Boulardii CNCM I-745 Research Articles

Retrospective analysis of EMR database to assess the effectiveness of Saccharomyces boulardii CNCM I-745 in children with acute diarrhoea during routine clinical practice.

This study aimed to assess the efficacy of Saccharomyces boulardii, a yeast probiotic, in the management of acute diarrhoeal disorders in the paediatric population in outpatient settings. It was a multicentre retrospective analysis of medical records of children who were treated for acute diarrhoea by routine treatment (oral rehydration solution and zinc) with or without S. boulardii. Overall, 160 children presenting with acute diarrhoea at seven different outpatient paediatric settings were included in the study. Children were divided into two categories based on their treatment with S. boulardii (SB group) or without S. boulardii (Non-SB group). Baseline demographic, anthropometric and clinical variables were compared between the two groups. The median duration of diarrhoea post-treatment was significantly shorter in the S. boulardii group (3 days) than in the non-SB group (4 days). A significant reduction in the frequency of stools was observed post-treatment in the S. boulardii group (1.7 versus 2.5 in the non-SB group). There was a significant weight gain in the S. boulardii group post-treatment (300 g) in comparison with the non-SB group (mean loss of 400 g). This study established the positive role of S. boulardii in the management of acute diarrhoeal diseases in children. Moreover, the S. boulardii probiotic was seen to be effective in diarrhoeal diseases in children with dehydration.

Modeling the Ethanol Tolerance of the Probiotic Yeast Saccharomyces cerevisiae var. boulardii CNCM I-745 for its Possible Use in a Functional Beer.

Saccharomyces yeasts are able to ferment simple sugars to generate levels of ethanol that are toxic to other yeasts and bacteria. The tolerance to ethanol of different yeasts depends also on the incubation temperature. In this study, the ethanol stress responses of S. cerevisiae and the probiotic yeast S. boulardii CNCM I-745 were evaluated at two temperatures. The growth kinetics parameters were obtained by fitting the Baranyi and Roberts model to the experimental data. The four-parameter logistic Hill equation was used to describe the ethanol tolerance of the yeasts at the temperatures of 28 and 37°C. Adequate determination coefficients were obtained (R2 > 0.91) in all cases. S. boulardii grown at 28°C was selected as the yeast with the best ethanol tolerance (6-8%) for use in the elaboration of functional craft beers.

Saccharomyces boulardii CNCM I-745 probiotic does not alter the pharmacokinetics of amoxicillin.

Background Probiotics are live microbial organisms that provide benefit to the host while co-habitating in the gastrointestinal tract. Probiotics are safe, available over the counter, and have clinical benefit by reducing the number of antibiotic-associated diarrhea days. Prescriptions from providers and direct consumer demand of probiotics appear to be on the rise. Several recent animal studies have demonstrated that probiotics may have significant effect on absorption of co-administered drugs. However, to date, most probiotic-drug interaction studies in animal models have been limited to bacterial probiotics and nonantibiotic drugs. Methods We performed a traditional pharmacokinetic mouse study examining the interactions between a common commercially available yeast probiotic, Saccharomyces boulardii CNCM I-745 (Florastor®) and an orally administered amoxicillin. Results We showed that there were no significant differences in pharmacokinetic parameters (half-life, area under the curve, peak concentrations, time to reach maximum concentration, elimination rate constant) of amoxicillin between the probiotic treated and untreated control groups. Conclusions Altogether, our findings suggest that coadministration or concurrent use of S. boulardii probiotic and amoxicillin would not likely alter the efficacy of amoxicillin therapy.

Effect of Saccharomyces boulardii CNCM I-745 as complementary treatment of Helicobacter pylori infection on gut microbiome

