Enhancing probiotic impact: engineering Saccharomyces boulardii for optimal acetic acid production and gastric passage tolerance.

Saccharomyces boulardii has been a subject of growing interest due to its potential as a probiotic microorganism with applications in gastrointestinal health, but the molecular cause for its probiotic potency has remained elusive. The recent discovery that S. boulardii contains unique mutations causing high acetic acid accumulation and inhibition of bacterial growth provides a possible clue. The natural S. boulardii isolates Sb.P and Sb.A are homozygous for the recessive mutation whi2S270* and accumulate unusually high amounts of acetic acid, which strongly inhibit bacterial growth. However, the homozygous whi2S270* mutation also leads to acetic acid sensitivity and acid sensitivity in general. In the present study, we have constructed a new S. boulardii strain, derived from the widely therapeutically used CMCN I-745 strain (isolated from the pharmaceutical product Enterol), producing even higher levels of acetic acid while keeping the same tolerance toward low pH as the parent Enterol (ENT) strain. This newly engineered strain, named ENT3, has a homozygous deletion of ACH1 and strong overexpression of ALD4. It is also able to accumulate much higher acetic acid concentrations when growing on low glucose levels, in contrast to the ENT wild-type and Sb.P strains. Moreover, we show the antimicrobial capacity of ENT3 against gut pathogens in vitro and observed that higher acetic acid production might correlate with better persistence in the gut in healthy mice. These findings underscore the possible role of the unique acetic acid production and its potential for improvement of the probiotic action of S. boulardii.IMPORTANCESuperior variants of the probiotic yeast Saccharomyces boulardii produce high levels of acetic acid, which inhibit the growth of bacterial pathogens. However, these strains also show increased acid sensitivity, which can compromise the viability of the cells during their passage through the stomach. In this work, we have developed by genetic engineering a variant of Saccharomyces boulardii that produces even higher levels of acetic acid and does not show enhanced acid sensitivity. We also show that the S. boulardii yeasts with higher acetic acid production persist longer in the gut, in agreement with a previous work indicating competition between probiotic yeast and bacteria for residence in the gut.

Formulation of a probiotic product using Almond gum.

BACKGROUND: The application of probiotics in food has expanded significantly, yet its viability remains a challenge. In response to this issue, this study explores a unique approach. Almond gum, a natural extract from Prunus dulcis, is utilized as the primary carrier matrix for a novel probiotic product featuring Saccharomyces boulardii, a probiotic yeast. METHODS: This study involves the entrapment of S. boulardii in almond gum through centrifugation (5 min at 1300 × g) and subsequent 24 h drying at 50 °C. Sensory evaluation and other investigations were conducted at different pH levels to assess viability and performance. RESULTS: Post-drying entrapment efficiency was 83.85%, underscoring the benefits of choosing almond gum as a carrier matrix. Promising results were observed from viability testing conducted in gastric juice (pH 1.2) and in simulated intestinal fluid (pH 6.8). Matrix stability was assessed by measuring cfu ml-1 following 7 days' storage at different temperatures, complemented by sensory analysis. CONCLUSION: Almond gum is a promising carrier matrix for probiotic products. Its high entrapment efficiency and its viability under challenging pH conditions demonstrate its efficacy. It is rich in carbohydrates and serves a dual purpose by acting as a prebiotic source, as confirmed through ultraviolet-visible (UV-visible) analysis. The study underscores the potential of this novel approach, providing insights into responses to viability challenges in probiotic food products. © 2024 Society of Chemical Industry.

Evaluation of the impact of polypeptide-p on diabetic rats upon its cloning, expression, and secretion in Saccharomyces boulardii.

This study was designed to evaluate the effectiveness of recombinant polypeptide-p derived from Momordica charantia on diabetic rats. In this research, the optimized sequence of polypeptide-p gene fused to a secretion signal tag was cloned into the expression vector and transformed into probiotic Saccharomyces boulardii. The production of recombinant secretion protein was verified by western blotting, HPLC, and mass spectrometry. To assay recombinant yeast bioactivity in the gut, diabetic rats were orally fed wild-type and recombinant S. boulardii, in short SB and rSB, respectively, at two low and high doses as well as glibenclamide as a reference drug. In untreated diabetic and treated diabetic + SB rats (low and high doses), the blood glucose increased from 461, 481, and 455 (mg/dl), respectively, to higher than 600 mg/dl on the 21st day. Whereas glibenclamide and rSB treatments showed a significant reduction in the blood glucose level. The result of this study promised a safe plant-source supplement for diabetes through probiotic orchestration.

