CSIR-Institute of Microbial Technology, Chandigarh, India
| | - Rajul Tomar
- CSIR-Institute of Microbial Technology, Chandigarh, India
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Hatoum R, Labrie S, Fliss I. Antimicrobial and probiotic properties of yeasts: from fundamental to novel applications. Front Microbiol 2012; 3:421. [PMID: 23267352 PMCID: PMC3525881 DOI: 10.3389/fmicb.2012.00421] [Citation(s) in RCA: 163] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Accepted: 11/21/2012] [Indexed: 12/11/2022] Open
Abstract
The yeasts constitute a large and heterogeneous group of microorganisms that are currently attracting increased attention from scientists and industry. Numerous and diverse biological activities make them promising candidates for a wide range of applications not limited to the food sector. In addition to their major contribution to flavor development in fermented foods, their antagonistic activities toward undesirable bacteria, and fungi are now widely known. These activities are associated with their competitiveness for nutrients, acidification of their growth medium, their tolerance of high concentrations of ethanol, and release of antimicrobial compounds such as antifungal killer toxins or "mycocins" and antibacterial compounds. While the design of foods containing probiotics (microorganisms that confer health benefits) has focused primarily on Lactobacillus and Bifidobacterium, the yeast Saccharomyces cerevisiae var. boulardii has long been known effective for treating gastroenteritis. In this review, the antimicrobial activities of yeasts are examined. Mechanisms underlying this antagonistic activity as well as recent applications of these biologically active yeasts in both the medical and veterinary sectors are described.
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Affiliation(s)
- Rima Hatoum
- Nutraceuticals and Functional Foods Institute, STELA Dairy Research Centre, Université LavalQuébec, QC, Canada
| | - Steve Labrie
- Nutraceuticals and Functional Foods Institute, STELA Dairy Research Centre, Université LavalQuébec, QC, Canada
| | - Ismail Fliss
- Nutraceuticals and Functional Foods Institute, STELA Dairy Research Centre, Université LavalQuébec, QC, 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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Amoeba Provide Insight into the Origin of Virulence in Pathogenic Fungi. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2012; 710:1-10. [DOI: 10.1007/978-1-4419-5638-5_1] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Thomas S, Metzke D, Schmitz J, Dörffel Y, Baumgart DC. Anti-inflammatory effects of Saccharomyces boulardii mediated by myeloid dendritic cells from patients with Crohn's disease and ulcerative colitis. Am J Physiol Gastrointest Liver Physiol 2011; 301:G1083-92. [PMID: 21903765 DOI: 10.1152/ajpgi.00217.2011] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Saccharomyces boulardii (Sb) is a probiotic yeast that has demonstrated efficacy in pilot studies in patients with inflammatory bowel disease (IBD). Microbial antigen handling by dendritic cells (DC) is believed to be of critical importance for immunity and tolerance in IBD. The aim was to characterize the effects of Sb on DC from IBD patients. Highly purified (>95%), lipopolysaccharide-stimulated CD1c(+)CD11c(+)CD123(-) myeloid DC (mDC) from patients with ulcerative colitis (UC; n = 36), Crohn's disease (CD; n = 26), or infectious controls (IC; n = 4) were cultured in the presence or absence of fungal supernatant from Sb (SbS). Phenotype and cytokine production and/or secretion of IBD mDC were measured by flow cytometry and cytometric bead arrays, respectively. T cell phenotype and proliferation were assessed in a mixed lymphocyte reaction (MLR) with allogenic CD4(+)CD45RA(+) naïve T cells from healthy donors. Mucosal healing was investigated in epithelial wounding and migration assays with IEC-6 cells. SbS significantly decreased the frequency of CD40-, CD80-, and CD197 (CCR7; chemokine receptor-7)-expressing IBD mDC and reduced their secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6 while increasing IL-8. In the MLR, SbS significantly inhibited T cell proliferation induced by IBD mDC. Moreover, SbS inhibited T(H)1 (TNF-α and interferon-γ) polarization induced by UC mDC and promoted IL-8 and transforming growth factor-β-dependent mucosal healing. In summary, we provide novel evidence of synergistic mechanisms how Sb controls inflammation (inhibition of T cell costimulation and inflammation-associated migration and mobilization of DC) and promotes epithelial restitution relevant in IBD.