Conventional therapy for H. pylori infection includes the combination of antibiotics and a proton-pump inhibitor. Addition of probiotics as adjuvants for H. pylori antibiotic treatment can increase eradication rate and decrease treatment side effects. Although many studies show the benefits of S. boulardii CNCM I-745 in the treatment of H. pylori infection, the mechanism by which those benefits are achieved is unknown. Here, we report clinical characteristics and fecal microbiota changes comparing conventional anti-H. pylori therapy versus conventional therapy supplemented with S. boulardii CNCM I-745. A total of 74 patients were included in the current study; patients positive for H. pylori (n = 63) were randomly assigned to 2 groups: 34 patients received conventional therapy and 29 antibiotic therapy plus 750mg of S. boulardii CNCM I-745 daily, for 2weeks. Eleven patients negative for H. pylori infection were also studied. Patients provided 3 fecal samples: before initiating the antibiotic treatment, upon its completion, and 1month after treatment. Patients were contacted every 72h to inquire about side effects and compliance. DNA was extracted, and 16S rRNA was amplified and sequenced on Illumina MiSeq. Bioinformatic analysis was performed using QIIME2. Patients who received the probiotic had a significantly lower frequency of associated gastrointestinal symptoms (P = 0.028); higher number of bacterial diversity evenness (P = 0.0156); higher abundance of Enterobacteria; and lower abundance of Bacteroides and Clostridia upon treatment completion. Addition of S. boulardii CNCM I-745 induced a lower frequency of gastrointestinal symptoms that could be related to changes in gut microbiota.

A53 SACCHAROMYCES BOULARDII CNCM I-745 IMPROVES ANXIETY-LIKE BEHAVIOR AND RESCUES DYSMOTILITY IN A HUMANIZED MOUSE MODEL OF IRRITABLE BOWEL SYNDROME WITH CO-MORBID ANXIETY

Abstract Background Irritable bowel syndrome (IBS) is one of the most common conditions seen by gastroenterologists for which there is no effective cure. The pathophysiology of IBS is multifactorial and poorly understood, but the condition is characterized by chronic abdominal pain accompanied by altered bowel habits in the absence of an underlying structural abnormality. IBS is frequently associated with psychiatric co-morbidities such as anxiety and depression and has been considered a disorder of gut-brain communication. We previously developed a humanized mouse model of IBS with co-morbid anxiety (IBS+A) by colonizing germ-free mice with fecal microbiota of IBS+A patients. Aims To test the therapeutic potential of the probiotic yeast Saccharomyces boulardii CNCM I-745 (S. bou) in preventing the transfer of the IBS+A phenotype and investigated underlying mechanisms. Methods Germ-free Swiss-Webster mice were colonized with fecal microbiota from an IBS+A patient or from a healthy subject (controls) and after three weeks they were gavaged daily for two weeks with 3g/kg/day of the probiotic S. bou (Biocodex–France) or water. Behavior, intestinal motility and permeability were assessed at sacrifice. Potential mechanisms were assessed by microbiota 16S rRNA gene sequencing, gene expression by Nanostring Counter Gene Expression and indole quantification by absorption using Kovak’s reagent. Results IBS+A colonized mice developed 25% faster gastrointestinal transit (P<0.05) and had a 3-fold longer latency time in the step-down test (P<0.001), indicative of anxiety-like behaviour compared with controls. S. bou normalized gastrointestinal transit (P<0.05) and shortened by 50% the step-down latency (P<0.01), compared to water-treated mice. Microbiota of IBS+A colonized mice had higher abundance of Unc. Erysipelotrichaceae and Unc. Coriobacteriaceae, and lower abundance of Oscillospira, Weissela, and Fructubacillus. S. bou treatment prevented these changes and the microbiota was similar to controls. Predicted function analysis in S. bou treated mice suggested higher number of genes implicated in indole biosynthesis (P<0.05) and S. bou increased indole levels by 20% in vitro. Finally, Trpv1, a gene implicated in visceral hypersensitivity and anxiety, was increased by 2-fold in IBS+A colonized mice compared with controls (P<0.001), and this was reverted by 20% (P<0.05) by S. bou treatment. Conclusions Our data indicate that Saccharomyces boulardii CNCM I-745 supplementation improves the intestinal and behavioral phonotype that is induced by IBS+A microbiota in mice. Putative mechanisms include regulation of indole production by bacteria and regulation of host Trpv1 gene expression. The results prompt investigation of S. bou in IBS patients with co-morbid anxiety. Funding Agencies Biocodex – Gentilly – France

Modulation of 5-fluorouracil activation of toll-like/MyD88/NF-κB/MAPK pathway by Saccharomyces boulardii CNCM I-745 probiotic