The effect of Saccharomyces boulardii supplementation on Helicobacter pylori eradication in children: a systematic review and meta-analysis of Randomized controlled trials.

BACKGROUND: It is unclear whether Saccharomyces boulardii (S. boulardii) supplementation in standard triple therapy (STT) is effective in eradicating Helicobacter pylori (H. pylori) infection in children. We therefore conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effect of S. boulardii supplementation on H. pylori eradication in children. METHODS: We conducted electronic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure and Wanfang database from the beginning up to September 2023. A random-effects model was employed to calculate the pooled relative risk (RR) with 95% confidence intervals (CI) through a meta-analysis. RESULTS: Fifteen RCTs (involving 2156 patients) were included in our meta-analysis. Results of the meta-analysis indicated that S. boulardii in combination with STT was more effective than STT alone (intention-to-treat analysis : 87.7% vs. 75.9%, RR = 1.14, 95% CI: 1.10-1.19, P < 0.00001; per-protocol analysis : 88.5% vs. 76.3%, RR = 1.15, 95% CI: 1.10-1.19, P < 0.00001). The S. boulardii supplementation group had a significantly lower incidence of total adverse events (n = 6 RCTs, 9.2% vs. 29.2%, RR = 0.32, 95% CI: 0.21-0.48, P < 0.00001), diarrhea (n = 13 RCTs, 14.7% vs. 32.4%, RR = 0.46, 95% CI: 0.37-0.56, P < 0.00001), and nausea (n = 11 RCTs, 12.7% vs. 21.3%, RR = 0.53, 95% CI: 0.40-0.72, P < 0.0001) than STT group alone. Similar results were also observed in the incidence of vomiting, constipation, abdominal pain, abdominal distention, epigastric discomfort, poor appetite and stomatitis. CONCLUSIONS: Current evidence indicated that S. boulardii supplementing with STT could improve the eradication rate of H. pylori, and concurrently decrease the incidence of total adverse events and gastrointestinal adverse events in children.

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori: Current perspectives and implications.

Yu et al's study in the World Journal of Gastroenterology (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii (S. boulardii) for the rescue therapy against Helicobacter pylori (H. pylori), a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H+/K+-ATPase pump, Vonoprazan competes with the K+ ions, prevents the ions from binding to the pump and blocks acid secretion. Concerns with increasing antibiotic resistance, effects on the gut microbiota, patient compliance, and side effects have led to the advent of a dual regimen for H. pylori. Previous studies suggested that S. boulardii plays a role in stabilizing the gut barrier which improves H. pylori eradication rate. With an acceptable safety profile, the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile, thereby strengthening the applicability in clinical settings. Nonetheless, S. boulardii comes in various formulations and dosages, warranting further exploration into the optimal dosage for supplementation in rescue therapy. Additionally, larger, randomized, double-blinded controlled trials are warranted to confirm these promising results.

The preventive effects of Saccharomyces boulardii against oxidative stress induced by lipopolysaccharide in rat brain.

The brain is sensitive to oxidative stress, which can trigger microglial activation and neuroinflammation. Antioxidant therapies may provide neuroprotection against oxidative stress. In recent years antioxidant effects of probiotics and their possible mechanisms in oxidative stress-related models have been determined. In the current study, for the first time, we assessed the effects of Saccharomyces boulardii on oxidative stress provoked by lipopolysaccharide (LPS) in the rat brain. Four groups of animals were used, including the control, LPS, S. boulardii + LPS, and S. boulardii groups. All animals received either saline or S. boulardii (1010 CFU) by gavage for four weeks. Between days 14 and 22, all animals received either LPS (250 µg/kg) or saline by intraperitoneal (i.p.) injection. S. boulardii was able to inhibit lipid peroxidation and prevent the reduction of antioxidant levels, including glutathione and catalase in the model of oxidative stress induced by LPS in the rat hippocampus and cortex. Also, it increased the lowered ratio of glutathione/oxidized glutathione in both tissues. Serum levels of anti-inflammatory interleukin 10 (IL-10) and proinflammatory cytokines IL-6 and IL-8 increased and decreased, respectively. S. boulardii has potential antioxidant activities in oxidative stress-related model, possibly modulating gut microbiota, immune defense, and antioxidant enzyme activities that can be considered in preventing oxidative stress-related central nervous system (CNS) diseases.

