Saccharomyces cerevisiae I-3856 in irritable bowel syndrome with predominant constipation.

BACKGROUND: Probiotics are a promising solution for managing irritable bowel syndrome (IBS). Saccharomyces cerevisiae (S. cerevisiae) I-3856 has already demonstrated beneficial effects in IBS subjects, particularly in IBS with predominant constipation (IBS-C). AIM: To confirm the efficacy of S. cerevisiae I-3856 in the management of gastrointestinal symptoms in IBS-C. METHODS: A randomized, double-blind, placebo-controlled clinical study was performed in a total of 456 subjects. After a run-in period, subjects were randomly assigned to the group receiving S. cerevisiae I-3856 (8 × 109 CFU daily) or the placebo for 8 wk, and they performed daily self-evaluations of gastrointestinal symptoms. The primary objective was to assess the effect of the probiotic on abdominal pain. The secondary objectives were the evaluation of other gastrointestinal symptoms, bowel movement frequency and consistency, and quality of life (QOL). RESULTS: A significantly higher proportion of abdominal pain responders was reported in the Probiotic group (45.1% vs 33.9%, P = 0.017). A nonsignificant difference in the area under the curve for abdominal pain over the second month of supplementation was observed in subjects receiving probiotic vs placebo [P = 0.073, 95%CI: -0.59 (-1.23; 0.05)]. No statistically significant differences were reported in the evolution of bowel movement frequency and stool consistency between the groups. After 8 wk of supplementation, the overall QOL score was significantly higher in the Probiotic group than in the Placebo group [P = 0.047, 95%CI: 3.86 (0.52; 7.20)]. Furthermore, exploratory analyses showed statistically significant and clinically relevant improvements in QOL scores in abdominal pain responders vs nonresponders. CONCLUSION: The results of this clinical study confirmed the abdominal pain alleviation properties of S. cerevisiae I-3856 in IBS-C. Abdominal pain relief was associated with improved QOL. ClinicalTrials.gov identifier: NCT03150212.

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Saccharomyces boulardii in Infants and Children With Acute Diarrhea.

AIM: This study was designed to assess the efficacy and safety of Saccharomyces cerevisiae variant boulardii CNCM I-3799 (S. boulardii CNCM I-3799) in the management of acute diarrhea in children. METHODS: A total of 100 infants and children 3-36 months of age with acute diarrhea received medical care according to the World Health Organization guidelines on the management of acute diarrhea in children and were randomly allocated to the probiotic group (S. boulardii CNCM I-3799 at a daily dose of 5 billion CFU twice daily) or to the placebo group. Infants and children were treated for 5 days and an extended follow-up was planned 1 and 2 months after the end of the treatment period. Primary endpoint was the time of recovery from diarrhea defined as the duration of diarrhea. Other parameters, such as frequency and consistency of stools, associated with the severity of diarrhea episodes were defined as secondary endpoints. RESULTS: The administration of S. boulardii CNCM I-3799 was associated with beneficial effects on duration and severity of diarrhea. The time of recovery from diarrhea was significantly shorter in the probiotic group compared with the placebo group (65.8 ± 12 hours vs. 95.3 ± 17.6 hours, P = 0.0001). Faster remission in the probiotic group was also demonstrated by a shorter time before the first episode of semisolid stool [-23.5 hours, diff (95% CI): -7.99 (-31.49 to -15.51), P = 0.0001] and the faster normalization of stool consistency. S. boulardii CNCM I-3799 was well tolerated. CONCLUSION: S. boulardii CNCM I-3799 supplementation in children with acute diarrhea was shown effective in reducing the duration and severity of diarrhea in infants and children.

Anti-Biofilm Properties of Saccharomyces cerevisiae CNCM I-3856 and Lacticaseibacillus rhamnosus ATCC 53103 Probiotics against G. vaginalis.