Background and aimChemotherapy drugs that act via Toll-like receptors (TLRs) can exacerbate mucosal injury through the production of cytokines. Intestinal mucositis can activate TLR2 and TLR4, resulting in the activation of NF-κB. Intestinal mucositis characterized by intense inflammation is the main side effect associated with 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii CNCM I-745 (S.b) is a probiotic yeast used in the treatment of gastrointestinal disorders. The main objective of the study was to evaluate the effect of S.b treatment on the Toll-like/MyD88/NF-κB/MAPK pathway activated during intestinal mucositis and in Caco-2 cells treated with 5-FU. MethodsThe mice were divided into three groups: saline (control), saline + 5-FU, and 5-FU + S.b (1.6 × 1010 colony forming units/kg). After 3 days of S.b administration by gavage, the mice were euthanized and the jejunum and ileum were removed. In vitro, Caco2 cells were treated with 5-FU (1 mM) alone or in the presence of lipopolysaccharide (1 ng/ml). When indicated, cells were exposed to S.b. The jejunum/ileum samples and Caco2 cells were examined for the expression or concentration of the inflammatory components. ResultsTreatment with S.b modulated the expressions of TLR2, TLR4, MyD88, NF-κB, ERK1/2, phospho-p38, phospho-JNK, TNF-α, IL-1β, and CXCL-1 in the jejunum/ileum and Caco2 cells following treatment with 5-FU. ConclusionToll-like/MyD88/NF-κB/MAPK pathway are activated during intestinal mucositis and their modulation by S.b suggests a novel and valuable therapeutic strategy for intestinal inflammation.

Saccharomyces boulardii CNCM I-745 changes lipidemic profile and gut microbiota in a hamster hypercholesterolemic model.

Hypercholesterolemia is a main risk factor of cardiovascular disease. Probiotics are a safe approach to reduce elevated cholesterol without any deleterious effect to human health. Saccharomyces boulardii CNCM I-745 probiotic properties are well documented in a context of intestinal dysbiosis. Recent in vitro and preclinical studies have suggested its potential effects on dyslipidemia. This is the first controlled study investigating the effects of S. boulardii CNCM I-745 on lipidemic profile and gut microbiota in a hamster hypercholesterolemic model. Daily administration (3 g/kg) of S. boulardii for 21 or 39 days in hamsters fed a 0.3% cholesterol-diet significantly reduced total plasma cholesterol (P<0.001) and increased faecal total cholesterol (P<0.05) compared to vehicle-treated animals. S. boulardii significantly modified the gut microbiota composition of the hamster fed a 0.3% cholesterol-diet. These microbial abundancy modifications of the microbiota were correlated to variations of lipidemic values or liver genes expressions. In particularly we found that abundance of g_Allobaculum, the most modified taxon after S. boulardii treatment (+236%; P<0.05), was correlated to variations in plasmatic lipoproteins level and ABCG5 hepatic gene expression. We also observed a not previously described correlation between the levels of g_Oxalobacter in the gut microbiota and total cholesterol plasma concentration. In conclusion, we confirmed the cholesterol-lowering effects of S. boulardii intake and we demonstrated for the first time the S. boulardii effect on gut microbiota in the context of hypercholesterolemia in hamsters. Our results provide new insights for a beneficial and safe approach of hypercholesterolemia treatment and could be considered for clinical development, alone or in addition to conventional treatment.

Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections.

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.

Saccharomyces boulardii Strain CNCM I-745 Modifies the Mononuclear Phagocytes Response in the Small Intestine of Mice Following Salmonella Typhimurium Infection.