Saccharomyces boulardii combined with triple therapy alter the microbiota in the eradication of Helicobacter pylori infection.

To assess the effectiveness and safety of combining Saccharomyces boulardii powder with triple therapy as a primary approach for eradicating H. pylori infection, a total of 144 patients who tested positive for H. pylori and diagnosed with non-ulcer dyspepsia underwent endoscopy at two national centers between June 2017 and March 2019 were included. The patients were categorized into three groups using a subsection randomization method and received initial H. pylori eradication treatments. Microbial composition, eradication rates, symptom alleviation, and adverse reactions were monitored on the 14th and 44th days post-treatment. According to PP analysis showed the eradication rates for the SRAC group was 75%, BRAC was 93.18% and RAC was 65.2%. Group BRAC exhibited a marginally higher eradication rate compared to other groups. However, patients receiving Saccharomyces boulardii treatment exhibited an overall reduction in initial dyspepsia symptoms by the end of the treatment period. When employed as a primary strategy, the combination of Saccharomyces boulardii powder with triple therapy displayed notable efficacy and smaller gastrointestinal side effects in eradicating initial H. pylori infections among non-ulcer dyspepsia patients. Moreover, this approach demonstrated advantages in alleviating symptoms, exhibited favorable tolerance, and maintained a high level of clinical safety.

Intervention with fructooligosaccharides, Saccharomyces boulardii, and their combination in a colitis mouse model.

Objective: To examine the effects of an intervention with fructooligosaccharides (FOS), Saccharomyces boulardii, and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects. Methods: The effects of FOS, S. boulardii, and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition. Results: FOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, S. boulardii could significantly reduced the DAI, inhibited the production of IL-1ß, and prevented colon shortening. Nevertheless, S. boulardii treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/S. boulardii resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/S. boulardii combination (109 CFU/ml and 107 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1ß and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/S. boulardii 109 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/S. boulardii 107 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and S. boulardii significantly increased the abundance of Parabacteroides and decreased the abundance of Escherichia-Shigella. Additionally, it promoted the production of acetic acid and propionic acid. Conclusion: Compared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as lactobacilli and Bifidobacteria and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/S. boulardii combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and S. boulardii.

Saccharomyces Boulardii alleviates neuroinflammation and oxidative stress in PTZ-kindled seizure rat model.

Previous research have reported that modulating the gut microbiome composition by fecal microbiota transplantation and probiotic administration can alleviate seizure occurrence and severity. Saccharomyces boulardii (SB) is a yeast probiotic that has demonstrated ameliorating effects on anxiety, memory and cognitive deficit, and brain amyloidogenesis. In this research, our goal was to examine the anti-seizure effects of SB on the pentylenetetrazole (PTZ)-kindled male Wistar rats. The animals were randomly categorized into four test groups. The rats were orally administered with saline (control and PTZ groups) or S. boulardii (SB + PTZ and SB groups) for 57 days. From the 29th day of the experiment, the animals received intraperitoneally saline (control and SB groups) or PTZ (PTZ and SB + PTZ groups) on alternate days for 30 days. The administration dose of SB and PTZ was 1010 CFU/ml/day and 35 mg/kg, respectively. We assessed animal seizure behavior, neuroinflammation, oxidative stress, and the levels of matrix metalloproteinase-9 (MMP-9) and brain-derived neurotrophic factor (BDNF) in the hippocampus tissue. S. boulardii hindered the PTZ-induced kindling development. SB treatment elevated glutathione (GSH) and total antioxidant capacity (TAC) and reduced malondialdehyde (MDA) levels. SB also lessened the hippocampal levels of BDNF and MMP-9. Following SB supplementation, proinflammatory cytokines interleukin-1 beta (IL-1ß) and IL-6 were lowered, and anti-inflammatory cytokine IL-10 was enhanced. Overall, our data indicated, for the first time, the positive impact of SB on the PTZ-kindled seizure rat model. The anti-seizure activity of SB was mediated by modulating oxidative stress, neuroinflammation, and MMP-9 and BDNF levels.