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Affiliation(s)
- Saskia Thomas
- Division of Gastroenterology and Hepatology, Department of Medicine, Charité Medical Center-Virchow Hospital, Medical School of the Humboldt-University of Berlin, Berlin, Germany
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Vouloumanou EK, Makris GC, Karageorgopoulos DE, Falagas ME. Probiotics for the prevention of respiratory tract infections: a systematic review. Int J Antimicrob Agents 2009; 34:197.e1-10. [PMID: 19179052 DOI: 10.1016/j.ijantimicag.2008.11.005] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2008] [Accepted: 11/04/2008] [Indexed: 12/16/2022]
Abstract
We evaluated the clinical evidence regarding probiotic use for the prevention of respiratory tract infections (RTIs). Randomised controlled trials (RCTs) studying the effects of probiotics for the prevention of upper or lower RTIs were systematically identified. Fourteen RCTs (twelve involving healthy subjects and two involving patients with RTIs) were included. Various Lactobacillus strains were used in seven RCTs, combinations of Lactobacillus and Bifidobacterium strains were used in five RCTs, and a Bifidobacterium strain and a non-pathogenic Enterococcus faecalis strain were used in one RCT, respectively. In ten RCTs no difference was found regarding the incidence of RTIs in the probiotic arm compared with the control arm, whereas the remaining four RCTs favoured the use of probiotics. Reduction in the severity of symptoms related to RTIs was noted in five of six RCTs that provided relevant data. In three of nine RCTs that provided relevant data, the clinical course of RTIs was shorter in the probiotic arm, whereas no difference was found in the remaining six RCTs. In conclusion, probiotics may have a beneficial effect on the severity and duration of symptoms of RTIs but do not appear to reduce the incidence of RTIs.
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Affiliation(s)
- Evridiki K Vouloumanou
- Alfa Institute of Biomedical Sciences, 9 Neapoleos Street, 151 23 Marousi, Athens, Greece
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Thomas S, Przesdzing I, Metzke D, Schmitz J, Radbruch A, Baumgart DC. Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation. Clin Exp Immunol 2009; 156:78-87. [PMID: 19161443 DOI: 10.1111/j.1365-2249.2009.03878.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Saccharomyces boulardii (Sb) is a probiotic yeast preparation that has demonstrated efficacy in inflammatory and infectious disorders of the gastrointestinal tract in controlled clinical trials. Although patients clearly benefit from treatment with Sb, little is known on how Sb unfolds its anti-inflammatory properties in humans. Dendritic cells (DC) balance tolerance and immunity and are involved critically in the control of T cell activation. Thus, they are believed to have a pivotal role in the initiation and perpetuation of chronic inflammatory disorders, not only in the gut. We therefore decided to investigate if Sb modulates DC function. Culture of primary (native, non-monocyte-derived) human myeloid CD1c+CD11c+CD123(-) DC (mDC) in the presence of Sb culture supernatant (active component molecular weight < 3 kDa, as evaluated by membrane partition chromatography) reduced significantly expression of the co-stimulatory molecules CD40 and CD80 (P < 0.01) and the DC mobilization marker CC-chemokine receptor CCR7 (CD197) (P < 0.001) induced by the prototypical microbial antigen lipopolysaccharide (LPS). Moreover, secretion of key proinflammatory cytokines such as tumour necrosis factor-alpha and interleukin (IL)-6 were notably reduced, while the secretion of anti-inflammatory IL-10 increased. Finally, Sb supernatant inhibited the proliferation of naive T cells in a mixed lymphocyte reaction with mDC. In summary, our data suggest that Sb may exhibit part of its anti-inflammatory potential through modulation of DC phenotype, function and migration by inhibition of their immune response to bacterial microbial surrogate antigens such as LPS.