Intestinal mononuclear phagocytes (MPs) comprise dendritic cells (DCs) and macrophages (Mφs) that play different roles in response to Salmonella infection. After phagocytosis, DCs expressing CD103 transport Salmonella from the intestinal tract to the mesenteric lymph nodes (MLN) and induce adaptive immune responses whereas resident Mφs expressing CX3CR1 capture bacteria in the lumen and reside in the lamina propria (LP) where they induce a local immune response. CX3CR1+ Mφs are generated from Ly6Chi monocytes that enter the colonic mucosa and differentiate locally. We previously demonstrated that the probiotic yeast Saccharomyces boulardii CNCM I-745 (S.b) prevents infection by Salmonella enterica serovar Typhimurium (ST), decreases ST translocation to the peripheral organs and modifies the pro-and anti-inflammatory cytokine profiles in the gut. In the present study, we investigated the effect of S.b on the migratory CD103+ DCs and the resident CX3CR1+ Mφs. MPs were isolated from the LP of streptomycin-treated mice infected by ST with or without S.b treatment before or during the infection. In S.b-pretreated mice, we observed a decrease of the CD103+ DCs in the LP that was associated with the drop of ST recovery from MLN. Interestingly, S.b induced an infiltration of LP by classical Ly6Chi monocytes, and S.b modified the monocyte-Mφ maturation process in ST-infected mice. Our results showed that S.b treatment induced the expansion of Ly6Chi monocytes in the blood as well as in the bone marrow (BM) of mice, thus contributing to the Mφ replenishment in LP from blood monocytes. In vitro experiments conducted on BM cells confirmed that S.b induced the expansion of CX3CR1+ Mφs and concomitantly ST phagocytosis. Altogether, these data demonstrate that Saccharomyces boulardii CNCM I-745 modulates the innate immune response. Although here, we cannot explicitly delineate direct effects on ST from innate immunity, S. b-amplified innate immunity correlated with partial protection from ST infection. This study shows that S.b can induce the expansion of classical monocytes that are precursors of resident Mφs in the LP.

Saccharomyces boulardii CNCM I-745 Modulates the Fecal Bile Acids Metabolism During Antimicrobial Therapy in Healthy Volunteers.

Saccharomyces boulardii CNCM I-745 (SB) is a probiotic yeast used to lower the incidence of antibiotic-associated Clostridium difficile (C. difficile) infection, though its mechanism of action remains unclear. Cholic acid is a primary bile acid, which triggers the germination and promotes the growth of C. difficile. The intestinal microbiota transforms primary into secondary bile acids. This study examined (1) the antimicrobial-induced alteration of fecal bile acid content, and (2) whether the concomitant administration of SB influences this transformation. This is an ancillary work from a randomized study, which revealed that SB modulates fecal microbiota dysbiosis during antibiotic treatment. Healthy subjects were randomly assigned to (1) SB only, (2) amoxicillin-clavulanate (AC), (3) SB plus AC, or (4) no treatment. We analyzed fecal concentrations of BA by high performance liquid chromatography/tandem mass spectrometry. Compared to the untreated or the SB-treated groups, AC decreased the percentage of fecal secondary BA significantly (days 3 and 7). When SB and AC were administered concomitantly, this decrease in secondary BA was no longer significant. Following treatment with AC, a significant peak of fecal CA was measured on days 3 and 7, which was prevented by the concomitant administration of SB. AC administered to healthy volunteers altered the microbial transformation of primary BA, decreased secondary BA, and increased CA. The latter was prevented by the concomitant administration of SB and AC, suggesting a potent mechanism protection conferred by SB against post-antimicrobial C. difficile infection.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01473368.

Saccharomyces boulardii CNCM I-745 - the medicinal yeast improves intestinal enzyme function

Saccharomyces boulardii CNCM I-745 is a probiotic medicinal yeast used in the prevention and treatment of diarrhea. It has numerous effects, i. a. immunological and antitoxin effects, it binds pathogens and has a beneficial effect on the intestinal microbiota. In addition, pronounced trophic effects were detected. The focus of this review is on the effects of S. boulardii CNCM I-745 on digestive enzymes located in the brush border membrane. An important role in this context is attributed to polyamines which are synthesized and secreted by S. boulardii CNCM I-745. Polyamines are essential for cell proliferation and differentiation. They enhance the expression of intestinal enzymes as well as nutrient transport systems and directly influence the nucleic acid binding capacity. S. boulardii CNCM I-745 induces signals via mitogen-activated protein kinase cascades (MAP kinase pathway) and influences the PI3 kinase signaling pathway. Furthermore, S. boulardii CNCM I-745 secretes certain enzymes that promote nutrient delivery to both the yeast itself and the host organism. The increased presence of digestive enzymes obviously contributes significantly to the clinical effect of S. boulardii CNCM I-745.

Beneficial effects of Saccharomyces boulardii CNCM I-745 on clinical disorders associated with intestinal barrier disruption.