The effect of supplementing with Saccharomyces boulardii on bismuth quadruple therapy for eradicating Helicobacter pylori: a systematic review and meta-analysis of randomized controlled trials.

Background and objective: It remains uncertain if the addition of Saccharomyces boulardii (S. boulardii) to bismuth quadruple therapy (BQT) recommended in the current guidelines can enhance the Helicobacter pylori (H. pylori) eradication rate and decrease the incidence of adverse events. We therefore conducted a meta-analysis of randomized controlled trials (RCTs) to address this issue. Methods: We performed comprehensive searches in PubMed, Embase, Web of Science, and Cochrane library databases from the inception of the databases through to November 1, 2023. A meta-analysis was conducted to determine the pooled relative risk (RR) with 95% confidence intervals (CI) using a random-effects model. We utilized the revised Cochrane Risk of Bias Tool to assess the risk of bias of included studies. Results: A total of six RCTs (1,404 patients) included in this meta-analysis. The results of the intention-to-treat analysis showed that the combination of S. boulardii with BQT had a higher eradication rate than BQT alone (87.0% versus 83.3%), with a pooled RR of 1.05 (95% CI: 1.00-1.10, p = 0.03). In the per-protocol analysis, however, there was no statistical significance between the two groups in the eradication rate (93.7% versus 91.0%, RR = 1.03, 95% CI: 1.00-1.06, p = 0.07). The combination of S. boulardii and BQT had a significantly lower rate of overall adverse events (22% vs. 39%, RR = 0.56, 95% CI: 0.44-0.70, p < 0.00001), diarrhea (7.9% vs. 25.7%, RR = 0.29, 95% CI: 0.17-0.48, p < 0.00001), constipation (2.9% vs. 8.4%, RR = 0.35, 95% CI: 0.14-0.88, p = 0.03) and abdominal distention (4.9% vs. 12.7%, RR = 0.41, 95% CI: 0.23-0.72, p = 0.002) than BQT alone. For the assessment of risk of bias, five studies were deemed to have some concerns, while one study was judged to have a low risk. Conclusion: Current evidence suggests that supplementation with S. boulardii in BQT may not have a major effect on the H. pylori eradication rate, but significantly reduces the incidence of overall adverse events, diarrhea, abdominal distention and constipation. Combining S. Boulardii with BQT can help alleviate symptoms, potentially improving patient adherence. Systematic review registration: https://osf.io/n9z7c.

Harnessing probiotics capability to combat Salmonella Heidelberg and improve intestinal health in broilers.

The poultry industry faces significant challenges in controlling Salmonella contamination while reducing antibiotic use, particularly with the emergence of Salmonella Heidelberg (SH) strains posing risks to food safety and public health. Probiotics, notably lactic acid bacteria (LAB) and Saccharomyces boulardii (SB) offer promising alternatives for mitigating Salmonella colonization in broilers. Understanding the efficacy of probiotics in combating SH and their impact on gut health and metabolism is crucial for improving poultry production practices and ensuring food safety standards. This study aimed to assess the inhibitory effects of LAB and SB against SH both in vitro and in vivo broilers, while also investigating their impact on fecal metabolites and caecal microbiome composition. In vitro analysis demonstrated strong inhibition of SH by certain probiotic strains, such as Lactiplantibacillus plantarum (LP) and Lacticaseibacillus acidophilus (LA), while others like SB and Lactobacillus delbrueckii (LD) did not exhibit significant inhibition. In vivo testing revealed that broilers receiving probiotics had significantly lower SH concentrations in cecal content compared to the positive control (PC) at all ages, indicating a protective effect of probiotics against SH colonization. Metagenomic analysis of cecal-content microbiota identified predominant bacterial families and genera, highlighting changes in microbiota composition with age and probiotic supplementation. Additionally, fecal metabolomics profiling showed alterations in metabolite concentrations, suggesting reduced oxidative stress, intestinal inflammation, and improved gut health in probiotic-supplemented birds. These findings underscore the potential of probiotics to mitigate SH colonization and improve broiler health while reducing reliance on antibiotics.

Anti-Cariogenic Effects of S. cerevisiae and S. boulardii in S. mutans-C. albicans Cross-Kingdom In Vitro Models.

Despite the well-documented health benefits of the probiotic Saccharomyces, its application in oral health has not been comprehensively assessed. Dental caries is a transmissible disease initiated by acid production of cariogenic bacteria and yeast, such as Streptococcus mutans and Candida albicans, on tooth enamel and followed by subsequent enamel demineralization. Here, we investigated the effect of two Saccharomyces strains (Saccharomyces boulardii and Saccharomyces cerevisiae) on S. mutans-C. albicans cross-kingdom interactions using a cariogenic planktonic model. Viable cells, pH changes, and gene expression were measured. S. cerevisiae and S. boulardii inhibited the growth of C. albicans in dual- and multi-species conditions at 4, 6, and 20 h. Saccharomyces also inhibited C. albicans hyphal formation. Furthermore, Saccharomyces reduced the acidity of the culture medium, which usually plummeted below pH 5 when S. mutans and C. albicans were present in the model. The presence of Saccharomyces maintained the culture medium above 6 even after overnight incubation, demonstrating a protective potential against dental enamel demineralization. S. boulardii significantly down-regulated S. mutans atpD and eno gene expression. Overall, our results shed light on a new promising candidate, Saccharomyces, for dental caries prevention due to its potential to create a less cariogenic environment marked by a neutral pH and reduced growth of C. albicans.

Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.

BACKGROUND: Allergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms. METHODS: First, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16 s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3. RESULTS: S. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16 s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury. CONCLUSIONS: S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.

Heat-Killed Saccharomyces boulardii Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Restoring the Intestinal Barrier, Reducing Inflammation, and Modulating the Gut Microbiota.

Ulcerative colitis (UC) is a global intestinal disease, and conventional therapeutic drugs often fail to meet the needs of patients. There is an urgent need to find efficient and affordable novel biological therapies. Saccharomyces boulardii has been widely used in food and pharmaceutical research due to its anti-inflammatory properties and gut health benefits. However, there is still a relatively limited comparison and evaluation of different forms of S. boulardii treatment for UC. This study aimed to compare the therapeutic effects of S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan on UC, to explore the potential of heat-killed S. boulardii as a new biological therapy. The results demonstrate that all three treatments were able to restore body weight, reduce the disease activity index (DAI), inhibit splenomegaly, shorten colon length, and alleviate histopathological damage to colonic epithelial tissues in DSS-induced colitis mice. The oral administration of S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan also increased the levels of tight junction proteins (Occludin and ZO-1), decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the serum, and suppressed the expressions of TNF-α, IL-1ß, and IL-6 mRNA in the colon. In particular, in terms of gut microbiota, S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan exhibited varying degrees of modulation on DSS-induced dysbiosis. Among them, heat-killed S. boulardii maximally restored the composition, structure, and functionality of the intestinal microbiota to normal levels. In conclusion, heat-killed S. boulardii showed greater advantages over S. boulardii and S. boulardii ß-glucan in the treatment of intestinal diseases, and it holds promise as an effective novel biological therapy for UC. This study is of great importance in improving the quality of life for UC patients and reducing the burden of the disease.

Production of iron enriched Saccharomyces boulardii: impact of process variables.

About half of the 1.62 billion cases of anemia are because of poor diet and iron deficiency. Currently, the use of iron-enriched yeasts can be used as the most effective and possible way to prevent and treat anemia due to the ability of biotransformation of mineral compounds into the organic form. In this research, for the first time, Saccharomyces (S.) boulardii was used for iron enrichment with the aim that the probiotic properties of yeast provide a potential iron supplement besides improving the bioavailability of iron. Also, due to its higher resistance than other Saccharomyces strains against stresses, it can protect iron against processing temperatures and stomach acidic-enzymatic conditions. So, the effect of three important variables, including concentration of iron, molasses and KH2PO4 on the growth and biotransformation of yeast was investigated by the Box-Behnken design (BBD). The best conditions occurred in 3 g/l KH2PO4, 20 g/l molasses and 12 mg/l FeSO4 with the highest biotransformation 27 mg Fe/g dry cell weight (DCW) and 6 g/l biomass weight. Such yeast can improve fermented products, provide potential supplement, and restore the lost iron of bread, which is a useful iron source, even for vegetarians-vegans and play an important role in manage with anemia. It is recommended that in future researches, attention should be paid to increasing the iron enrichment of yeast through permeabilizing the membrane and overcoming the structural barrier of the cell wall.

Effects of fructooligosaccharides and Saccharomyces boulardii on the compositional structure and metabolism of gut microbiota in students.

Fructooligosaccharides (FOS) are a common prebiotic widely used in functional foods. Meanwhile, Saccharomyces boulardii is a fungal probiotic frequenly used in the clinical treatment of diarrhea. Compared with single use, the combination of prebiotics and probiotics as symbiotics may be more effective in regulating gut microbiota as recently reported in the literature. The present study aimed to investigate the effects of FOS, S. boulardii and their combination on the structure and metabolism of the gut microbiota in healthy primary and secondary school students using an in vitro fermentation model. The results indicated that S. boulardii alone could not effectively regulate the community structure and metabolism of the microbiota. However, both FOS and the combination of FOS and S. boulardii could effectively regulate the microbiota, significantly inhibiting the growth of Escherichia-Shigella and Bacteroides, and controlling the production of the gases including H2S and NH3. In addition, both FOS and the combination could significantly promote the growth of Bifidobacteria and Lactobacillus, lower environmental pH, and enhance several physiological functions related to synthesis and metabolism. Nevertheless, the combination had more unique benefits as it promoted the growth of Lactobacillus, significantly increased CO2 production and enhanced the functional pathways of carbon metabolism and pyruvic acid metabolism. These findings provide guidance for clinical application and a theoretical basis for the development of synbiotic preparations.

Saccharomyces boulardii (CNCM I-745) alleviates collagen-induced arthritis by partially maintaining intestinal mucosal integrity through TLR2/MYD88/NF-κB pathway inhibition.

BACKGROUND: Rheumatoid arthritis, a condition characterized by inflammation, has a substantial influence on both the worldwide economy and public health. Prior studies indicate that probiotics have the potential to enhance the composition of gut microbiota in instances of intestinal dysbiosis resulting from different disorders and contribute to the regulation of inflammation. The objective of this study is to investigate the impact of Saccharomyces boulardii on the gut microbiome in arthritis and its implications on inflammation. METHODS: The study utilized the Collagen Induced Arthritis (CIA) Sprague-Dawley (SD) rat model. After administering Saccharomyces boulardii (150 mg/kg/day) six days a week and Methotrexate (MTX) (0.2 mg/week) treatment for eight weeks, microbial DNA from the feces was sequenced using 16S rRNA. The evaluation of histopathology, bone loss, and cartilage degradation was conducted using histology, immunohistology assays, and micro-computed tomography (µCT) examinations. The enzyme-linked immunosorbent assay (ELISA) was used to analyze proinflammatory cytokines, while the western blot technique was applied to detect protein in the gut and in cell lines. The quantification of gene expression in gut,joint and cell lines was performed using real-time polymerase chain reaction. The cell lines were activated and then treated with the culture supernatant of S. boulardii for an in vitro investigation. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was utilized to assess cell proliferationand viability. Cellular motility was measured in a wound healing experiment, whereas apoptotic proteins were analyzed using Western blotting. RESULTS: S. boulardii has been found to enhance bone and joint integrity, modulate gut microbiota, and mitigate proinflammatory cytokine levels in rats with arthritis. It decreases the permeability of the intestines and promotes the production of gut tight-junction proteins. The administration of S. boulardii inhibits the proliferation of T-helper-17 (Th17) and Type 3 innate lymphoid cells (ILC3). Additionally, it elicits apoptosis in MH7A cell lines and hinders their migratory activity. CONCLUSION: This study provides valuable insights into the therapeutic potential of S. boulardii for treating and preventing arthritis in rats with collagen-induced arthritis by modulating gut microbiota and inflammation.

Randomized controlled trial comparing the impacts of Saccharomyces boulardii and Lactobacillus rhamnosus OF44 on intestinal flora in cerebral palsy rats: insights into inflammation biomarkers and depression-like behaviors.

Background: Cerebral palsy (CP) is a unique neurological disorder which adversely affects motion. Cytokines and gut microbial composition contribute to CP and other diseases, such as reproductive tract inflammation and bone loss. Importantly, Saccharomyces boulardii (S. boulardii) reduces the degree of inflammation and improves overall health status. As our previous study showed that Lactobacillus rhamnosus (L. rhamnosus) OF44, a selected strain of gut bacteria originally used to treat reproductive tract inflammation and bone loss, has effects similar to that of S. boulardii, we decided to use L. rhamnosus OF44 on CP rats. Validation of the effects of L. rhamnosus OF44 on CP adds to its confirmed effects in treating osteoporosis and reproductive tract microbiota disorders, increasing its potential as a probiotic. The purpose of this was to ascertain whether L. rhamnosus OF44 can alleviate the symptoms of CP. Methods: CP rat models were created through left carotid artery ligation. Following this, 100-day old CP rats were exposed to L. rhamnosus OF44, S. boulardii, or normal saline gastric gavage daily for 28 days. Grouping of the rats is determined randomly. Before and after the gavage, behavioral experiments were conducted and the inflammation levels assessed via measurements of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) inflammatory markers. The efficacy of the outcome is measured by performing statistical analysis like the t-test on the data to see its significance. Additionally, variations inside gut microbiome were evaluated via 16S ribosomal RNA sequencing. Results: Before intervention, CP rats failed to exhibit depression-like behavior (P=0.6). L. rhamnosus OF44 treatment significantly reduced the level of IL-6 (P=4.8e-05), S. boulardii treatment significantly reduced the level of TNF-α (P=0.04). In addition, both treatments altered the composition and complexity of the gut microbiome. Conclusions: Our results indicated that L. rhamnosus OF44 has potential in alleviating inflammation and altering the gut microbial composition in CP, and that it has the potential to clinically treat CP. There are some limitations of this study. For example, dietary differences and their effects on gastrointestinal dysfunction are not considered in this study, and only two behavioral experiments were used.

Gut Microbiota Modulation by Selenium and Zinc Enrichment Postbiotic on Dysbiosis Associated with Hypertension.

BACKGROUND: Targeting gut dysbiosis to treat chronic diseases or to alleviate the symptoms is a new direction for medical adjuvant therapies. Recently, postbiotics have received considerable attention as they are non-viable probiotic preparations that confer various health benefits to the host without the safety problems associated with using live microbial cells. OBJECTIVE: The aim of the study is to obtain selenium (Se) and zinc (Zn) enriched Saccharomyces boulardii postbiotic biomass and to analyze its modulation effect because these minerals play an important role in reducing gut dysbiosis linked to cardiovascular (CV) diseases. METHOD: The effect of the S. boulardii and Se/Zn enriched yeast postbiotics on CV microbial fingerprint was studied in vitro using the gastrointestinal system (GIS 1) and analyzed by microbiological, chemical, and qPCR methods. RESULT: There was a 2.2 log CFU/mL increase in the total bacterial load after SeZn postbiotic treatment and in the qPCR counts of Firmicutes phyla for both treatments. Beneficial taxa, Bifidobacterium spp. and Lactobacillus spp., as well as Bacteroides spp. were up to 1.5 log higher after mineral- enriched postbiotic application, while the acetic acid level increased. CONCLUSION: These preliminary studies highlight the therapeutic potential of using Se/Zn enriched yeast postbiotics as adjuvants for clinical treatments of CV diseases.

Coadministration of Lactulose with Probiotics Ameliorates Loperamide-Induced Constipation in Mice.

We evaluated the efficacy of mixtures of lactulose with probiotic strains to ameliorate constipation and to identify suitable probiotic strains. Constipation was induced in Institute of Cancer Research mice (6-week-old, male) by the administering loperamide (5 mg/kg, twice a day) orally for 5 days, whereas the control group was not treated. To evaluate the laxative effects of the lactulose-probiotic and lactulose-magnesium hydroxide mixtures, fecal parameters, the gastrointestinal (GI) transit ratio, and fecal short-chain fatty acid (SCFA) content were analyzed. The administration of lactulose and Bacillus licheniformis or Saccharomyces boulardii significantly improved stool number and water content, which were reduced by loperamide. The GI transit ratio was significantly increased compared with that of the control group. The combined administration of lactulose and probiotics (B. licheniformis or S. boulardii) increased total SCFA content, including that of acetate, more effectively compared with lactulose alone. Similarly, coadministration of lactulose and magnesium hydroxide improved the loperamide-induced changes in fecal parameters and GI transit as well as increased total SCFA content. Overall, the combination of lactulose and probiotics relieves the symptoms of constipation by increasing SCFA content and is more effective compared with lactulose alone.