Bacterial vaginosis (BV) is characterized by the presence of a polymicrobial biofilm where Gardnerella vaginalis plays a key role. Previously, we demonstrated that Saccharomyces cerevisiae CNCM (French National Collection of Cultures of Microorganisms) I-3856 is helpful in resolving experimental simulated BV in mice. In this study, we analyzed its capacity to affect G. vaginalis biofilms and to potentiate the activity of standard antimicrobial agents. We also investigated the anti-biofilm activity of Lacticaseibacillus rhamnosus GG (ATCC 53103), a well-known strain for its intestinal healthy benefits. Biofilm biomass was assessed by crystal violet staining, and G. vaginalis viability was assessed by a colony forming unit (CFU) assay. Here, for the first time, we demonstrated that S. cerevisiae CNCM I-3856 as well as L. rhamnosus GG were able (i) to significantly inhibit G. vaginalis biofilm formation, (ii) to markedly reduce G. vaginalis viability among the biomass constituting the biofilm, (iii) to induce disaggregation of preformed biofilm, and (iv) to kill a consistent amount of bacterial cells in a G. vaginalis preformed biofilm. Furthermore, S. cerevisiae CNCM I-3856 strongly potentiates the metronidazole effect on G. vaginalis biofilm viability. These results suggest that S. cerevisiae CNCM I-3856 as well as L. rhamnosus GG could be potential novel therapeutic agents against bacterial vaginosis.

Recovery of Saccharomyces cerevisiae CNCM I-3856 in Vaginal Samples of Healthy Women after Oral Administration.

Bacterial vaginosis and vulvovaginal candidiasis are common causes of impaired health and quality of life for women. Although antimicrobial agents remain the main strategy for the treatment of vaginal infections, their repeated use involves high rates of resistance and recurrence. Alternative approaches such as probiotics are studied. Saccharomyces cerevisiae CNCM I-3856 already demonstrated beneficial effects in experimental models of vaginal infections. This randomized, double-blind, placebo-controlled clinical study was performed to evaluate the recovery of S. cerevisiae CNCM I-3856 in vaginal samples in healthy women after oral consumption. Sixty healthy women were randomized to receive a daily dose of S. cerevisiae CNCM I-3856 or a placebo for 4 weeks. Subcultures and quantitative polymerase chain reaction (qPCR) were used to detect the strain in vaginal and stool samples. A safety assessment was carried out throughout the study. Fifty-seven women completed the study. Over the 4-week supplementation phase, S. cerevisiae CNCM I-3856 has been detected in the vaginal samples of 21% of women (n = 4/19) in the 500 mg Probiotic group and 16% of women (n = 3/19) in the 1000 mg Probiotic group. The strain was detected in the faeces of 90% of women consuming the probiotic. This is the first clinical study demonstrating the migration of yeast from intestine to vagina where it may exert its benefits.

Saccharomyces cerevisiae CNCM I-3856 as a New Therapeutic Agent Against Oropharyngeal Candidiasis.

Oropharyngeal candidiasis is a common opportunistic mucosal infection of the oral cavity, mainly caused by an overgrowth of Candida albicans. This infection can inhibit nutritional intakes and strongly affect quality of life. To date, standard therapeutic strategies involving the administration of antifungal drugs can bring several side effects, not least the emergence of drug-resistant strains. The purpose of this study is to investigate the effectiveness of Saccharomyces cerevisiae CNCM I-3856 (live or inactivated cells) against oropharyngeal candidiasis. Our results show that administration of S. cerevisiae CNCM I-3856 (live or inactivated cells) in the oral cavity of C57BL/6J mice resulted in a protective effect against oropharyngeal candidiasis. The strongest effect was obtained with live S. cerevisiae CNCM I-3856. This was related to: (1) a decrease in C. albicans load in the oral cavity, esophagus, stomach, and duodenum; (2) an early resolution of inflammatory process in the tongue; (3) a marked reduction in C. albicans virulence factors; and (4) a consistent increase in neutrophil antimicrobial capacity. These findings suggest that S. cerevisiae products are potentially beneficial in the treatment of oropharyngeal candidiasis.

Saccharomyces cerevisiae-based probiotic as novel anti-microbial agent for therapy of bacterial vaginosis.

In this study, we demonstrate, for the first time, that Saccharomyces cerevisiae-based probiotic shows an inhibitory effect on Gardnerella vaginalis infection. This effect is likely due to several actions: direct interference with adherence to vaginal tissues, inhibition of sialidase activity, reduction of vaginal epithelial exfoliation. Gardnerella vaginalis does not induce vaginal inflammation and no inflammatory cytokines were, indeed, produced, by the mouse vagina, neither by Gardnerella vaginalis and by the probiotic. Collectively, our data incite to further investigations on Saccharomyces cerevisiae probiotic as a potential prophylactic or therapeutic agent in the vaginosis caused by Gardnerella vaginalis.

Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: An individual subject meta-analysis.