Intestinal barrier defects lead to “leaky gut syndrome”, defined as an increase in intestinal permeability that allows the passage of luminal content into intestinal tissue and the bloodstream. Such a compromised intestinal barrier is the main factor underlying the pathogenesis of inflammatory bowel disease, but also commonly occurs in various systemic diseases such as viral infections and metabolic syndrome. The non-pathogenic yeast Saccharomyces boulardii CNCM I-745 has demonstrated its effectiveness as a probiotic in the prevention and treatment of antibiotic-associated, infectious and functional diarrhea. Via multiple mechanisms of action implicated in intestinal barrier function, S. boulardii has beneficial effects on altered intestinal microbiota and epithelial barrier defects in different pathologies. The well-studied probiotic yeast S. boulardii plays a crucial role in the preservation and/or restoration of intestinal barrier function in multiple disorders. This could be of major interest in diseases characterized by alterations in intestinal barrier function.

Saccharomyces boulardii CNCM I-745 plus sequential therapy for Helicobacter pylori infections: a randomized, open-label trial.

To determine the effect of Saccharomyces boulardii CNCM I-745 (S. boulardii) plus sequential therapy on Helicobacter pylori (H. pylori) eradication rate. This open-label prospective study randomized (1:1) patients with confirmed H. pylori infection to standard sequential therapy of twice-daily (bid) omeprazole 20mg plus amoxicillin 1g for 5days, followed by bid omeprazole 20mg, clarithromycin 500mg and metronidazole 500mg for the next 5days (control group), or sequential therapy plus bid S. boulardii 250mg (experimental group). Adverse events (AEs) were recorded throughout the study, and the H. pylori eradication rate was determined 4weeks after treatment. The study was conducted from May 2013 to May 2016 and included 199 patients (51.3% male; mean age 44.6 ± 13.6years). The H. pylori eradication rate was higher in the experimental group than the control group (86.0% vs. 74.7%; P =0.02). Compared with the control group, patients in the experimental group experienced a significantly lower overall incidence of AEs (17.0% vs. 55.7%; p < 0.001) and the incidence of antibiotic-associated diarrhea (2.0% vs. 46.4%; P = 0.02). The experimental group showed improved treatment compliance over the 10-day study period compared with the control group (95.0% vs. 91.2%, P < 0.001). Addition of S. boulardii to sequential therapy improved H. pylori eradication rate and reduced the incidence of treatment-associated AEs in Moroccan patients with H. pylori infection.

Are probiotics and prebiotics effective in the prevention of travellers' diarrhea: A systematic review and meta-analysis.

Travellers' diarrhea (TD) impacts annually over 20 million tourists, business travellers and military troops on a worldwide basis. Reliance on antibiotic prophylaxis and educational programs has not lead to a significant reduction in TD rates. Previous reviews of probiotics for TD have not accounted for the strain-specificity of probiotic efficacy nor have investigated prebiotics for the prevention of TD. Standard literature databases were searched from 1977 to June 2018 unrestricted by language. Inclusion criteria included: Probiotic, probiotic or symbiotic interventions, randomized, controlled clinical trials (RCTs) and ≥2 RCTs with the same probiotic strain or mixture. Of 158 screened articles, 12 RCT were included in the systematic review and 6 RCTs (with nine treatment different arms) were included in the meta-analysis. Saccharomyces boulardii CNCM I-745 showed a significant reduction in TD incidence (RR = 0.79, 95% C.I. 0.72-0.87, p < 0.001), while L. rhamnosus GG showed a trend (p = 0.08) and L. acidophilus showed no significant (p = 0.16) reduction of TD. The number of trials using probiotics or prebiotics for the prevention of TD continues to be limited in number. Only one of three probiotics showed significant efficacy for the prevention of TD. More research is needed for other probiotics strains and prebiotics to determine if they could also prevent TD.