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Affiliation(s)
- S Thomas
- Department of Medicine, Division of Gastroenterology and Hepatology, Charité Medical Center-Virchow Hospital, Medical School of the Humboldt-University of Berlin, Berlin, Germany
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Ruszczyński M, Radzikowski A, Szajewska H. Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Aliment Pharmacol Ther 2008; 28:154-61. [PMID: 18410562 DOI: 10.1111/j.1365-2036.2008.03714.x] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Convincing evidence that probiotic administration can lower the risk of antibiotic-associated diarrhoea is limited to certain micro-organisms. AIM To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) for the prevention of antibiotic-associated diarrhoea in children. METHODS Children (aged 3 months to 14 years) with common infections were enrolled in a double-blind, randomized, placebo-controlled trial in which they received standard antibiotic treatment plus 2 x 10(10) colony forming units of a probiotic (n = 120) or a placebo (n = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat. RESULTS Any diarrhoea (>or=3 loose or watery stools/day for >or=48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2-0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1-1.06). No adverse events were observed. CONCLUSION Administration of L. rhamnosus (strains E/N, Oxy and Pen) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study.
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Affiliation(s)
- M Ruszczyński
- 2nd Department of Pediatrics, The Medical University of Warsaw, Warsaw, Poland
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Coming full circle: From antibiotics to probiotics and prebiotics. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2007; 15:161-3. [PMID: 18159486 DOI: 10.1155/2004/354909] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2004] [Accepted: 05/25/2004] [Indexed: 11/18/2022]
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Medellin-Peña MJ, Wang H, Johnson R, Anand S, Griffiths MW. Probiotics affect virulence-related gene expression in Escherichia coli O157:H7. Appl Environ Microbiol 2007; 73:4259-67. [PMID: 17496132 PMCID: PMC1932779 DOI: 10.1128/aem.00159-07] [Citation(s) in RCA: 145] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
The attachment of enterohemorrhagic Escherichia coli O157:H7 (EHEC O157) to host intestinal epithelial cells is essential for the development of hemorrhagic colitis and hemolytic-uremic syndrome in humans. Genes involved in attachment are carried within a pathogenicity island named the locus of enterocyte effacement (LEE), known to be directly activated by quorum sensing (QS). In the present study, we investigated autoinducer-2 (AI-2) production and the expression of several virulence-related genes in EHEC O157 grown in the absence and presence of a Lactobacillus acidophilus-secreted molecule(s). Transcription of important EHEC O157 virulence-related genes was studied by constructing promoter-reporter fusions and reverse transcriptase PCR. Shiga toxin (Stx) production was assayed by an enzyme immunoassay. When EHEC O157 was grown in the presence of chromatographically selected fractions of L. acidophilus La-5 cell-free spent medium, we observed a significant reduction of both extracellular AI-2 concentration and the expression of important virulence-related genes, although no significant difference in Stx production was observed. We show here that L. acidophilus La-5 secretes a molecule(s) that either acts as a QS signal inhibitor or directly interacts with bacterial transcriptional regulators, controlling the transcription of EHEC O157 genes involved in colonization.
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Besirbellioglu BA, Ulcay A, Can M, Erdem H, Tanyuksel M, Avci IY, Araz E, Pahsa A. Saccharomyces boulardii and infection due to Giardia lamblia. ACTA ACUST UNITED AC 2006; 38:479-81. [PMID: 16798698 DOI: 10.1080/00365540600561769] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Therapy with metronidazole is the recommended option in giardiasis. However, some clinical trial reports suggest the appearance of drug resistance to explain therapeutic failure. Several investigations have been carried out on the effect of probiotic microorganisms for preventing or treating gastrointestinal diseases, but little is known about their efficacy against protozoal infections. The principal objective of our study was to evaluate the efficacy of Saccharomyces boulardii against Giardia lamblia infections. A double-blind, placebo-controlled study was carried out on adult patients with giardiasis. Group 1 (30 patients) included metronidazole 750 mg 3 times daily along with S. boulardii capsules (250 mg b.i.d. orally) for 10 d while group 2 (35 patients) was treated with metronidazole 750 mg 3 times daily and with empty capsules as placebo for 10 d. Patients were re-examined at 2 and 4 weeks after treatment, and stool examinations were performed. At week 2, G. lamblia cysts were detected in 6 cases (17.1%) of group 2 and none in group 1. At the end of the fourth week, presence of the cysts continued in the same 6 cases in group 2 (control group). These findings indicated that S. boulardii may be effective in treating giardiasis when combined with metronidazole therapy.