AIM: To confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) management. METHODS: An individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal (GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve (AUC) and weekly means], responder status, and bowel movements (stool frequency and consistency). Statistical analyses were conducted in Intent to Treat (ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline ("IBS-C ≥ 2 subpopulation"). RESULTS: S. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AUC (W5-W8)] with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group (P = 0.0134) has been observed. In the IBS-C ≥ 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group (P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit (a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder (reduction of 1 a.u. of abdominal pain/discomfort) compared with subjects in the Placebo group (P = 0.0240). At the end of supplementation period, stool consistency in the Active group of the ITT population was significantly improved and classified as "normal" compared to Placebo (respectively 3.13 ± 1.197 a.u. vs 2.58 ± 1.020 a.u., P = 0.0003). Similar results were seen in the IBS-C ≥ 2 subpopulation (Active group: 3.14 ± 1.219 a.u. vs Placebo group: 2.59 ± 1.017 a.u., P = 0.0009). CONCLUSION: This meta-analysis supports previous data linking S. cerevisiae I-3856 and improvement of GI symptoms, in IBS overall population and in the IBS-C and IBS-C ≥ 2 subpopulations.

Therapeutic activity of a Saccharomyces cerevisiae-based probiotic and inactivated whole yeast on vaginal candidiasis.

Vulvovaginal candidiasis is the most prevalent vaginal infection worldwide and Candida albicans is its major agent. Vulvovaginal candidiasis is characterized by disruption of the vaginal microbiota composition, as happens following large spectrum antibiotic usage. Recent studies support the effectiveness of oral and local probiotic treatment for prevention of recurrent vulvovaginal candidiasis. Saccharomyces cerevisiae is a safe yeast used as, or for, the production of ingredients for human nutrition and health. Here, we demonstrate that vaginal administration of probiotic Saccharomyces cerevisiae live yeast (GI) and, in part, inactivated whole yeast Saccharomyces cerevisiae (IY), used as post-challenge therapeutics, was able to positively influence the course of vaginal candidiasis by accelerating the clearance of the fungus. This effect was likely due to multiple interactions of Saccharomyces cerevisiae with Candida albicans. Both live and inactivated yeasts induced coaggregation of Candida and consequently inhibited its adherence to epithelial cells. However, only the probiotic yeast was able to suppress some major virulence factors of Candida albicans such as the ability to switch from yeast to mycelial form and the capacity to express several aspartyl proteases. The effectiveness of live yeast was higher than that of inactivated whole yeast suggesting that the synergy between mechanical effects and biological effects were dominant over purely mechanical effects. The protection of epithelial cells to Candida-induced damage was also observed. Overall, our data show for the first time that Saccharomyces cerevisiae-based ingredients, particularly the living cells, can exert beneficial therapeutic effects on a widespread vaginal mucosal infection.

Randomized double blind placebo-controlled trial of Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: improvement in abdominal pain and bloating in those with predominant constipation.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and/or discomfort. Probiotics have been reported to benefit IBS symptoms but the level of benefit remains quite unclear. OBJECTIVE: This study was designed to assess the benefit of Saccharomyces cerevisiae I-3856 on IBS symptoms. METHODS: A randomized, double blind, placebo-controlled trial has been performed in 379 subjects with diagnosed IBS. Subjects were randomly supplemented with the probiotics (1000 mg) or placebo for 12 weeks. Questionnaires (gastrointestinal symptoms, stools, wellbeing, and quality of life) were completed. Primary endpoint was percentage of responders defined as having a 50% decrease in the weekly average "intestinal pain/discomfort score" for at least 4 out of the last 8 weeks of the study. RESULTS: There was no overall benefit of S. cerevisiae I-3856 on IBS symptoms and wellbeing in the study population. Moreover, S. cerevisiae I-3856 was not statistically significant predictor of the responder status of the subjects (p > 0.05). Planned subgroup analyses showed significant effect in the IBS-C subjects: improvement of gastrointestinal symptoms was significantly higher in active group, compared to placebo, on abdominal pain/discomfort and bloating throughout the study and at the end of the supplementation. CONCLUSIONS: In this study, S. cerevisiae I-3856 at the dose of 1000 mg per day does not improve intestinal pain and discomfort in general IBS patients. However, it seems to have an effect in the subgroup with constipation which needs further studies to confirm (NCT01613456 in ClinicalTrials.gov registry).