Enterobacteriaceae are essential for the modulation of colitis severity by fungi

BackgroundHost-microbe balance maintains intestinal homeostasis and strongly influences inflammatory conditions such as inflammatory bowel diseases (IBD). Here we focused on bacteria-fungi interactions and their implications on intestinal inflammation, a poorly understood area.MethodsDextran sodium sulfate (DSS)-induced colitis was assessed in mice treated with vancomycin (targeting gram-positive bacteria) or colistin (targeting Enterobacteriaceae) and supplemented with either Saccharomyces boulardii CNCM I-745 or Candida albicans. Inflammation severity as well as bacterial and fungal microbiota compositions was monitored.ResultsWhile S. boulardii improved DSS-induced colitis and C. albicans worsened it in untreated settings, antibiotic treatment strongly modified DSS susceptibility and effects of fungi on colitis. Vancomycin-treated mice were fully protected from colitis, while colistin-treated mice retained colitis phenotype but were not affected anymore by administration of fungi. Antibacterial treatments not only influenced bacterial populations but also had indirect effects on fungal microbiota. Correlations between bacterial and fungal relative abundance were dramatically decreased in colistin-treated mice compared to vancomycin-treated and control mice, suggesting that colistin-sensitive bacteria are involved in interactions with fungi. Restoration of the Enterobacteriaceae population by administrating colistin-resistant Escherichia coli reestablished both beneficial effects of S. boulardii and pathogenic effects of C. albicans on colitis severity. This effect was at least partly mediated by an improved gut colonization by fungi.ConclusionsFungal colonization of the gut is affected by the Enterobacteriaceae population, indirectly modifying effects of mycobiome on the host. This finding provides new insights into the role of inter-kingdom functional interactions in intestinal physiopathology and potentially in IBD.

Time Series Analysis of the Microbiota of Children Suffering From Acute Infectious Diarrhea and Their Recovery After Treatment.

Gut microbiota is closely related to acute infectious diarrhea, one of the leading causes of mortality and morbidity in children worldwide. Understanding the dynamics of the recovery from this disease is of clinical interest. This work aims to correlate the dynamics of gut microbiota with the evolution of children who were suffering from acute infectious diarrhea caused by a rotavirus, and their recovery after the administration of a probiotic, Saccharomyces boulardii CNCM I-745. The experiment involved 10 children with acute infectious diarrhea caused by a rotavirus, and six healthy children, all aged between 3 and 4 years. The children who suffered the rotavirus infection received S. boulardii CNCM I-745 twice daily for the first 5 days of the experiment. Fecal samples were collected from each participant at 0, 3, 5, 10, and 30 days after probiotic administration. Microbial composition was characterized by 16S rRNA gene sequencing. Alpha and beta diversity were calculated, along with dynamical analysis based on Taylor's law to assess the temporal stability of the microbiota. All children infected with the rotavirus stopped having diarrhea at day 3 after the intervention. We observed low alpha diversities in the first 5 days (p-value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic treatment. Canonical correspondence analysis (CCA) showed differences in the gut microbiota of healthy children and of those who suffered from acute diarrhea in the first days (p-value < 0.05, ADONIS test), but not in the last days of the experiment. Temporal variability was larger in children infected with the rotavirus than in healthy ones. In particular, Gammaproteobacteria class was found to be abundant in children with acute diarrhea. We identified the microbiota transition from a diseased state to a healthy one with time, whose characterization may lead to relevant clinical data. This work highlights the importance of using time series for the study of dysbiosis related to diarrhea.

Strain-Specificity and Disease-Specificity of Probiotic Efficacy: A Systematic Review and Meta-Analysis.

As the use and diversity of probiotic products expands, the choice of an appropriate type of probiotic is challenging for both medical care professionals and the public alike. Two vital factors in choosing the appropriate probiotic are often ignored, namely, the probiotic strain-specificity and disease-specificity for efficacy. Reviews and meta-analyses often pool together different types of probiotics, resulting in misleading conclusions of efficacy. A systematic review of the literature (1970-2017) assessing strain-specific and disease-specific probiotic efficacy was conducted. Trials were included for probiotics with an identifiable strain (either single strain or mixtures of strains) that had at least two randomized, controlled trials for each type of disease indication. The goal was to determine if probiotic strains have strain and/or disease-specific efficacy. We included 228 trials and found evidence for both strain specificity and disease specificity for the efficacy of specific probiotic strains. Significant efficacy evidence was found for 7 (70%) of probiotic strain(s) among four preventive indications and 11 (65%) probiotic strain(s) among five treatment indications. Strain-specific efficacy for preventing adult antibiotic-associated diarrhea was clearly demonstrated within the Lactobacillus species [e.g., by the mixture of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+®), by L. casei DN114001 (Actimel®) and by Lactobacillus reuteri 55730], while other Lactobacillus strains did not show efficacy. Significant disease-specific variations in efficacy was demonstrated by L. rhamnosus GG and Saccharomyces boulardii CNCM I-745, as well as other probiotic strains. Strong evidence was found supporting the hypothesis that the efficacy of probiotics is both strain-specific and disease-specific. Clinical guidelines and meta-analyses need to recognize the importance of reporting outcomes by both specific strain(s) of probiotics and the type of disease. The clinical relevance of these findings indicates that health-care providers need to take these two factors into consideration when recommending the appropriate probiotic for their patient.