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Affiliation(s)
- Bulent A Besirbellioglu
- Gulhane Military Medical Academy, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
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Szajewska H, Setty M, Mrukowicz J, Guandalini S. Probiotics in gastrointestinal diseases in children: hard and not-so-hard evidence of efficacy. J Pediatr Gastroenterol Nutr 2006; 42:454-75. [PMID: 16707966 DOI: 10.1097/01.mpg.0000221913.88511.72] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The use of probiotics, once discussed primarily in the context of alternative medicine, is now entering mainstream medicine. However, only a few of the potential health benefits attributed to probiotics have been confirmed in well-designed, well-conducted, randomized, controlled trials. This is especially true in the pediatric population. We review here the available evidence on efficacy of probiotics in children in the prevention and treatment of gastrointestinal diseases. Although we restrict our analysis to the pediatric age, whenever potentially relevant information is available only from adult studies, they are examined as well. Probiotics have been most extensively studied in the treatment of diarrheal diseases, where their efficacy can be considered well established. Studies documenting effects in other childhood gastrointestinal illnesses are few, although some preliminary results are promising. Furthermore, only a limited number of probiotic strains have been tested, and, as the effects of different probiotic microorganisms are not equivalent, results cannot be generalized. Thus, at present, we have some positive certainties, lots of exciting promises and many unanswered questions.
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Affiliation(s)
- Hania Szajewska
- Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Poland.
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Abstract
Probiotics, defined as microbial cell preparations or components of microbial cells that have a beneficial effect on the health and well being of the host, have traditionally been used to treat and prevent a variety of infections. Beneficial effects of probiotics in acute infectious diarrhea in children seem to be: (i) moderate; (ii) strain-dependent; (iii) dose dependent; (iv) significant in watery diarrhea and viral gastroenteritis, but non-existent in invasive, bacterial diarrhea; and (v) more evident when treatment with probiotics is initiated early in the course of disease. Three large, randomized controlled trials (RCTs) provide evidence of a very modest effect (statistically significant, but of questionable clinical importance) of some probiotic strains (Lactobaccillus GG, Lactobaccillus reuteri, Bifodobacterium lactis) on the prevention of community-acquired diarrhea. We have found conflicting evidence from four RCTs on the efficacy of Lactobacillus GG and B. bifidum and Streptococcus thermophilus in the prevention of nosocomial diarrhea in children. Two RCTs in children provide evidence of a moderate beneficial effect of Lactobacillus GG in the prevention of antibacterial-associated diarrhea (AAD), but results in adults are conflicting. Data on the efficacy of other probiotic strains in AAD in children are very limited. In conclusion, to date, the most extensively studied and best documented clinical application of probiotics in children is for the treatment of acute watery diarrhea of rotaviral or presumably viral etiology. Studies documenting effects in other types of diarrheal diseases in children are limited, although some preliminary results are promising. The effects of different probiotic microorganisms are not equal. Only very few probiotic strains have been tested rigorously in RCTs. Many questions remain to be answered. Future clinical trials should evaluate carefully selected, precisely defined probiotic strains and address clinically important endpoints.
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Affiliation(s)
- Hania Szajewska
- Department of Paediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland.
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Salvini F, Granieri L, Gemmellaro L, Giovannini M. Probiotics, Prebiotics and Child Health: Where are We Going? J Int Med Res 2004; 32:97-108. [PMID: 15080012 DOI: 10.1177/147323000403200201] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Changes in gastrointestinal (GI) bacteria caused by diet, antibiotics or other factors could alter enteric and systemic immune functions; changing the gut microflora composition by diet supplementation with specific live microbiota (probiotics) may be beneficial. The ‘natural’ target of ingested probiotics is the intestine, its microflora and associated immune system. Most published data concern use of probiotics to prevent and treat GI infections. Evidence for possible beneficial effects on mucosal barrier dysfunctions, including food allergy, inflammatory bowel disease, and respiratory and urinary tract infections, is emerging. The role of prebiotics (non-digestible oligosaccharides that reduce the growth or virulence of pathogens and induce systemic effects) is being investigated. Preliminary studies indicate that prebiotics may be useful dietary adjuncts for managing GI infections. Prebiotic and probiotic use in infants is attempting to modify a complex microbial ecosystem. Better understanding of the long-term effects of these interventions on infant gut microflora is an important goal.
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Affiliation(s)
- F Salvini
- Department of Paediatrics, University of Milan, San Paolo Hospital, Milan, Italy.
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Tasteyre A, Barc MC, Karjalainen T, Bourlioux P, Collignon A. Inhibition of in vitro cell adherence of Clostridium difficile by Saccharomyces boulardii. Microb Pathog 2002; 32:219-25. [PMID: 12071678 DOI: 10.1006/mpat.2002.0495] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The influence on the adherence of Clostridium difficile to Vero cells of the yeast Saccharomyces boulardii, the yeast fractions (cytoplasm and cell wall) and the culture supernatant was investigated in vitro. C. difficile adherence was significantly inhibited when bacteria were pre-incubated with the whole yeast and the cell wall fraction; this adherence inhibition was dose-dependent. The cell wall fraction also acts upon the target cultured cells inasmuch as the level of adherence was significantly decreased when Vero cells were preincubated with it. The same experiments carried out in the presence of an inhibitor of serine proteases resulted in no inhibition of bacterial adherence. These results suggest that the yeast could inhibit adherence of C. difficile to cells thanks to its proteolytic activity but also through steric hindrance.
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Affiliation(s)
- Albert Tasteyre
- Université Paris-Sud, Faculté de Pharmacie, Département de Microbiologie, rue J. B. Clément, 92296 Châtenay-Malabry Cedex, France
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Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr 2001; 33 Suppl 2:S17-25. [PMID: 11698781 DOI: 10.1097/00005176-200110002-00004] [Citation(s) in RCA: 269] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND This review was designed to assess the evidence from randomized controlled trials on effects of probiotics in the treatment and prevention of acute infectious diarrhea in infants and children. METHODS A systematic review of published, randomized, double-blind, placebo-controlled trials on probiotics in the treatment or prevention of acute diarrhea defined as >3 loose or watery stools per 24 hours in infants and children. RESULTS The use of probiotics as compared with placebo was associated with a significantly reduced risk of diarrhea lasting >3 days. The pooled estimate risk was 0.43 (95% CI, 0.34-0.53) with a fixed-effect model, and remained significant in a random-effect model (0.40; 95% CI, 0.28-0.57). Only Lactobacillus GG showed a consistent effect. Probiotics significantly reduced the duration of diarrhea when compared with placebo, particularly in rotaviral gastroenteritis-the pooled, weighted, mean difference (WMD) assuming the random-effect model was -20.1 hours (95% CI, -26.1 to -14.2) and -24.8 (95% CI, -31.8 to -17.9) respectively. A meta-analysis of the prevention studies was not feasible because of significant clinical and statistical heterogeneity. CONCLUSIONS There is evidence of a clinically significant benefit of probiotics in the treatment of acute infectious diarrhea in infants and children, particularly in rotaviral gastroenteritis. Lactobacillus GG showed the most consistent effect, although other probiotic strains may also be effective. Further research is needed. Clinical and statistical heterogeneity of the prophylactic interventions preclude drawing firm conclusions about the efficacy of probiotics in preventing acute gastroenteritis.
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Affiliation(s)
- H Szajewska
- Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland.
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Abstract
Biotherapeutic agents offer unique advantages over traditional treatments for infectious diarrhea, and several have been shown to be effective (Table 4). These therapeutic microbial agents are most effective in types of infectious diseases that are associated with a disruption of the normal intestinal microecology (e.g., AAD, C. difficile disease). The impact of biotherapeutic agents on rotaviral diarrhea is of special clinical importance because this is the most common cause of pediatric diarrhea, and there is no defined treatment. Strong efforts need to be made to limit antibiotic exposure in children. Biotherapeutic agents offer a safe and effective nonantibiotic method of treating this important pathogen, especially after the withdrawal of a rotaviral vaccine from the market by the FDA. However, for many biotherapeutic agents, well-done, placebo-controlled trials still are lacking, and not all types of infectious diarrhea respond to these agents. Continued research in this innovative therapeutic area is warranted.
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Affiliation(s)
- G W Elmer
- Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington, USA.
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Alvarez-Olmos MI, Oberhelman RA. Probiotic agents and infectious diseases: a modern perspective on a traditional therapy. Clin Infect Dis 2001; 32:1567-76. [PMID: 11340528 DOI: 10.1086/320518] [Citation(s) in RCA: 193] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2000] [Revised: 10/16/2000] [Indexed: 01/19/2023] Open
Abstract
There is an increasing scientific and commercial interest in the use of beneficial microorganisms, or "probiotics," for the prevention and treatment of disease. The microorganisms most frequently used as probiotic agents are lactic-acid bacteria such as Lactobacillus rhamnosus GG (LGG), which has been extensively studied in recent literature. Multiple mechanisms of action have been postulated, including lactose digestion, production of antimicrobial agents, competition for space or nutrients, and immunomodulation. We have reviewed recent studies of probiotics for the treatment and control of infectious diseases. Studies of pediatric diarrhea show substantial evidence of clinical benefits from probiotic therapy in patients with viral gastroenteritis, and data on LGG treatment for Clostridium difficile diarrhea appear promising. However, data to support use of probiotics for prevention of traveler's diarrhea are more limited. New research suggests potential applications in vaccine development and prevention of sexually transmitted diseases. Further studies are needed to take full advantage of this traditional medical approach and to apply it to the infectious diseases of the new millennium.
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Affiliation(s)
- M I Alvarez-Olmos
- Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
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Szajewska H, Kotowska M, Mrukowicz JZ, Armańska M, Mikołajczyk W. Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants. J Pediatr 2001; 138:361-5. [PMID: 11241043 DOI: 10.1067/mpd.2001.111321] [Citation(s) in RCA: 217] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Nosocomial diarrhea is a major problem in pediatric hospitals worldwide. We evaluated the efficacy of orally administered Lactobacillus GG (LGG) in the prevention of this disease in young children. STUDY DESIGN Eighty-one children aged 1 to 36 months who were hospitalized for reasons other than diarrhea were enrolled in a double-blind trial and randomly assigned at admission to receive LGG (n = 45) at a dose of 6 x 10(9) colony-forming units or a comparable placebo (n = 36) twice daily orally for the duration of their hospital stay. RESULTS LGG reduced the risk of nosocomial diarrhea (> or =3 loose or watery stools/24 h) in comparison with placebo (6.7% vs 33.3%; relative risk: 0.2; [95% CI: 0.06-0.6]; number needed to treat: 4 [95% CI: 2-10]). The prevalence of rotavirus infection was similar in LGG and placebo groups (20% vs 27.8%, respectively; relative risk: 0.72; 95% CI: 0.33-1.56). However, the use of LGG compared with placebo significantly reduced the risk of rotavirus gastroenteritis (1/45 [2.2%] vs 6/36 [16.7%], respectively; relative risk: 0.13; 95% CI: 0.02-0.79; number needed to treat: 7; 95% CI: 3-40). CONCLUSIONS Prophylactic use of LGG significantly reduced the risk of nosocomial diarrhea in infants, particularly nosocomial rotavirus gastroenteritis.
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Affiliation(s)
- H Szajewska
- Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland
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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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Abstract
Probiotics appear to be useful in the prevention or treatment of several gastrointestinal disorders, including infectious diarrhea, antibiotic diarrhea, and traveler's diarrhea. Results of preliminary human and animal studies suggest that patients with inflammatory diseases, and even irritable bowel syndrome, may benefit from probiotic therapy. Probiotics represent an exciting therapeutic advance, although much investigation must be undertaken before their role in gastroenterology is clearly delineated. Questions related to probiotic origin, survivability, and adherence are all important considerations for further study. More important, each probiotic proposed must be studied individually and extensively to determine its efficacy and safety in each disorder for which its use may be considered.
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Affiliation(s)
- J A Vanderhoof
- Department of Pediatrics, University of Nebraska, Omaha, USA
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