Oral Administration of Recombinant Saccharomyces boulardii Expressing Ovalbumin-CPE Fusion Protein Induces Antibody Response in Mice.

Saccharomyces boulardii, a subspecies of Saccharomyces cerevisiae, is a well-known eukaryotic probiotic with many benefits for human health. In the present study, a recombinant strain of S. boulardii was prepared to use as a potential oral vaccine delivery vehicle. In this sense, a ura3 auxotroph strain of S. boulardii CNCM I-745 (known as S. cerevisiae HANSEN CBS 5926, Yomogi®) was generated using CRISPR/Cas9 methodology. Then a gene construct encoding a highly immunogenic protein, ovalbumin (OVA), was prepared and transformed into the ura3- S. boulardii. To facilitate the transport of the recombinant immunogen across the intestinal barrier, a claudin-targeting sequence from Clostridium perfringens enterotoxin (CPE) was added to the C-terminus of the expression cassette. The recombinant S. boulardii strain expressing the OVA-CPE fusion protein was then administered orally to a group of mice, and serum IgG and fecal IgA levels were evaluated by ELISA. Our results demonstrated that anti-OVA IgG in serum significantly increased in test group (P < 0.001) compared to control groups (receiving wild type S. boulardii or PBS), and the fecal IgA titer was significantly higher in test group (P < 0.05) than control groups. In parallel, a recombinant S. boulardii strain expressing the similar construct lacking C-terminal CPE was also administered orally. The result showed an increased level of serum IgG in group receiving yeasts expressing the CPE negative construct compared to control groups; however, the fecal IgA levels did not increase significantly. In conclusion, our findings indicated that the yeast S. boulardii, as a delivery vehicle with possible immunomodulatory effects, and c-CPE, as a targeting tag, synergistically assist to stimulate systemic and local immunity. This proposed recombinant S. boulardii system might be useful in the expression of other antigenic peptides, making it as a promising tool for oral delivery of vaccines or therapeutic proteins.

Saccharomyces boulardii CNCM I-745 Improves Intestinal Enzyme Function: A Trophic Effects Review.

Several properties of the probiotic medicinal yeast Saccharomyces boulardii CNCM I-745 contribute to its efficacy to prevent or treat diarrhoea. Besides immunologic effects, pathogen-binding and anti-toxin effects, as well as positive effects on the microbiota, S boulardii CNCM I-745 also has pronounced effects on digestive enzymes of the brush border membrane, known as trophic effects. The latter are the focus of this review. Literature has been reviewed after searching Medline and PMC databases. All relevant non-clinical and clinical studies are summarized. S. boulardii CNCM I-745 synthesizes and secretes polyamines, which have a role in cell proliferation and differentiation. The administration of polyamines or S. boulardii CNCM I-745 enhances the expression of intestinal digestive enzymes as well as nutrient uptake transporters. The signalling mechanisms leading to enzyme activation are not fully understood. However, polyamines have direct nucleic acid–binding capacity with regulatory impact. S. boulardii CNCM I-745 induces signalling via the mitogen-activated protein kinase pathway. In addition, effects on the phosphatidylinositol-3 kinase (PI3K) pathway have been reported. As an additional direct effect, S. boulardii CNCM I-745 secretes certain enzymes, which enhance nutrient acquisition for the yeast and the host. The increased availability of digestive enzymes seems to be one of the mechanisms by which S. boulardii CNCM I-745 counteracts diarrhoea; however, also people with certain enzyme deficiencies may profit from its administration. More studies are needed to fully understand the mechanisms of trophic activation by the probiotic yeast.

Probiotics for gastrointestinal disorders: Proposed recommendations for children of the Asia-Pacific region.

Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG (LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile-induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic (L reuteri) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials.