Article

Review article: Yeast as probiotics - Saccharomyces boulardii

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  • Scientific Center of Monaco
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Abstract

Probiotics are defined as live micro-organisms which confer a health benefit on the host. Although most probiotics are bacteria, one strain of yeast, Saccharomyces boulardii, has been found to be an effective probiotic in double-blind clinical studies. To compare the main properties that differentiates yeast from bacteria and to review the properties of S. boulardii explaining its potential benefits as a probiotic. The PubMed and Medline databases were searched using the keywords 'probiotics', 'yeast', 'antibiotic associated diarrhea', 'Saccharomyces boulardii','bacterial diarrhea' and 'inflammatory bowel disease' in various combinations. Several clinical studies have been conducted with S. boulardii in the treatment and prevention of various forms of diarrhoea. Promising research perspectives have been opened in terms of maintenance treatment of inflammatory bowel diseases. The mechanism of S. boulardii's action has been partially elucidated. Saccharomyces boulardii is a strain of yeast which has been extensively studied for its probiotic effects. The clinical activity of S. boulardii is especially relevant to antibiotic-associated diarrhoea and recurrent Clostridium difficile intestinal infections. Experimental studies clearly demonstrate that S. boulardii has specific probiotic properties, and recent data has opened the door for new therapeutic uses of this yeast as an 'immunobiotic'.

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... The most studied, and perhaps the most promising, probiotics used in adult horses are Saccharomyces cerevisiae and boulardii, two species of non-pathogenic yeasts that are closely related and have the potential to produce proteases able to degrade toxins [136]. In addition, they carry important amounts of mannan oligosaccharide, a constituent of their cell wall that might be used by bacteria as substrate, possibly favoring the growth of beneficial species of bacteria in the gut. ...
... However, in one study S. boulardii was no longer detectable in the feces ten days after cessation of supplementation [140], suggesting that Saccharomyces is likely to survive the acidic pH of the stomach in horses but may not colonize the gastrointestinal tract permanently. Some yeast can grow at a pH of three, and some can tolerate and survive in environments with a pH as low as 1.5 [136]. It is counter-intuitive to supplement bacterial probiotics concomitant with the treatment with antimicrobials; therefore, the use of Saccharomyces spp. ...
... It is counter-intuitive to supplement bacterial probiotics concomitant with the treatment with antimicrobials; therefore, the use of Saccharomyces spp. might be a good strategy in those cases [136]. ...
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Understanding the importance of intestinal microbiota in horses and the factors influencing its composition have been the focus of many studies over the past few years. Factors such as age, diet, antibiotic administration, and geographic location can affect the gut microbiota. The intra- and inter-individual variability of fecal microbiota in horses complicates its interpretation and has hindered the establishment of a clear definition for dysbiosis. Although a definitive causal relationship between gut dysbiosis in horses and diseases has not been clearly identified, recent research suggests that dysbiosis may play a role in the pathogenesis of various conditions, such as colitis and asthma. Prebiotics, probiotics, and fecal microbiota transplantation to modulate the horse’s gastrointestinal tract may eventually be considered a valuable tool for preventing or treating diseases, such as antibiotic-induced colitis. This article aims to summarize the current knowledge on the importance of intestinal microbiota in horses and factors influencing its composition, and also to review the published literature on methods for detecting dysbiosis while discussing the efficacy of gut microbiota manipulation in horses.
... Sb has been believed to encompass pathogen exclusion, enhancement of gut barrier function, immune modulation, and trophic effects. Although most of these efficacies have been validated in animal models or humans through placebo-controlled clinical trials [12], the intrinsic mechanisms behind the efficacies are not entirely understood yet [1,12]. Also, investigations on Sb have predominantly aimed at uncovering potential mechanisms behind its beneficial properties and exploring its applications as a probiotic strain only [4]. ...
... Sb has been believed to encompass pathogen exclusion, enhancement of gut barrier function, immune modulation, and trophic effects. Although most of these efficacies have been validated in animal models or humans through placebo-controlled clinical trials [12], the intrinsic mechanisms behind the efficacies are not entirely understood yet [1,12]. Also, investigations on Sb have predominantly aimed at uncovering potential mechanisms behind its beneficial properties and exploring its applications as a probiotic strain only [4]. ...
... The adhesive interaction between the pathogenic bacteria and the Saccharomyces yeast surface can contribute to the therapeutic efficacy of Sb against enteric diseases, as the rivalry between yeast cell wall mannan and oligomannoside chains on enterocytes reduces the colonization and infection chances of the pathogenic bacteria [32,55,56]. Because Saccharomyces yeasts stay in the host gut transiently, yeast cells pass through the host gut, capturing pathogenic bacteria and ultimately diminishing the intestinal population of the pathogens [12,50]. Nevertheless, the in vivo substantiation of the parabiotic protective efficacy of Sb predicated on adhesive interactions with pathogens remains unestablished. ...
Article
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Saccharomyces cerevisiae var. boulardii (Sb) is currently receiving significant attention as a synthetic probiotic platform due to its ease of manipulation and inherent effectiveness in promoting digestive health. A comprehensive exploration of Sb and other S. cerevisiae strains (Sc) would shed light on the refinement and expansion of their therapeutic applications. This review aims to provide a thorough overview of Saccharomyces yeasts from their native health benefits to recent breakthroughs in the engineering of Saccharomyces yeasts as synthetic therapeutic platforms. Molecular typing and phenotypic assessments have uncovered notable distinctions, including the superior thermotolerance and acid tolerance exhibited by Sb, which are crucial attributes for probiotic functions. Moreover, parabiotic and prebiotic functionalities originating from yeast cell wall oligosaccharides have emerged as pivotal factors influencing the health benefits associated with Sb and Sc. Consequently, it has become imperative to select an appropriate yeast strain based on a comprehensive understanding of its actual action in the gastrointestinal tract and the origins of the targeted advantages. Overall, this review underscores the significance of unbiased and detailed comparative studies for the judicious selection of strains.
... Cell size [15] 10 µm 1 µm ...
... Cell wall [15] Chitin, mannose (PPM, PLM), glucan Peptidoglycan, LPS (Gram-negative), LTA (Gram-positive) ...
... Optimal growth conditions-pH [15] 4.5-6.5 6.5-7.5 ...
Article
Probiotics, both bacterial and yeast, have long been associated with a beneficial health history and human well-being. Among yeasts, Saccharomyces is a genus that is efficacious in rendering better human health, with Saccharomyces boulardii (S. boulardii) CNCM I-745 being classified as a probiotic agent. The present review highlights the unique properties of S. boulardii and its role in the prevention of antibiotic-associated diarrhea (AAD) and pediatric acute gastroenteritis (PAGE) in comparison to bacterial probiotics. Its unique properties, such as viability over a wide pH range, inability to acquire antibiotic resistance genes, and property to achieve a steady state rapidly, have given S. boulardii an edge over bacterial probiotics. In AAD patients, prophylactic use of S. boulardii has shown a significantly lower risk of AAD (in comparison to controls) and restored the diversity of gut microbiota. Among Indian children with PAGE, S. boulardii CNCM I-745 was found superior to Lactobacillus rhamnosus GG and four strains of Bacillus clausii in shortening the duration of diarrhea and reducing the length of hospital stay. S. boulardii CNCM I-745 being considered a safe probiotic for use in children and adults also finds recommendations in several international guidelines for the management of acute diarrhea. The current review discusses evidence for the proven efficacy and safety of S. boulardii CNCM I-745 as a probiotic for preventing gastrointestinal disorders.
... Acute diarrhoeal disease (ADD) is defined as the expulsion of 3 or more liquid stools, with or without blood, within 24 h, that take the shape of the container in which they are placed. A diarrhoeal episode is one that meets the above criteria and ends when the last day of diarrhoea is followed by at least 48 h of normal stools [3]. Acute diarrhoea lasts less than 14 days, diarrhoea lasting more than 14 days is called persistent diarrhoea, and diarrhoea lasting more than 1 month is called chronic diarrhoea. ...
... Probiotics can be bacterial or yeast microbes. Yeast probiotics, such as Saccharomyces boulardii (Sb), are different from bacterial probiotics [3].Sb has several different mechanisms of action that can be classified into 3 main areas: luminal action, trophic action, and mucosal anti-inflammatory signalling effects. Sb has several benefits such as interference with pathogenic toxins and pathogen adhesion, preservation of cell physiology, interactions with the normal microbiota, and restoration of short-chain fatty acid level. ...
... For example, Sb induces high levels of IgA and interleukin 10 in the bowel, and these participate in the immunomodulatory response to infection. Specific beneficial effects have been reported in the treatment of children with ADD, prevention of C. difficile infections, and prevention of diarrhoea associated with the use of antibiotics, including anti-toxin and anti-inflammatory effects, trophic effects on enterocytes, stimulation of the immune response, increase in disaccharidase levels, elimination of toxins and pathogens, and interference with the bacterial signalling pathways [3]. ...
Article
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Background Probiotics are effective for treating acute infectious diarrhoea caused by bacteria, but there are inconsistent results for the effectiveness of probiotics for diarrhoea caused by viruses. In this article we want to determine whether Sb supplementation has an effect on acute inflammatory viral diarrhoea diagnosed with the multiplex panel PCR test. The aim of this study was to evaluate the efficacy of Saccharomyces boulardii (Sb) as a treatment in patients diagnosed with viral acute diarrhoea. Methods From February 2021 to December 2021, 46 patients with a confirmed diagnosis of viral acute diarrhoea diagnosed with the polymerase chain reaction multiplex assay were enrolled in a double-blind, randomized placebo-controlled trial. Patients received paracetamol 500 mg as a standard analgesic and 200 mg of Trimebutine as an antispasmodic treatment plus 600 mg of Sb (n = 23, 1 × 109/100 mL Colony forming unit) or a placebo (n = 23) orally once daily for eight days. The improvement in and severity of symptoms were measured using a symptom diary, the Patient Global Impression and the Patient Global Impression of Change scales (days 4 and 8), both answered and recorded by the patient. Results Of the 46 patients who completed treatment, 24 (52%) were men and 22 (48%) were women. The average age was 35.6 ± 12.28 years (range 18 to 61 years). The average duration of the evolution of illness at the time of diagnosis was 0.85 ± 0.73 days (maximum 2 days). On day 4 after the diagnosis, 20% reported pain and 2% reported fever, but on day 8, no patient reported pain or fever. On day 4, 70% of patients in the Sb group and 26% in the placebo group reported improvement (P = 0.03), based on the Patients’ Global Impression of Change scale, which assesses patient’s rating of overall improvement. These findings suggest that 3 to 4 days of treatment with Sb helped to improve symptoms of diarrhoea caused by a virus. Conclusion Treatment with Sb on acute inflammatory diarrhoea of viral aetiology shows no changes regarding the severity of the symptoms; nevertheless, it seems to impact improvement positively. Trial registration 22CEI00320171130 dated on 16/12/2020, NCT05226052 dated on 07/02/2022.
... 6 The yeast cells of Sb, if compared to bacterial probiotics, have a few advantages, like antibiotic resilience due to its fungal nature, resistance to stomach and bile acids, survival at human body temperature, and inhibition of pathogenic growth. 8 As seen in Table 1, Sb is more robust to temperature and acidic stimuli but less tolerant to bile salts. Sb differs from bacterial probiotics by its ability to improve the microbiota composition in the gut and promote humoral and innate immunity in healthy subjects. ...
... 6 However, a number of effective mechanisms have been uncovered which directly influence both the host and the response of pathogenic microorganisms by modulating the local and systemic immune responses, regulating intestinal microbial homeostasis, interfering with pathogen colonization, inducing the enzymatic activity that favors absorption and nutrition and stabilizes the GI barrier. 8,10,12,13 The following are the key mechanisms by which yeast probiotics (Sb) function: ...
... 64 These benefits include natural immunity to antibacterial antibiotics, the capability of growth temperature, the ability to sustain, sensitivity to acid and bile salts, cellular hydrophobicity as well as the capacity for auto-aggregation, the capacity for assimilation of cholesterol, and greater cell size in comparison to bacterial probiotics. 3,8,[17][18][19]21 The role of yeast probiotics in GI diseases, primarily IBS, AAD, and HpSA infection, is addressed in the current review. IBS is characterized by frequent, chronic stomach aches or uneasiness and irregular bowel movements. ...
Article
The human gut is home to a variety of microbes, including bacteria, viruses, fungi, eukaryotes, and archaea, which together form a complex structure. In general, the microbiota that colonizes the gastrointestinal (GI) tract plays a significant role in maintaining human health and has been implicated in the pathogenesis of a number of GI illnesses. The structural integrity and metabolic processes of the alimentary canal are physiologically influenced by the dynamic interactions between the gut and bacteria. GI dysbiosis is a result of an imbalance brought on by a decline in microbial diversity, the loss of helpful bacteria, and an increase in pathobionts. It is crucial to restoring the gut microbiota. In order to regain the eubiotic state of the microbial flora, varied methods are being researched and implemented. The use of probiotics is one strategy for re-establishing healthy gut flora. Probiotics are "living microorganisms" that improve the health of the host when provided in adequate quantities. There are two types of probiotics-bacteria and yeast-based. The review will look at and summarize the information for yeast-based Saccharomyces probiotics regarding their effectiveness and safety in treating a variety of patient diseases, particularly irritable bowel syndrome (IBS), antibiotic-associated diarrhea, and Heliobacter pylori (HpSA) infection. The only commercially accessible yeast probiotic, the Saccharomyces strain, which consists of Saccharomyces cerevisae (S. cerevisiae) and Saccharomyces boulardii (Sb), provides a number of benefits over bacterial probiotics. The significance of Sb as a potent biotherapeutic medication that may be utilized to prevent or treat a variety of GI disorders has been substantiated by several experimental studies and clinical trials.
... Human health and the gut microbiome are intimately intertwined [8]. The gut microbiome's (GM) microbes coexists with the host in harmony and form an extremely complex ecosystem [9]. The GM makes a crucial contribution in host metabolism, which is heavily involved in food digestion, energy supplementation and immune system development [10]. ...
... Probiotics have been around for as long as there have been fermented food consumed by humans. Most probiotic micro-organisms are bacteria [9]. ...
... Many countries utilize this yeast as a preventive and therapeutic treatment for diarrhea and other gastrointestinal (GI) conditions caused by the use of antimicrobial drugs. S. boulardii has many characteristics that make it a promising probiotic agent, including the ability to survive along the GI tract, a preferred temperature range of 37°C and the ability to suppress the growth of many microbial pathogens, both in vitro and in vivo [9]. ...
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Non-nutritive sweeteners (NNS) are a well-known substitute for table sugar with great implications in the management of various pathologies, mainly in Diabetes or Obesity. Previous studies have successfully shown that these substances are safe for human consumption, but one concern that remains is that of the impact on gut microbiota, mainly due to the complexity and diversity of the microbiome in humans. Keeping in mind that the gut microbiota contains numerous of Lactobacillus and Saccharomyces species, we simulated the microbiome by obtaining isolated microbial cultures of Saccharomyces boulardii and Lactobacillus reuteri, which we obtained two over the counter (OTC) probiotic supplements. We evaluated the bacteriostatic effect of three sweeteners (Sucralose, Saccharin, Stevia), using the successive dilution method and disc-diffusometry on solid medium. What we sought to determine was a minimum inhibitory concentration (MIC) of each non-nutritive sweetener.
... Although studies evaluating the probiotic potential of yeast have increased [19,26], only one commercial species is available in the world for human consumption, Saccharomyces cerevisiae var. boulardii [27,28]. However, recent studies have given notoriety to the strain Kluyveromyces marxianus fragilis B0399, due to its beneficial properties toward some disorders [29][30][31]. ...
... In addition, it has been proven that some yeast species benefit the human body by tolerating conditions imposed on the gastrointestinal tract (GIT) and resistance to antibiotics [32]. Furthermore, yeast cannot disseminate pathogen resistance genes and are rapidly cleared from the human body after cessation of probiotic consumption [28,32]. This work aimed to isolate and identify endogenous yeasts from the Serro region (pingo and rala) of the QMA. ...
... However, it has been proven that some yeast species benefit the human organism by tolerating conditions imposed on the gastrointestinal tract (GIT) and antibiotic resistance [32]. Furthermore, yeasts cannot disseminate resistance genes to pathogens and are quickly eliminated from the human body after the cessation of probiotic consumption [28,32]. This work aimed to isolate and identify yeast from the Serro region's endogenous ferment (pingo and rala) of QMA. ...
Article
Artisanal Minas cheese (QMA) is traditionally elaborate using raw milk and endogenous ferment (pingo - whey or rala - grated ripened cheese). In the present study, 91 yeast strains were isolated and identified from pingo and rala. Eight yeast species were identified by the MALDI-TOF mass spectrometry and confirmed by sequencing of the ITS region. The yeasts' protease and lipase activities were evaluated in addition to probiotic properties such as tolerance to low pH and bile salts, hydrophobicity, autoaggregation, co-aggregation with pathogens, and antimicrobial susceptibility. The rala ferment showed a greater variety of species. Yarrowia lipolytica was the dominant specie (52.7% of isolates), followed by the Kluyveromyces lactis and Kodamaea ohmeri (9.9 and 6.6%, respectively). From the total yeasts evaluated, 74 strains showed positive enzymatic activity: 52 strains showed lipolytic (51 Y. lipolytica and one Trichosporon japonicum) and 44 proteolytic activities (18 Y. lipolytica, 13 K. ohmeri, 11 K. lactis, and 2 Wickerhamiella sp.). All evaluated isolates demonstrated tolerance to pH 2.0, and 69 isolates supported the presence of bile salts. From them, 12 isolates showed the capacity of autoaggregation (> 30%) and hydrophobicity (> 90.0%) and were then selected for co-aggregation and antibiotic resistance assays. All selected isolates showed co-aggregation with Salmonella Enteritidis, Escherichia coli, and Listeria monocytogenes greater than 30%. None of the yeast showed sensibility to the evaluated antibiotics and antagonistic activity against the evaluated pathogens. The results demonstrated that pingo and rala have different yeast composition with different enzymatic activity, which may affect the characteristics of the cheese. Furthermore, some yeast strains: Y. lipolytica (9 strains isolated from rala) and K. ohmeri (3 strains isolated from pingo) demonstrated attractive probiotic potential.
... Further taxonomic, metabolic, and genetic properties analysis revealed that the two strains have different genetic composition and enzyme profiles (1,3). Moreover, S. boulardii has a unique and specific microsatellite allele characteristics that distinguishes it from other strains of S. cerevisiae (4). Characterization of S. boulardii as a separate species was additionally supported by the lack of galactose utilization and sporulation as compared to S. cerevisiae (5). ...
... For the determination of probiotic properties, several major selection criteria were carried out, such as tolerance against a range of temperatures, bile salt, simulated gastrointestinal digestion, hydrophobicity of cell, autoaggregation and salinity (NaCl), as well as resistance to low pH (4). According to the suggestion of FAO/WHO, it is mandatory to perform a preliminary in vitro assessment before assessing the probiotic properties of microorganisms (14,25). ...
... In the present study, only one isolate was found to exhibit a strong affinity with high temperatures, and was able to (2,4). As a result, this isolate initially presumes as S. boulardii and was chosen for further study. ...
... 13 Yeasts are good candidates as probiotics because yeasts entering the gastrointestinal tract are resistant to local stresses such as the presence of enzymes, bile salts, organic acids and considerable variations of pH and temperature, including high acidity. 14 Yeasts are single-cell micro-organisms belonging to the fungus family and can quickly multiply by means of cell division. Yeast extract is obtained from natural yeast through autolyzing baker's yeast or brewers' yeast, 15 degrading the proteins and nucleic acids from the cell wall, making valuable components from the yeast cells available to the human body. ...
... In addition, a whole range of secondary metabolites, including vitamins, polyols or antioxidants, may bring specific health benefits. 14 TA B L E 2 Effect of yeast extract on RPMCs after TTX. metabolism and inflammatory responses, as there are SCFA receptors and target molecules expressed in metabolic and immune tissues. ...
Article
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Fermented foods play a significant role in the human diet for their natural, highly nutritious and healthy attributes. Our aim was to study the effect of yeast extract, a fermented substance extracted from natural yeast, on colonic motility to better understand its potential therapeutic role. A yeast extract was given to rats by gavage for 3 days, and myogenic and neurogenic components of colonic motility were studied using spatiotemporal maps made from video recordings of the whole colon ex vivo. A control group received saline gavages. The yeast extract caused excitation of the musculature by increasing the propagation length and duration of long‐distance contractions, the major propulsive activity of the rat colon. The yeast extract also evoked rhythmic propulsive motor complexes (RPMCs) which were antegrade in the proximal and mid‐colon and retrograde in the distal colon. RPMC activity was evoked by distention‐induced neural activity, but it was myogenic in nature since we showed it to be generated by bethanechol in the presence of tetrodotoxin. In conclusion, ingestion of yeast extract stimulates rat colon motility by exciting neurogenic and myogenic control mechanisms.
... Az élesztőgombák egyszerű eukarióták, kevesebb mint 0,1%-ban vannak jelen a humán mikrobiomban, míg a probiotikus baktériumok a mikrobiom 99%-át adják. 13 Az élesztőgombák mérete tízszeres, alacsonyabb pH-n is képesek anyagcserét folytatni (pl. már a vékonybél proximalis részén is) és nem kolonizálják a bélrendszert. ...
... A S. boulardii további metabolitok termelése által a nyálkahártyán létrejövő oxidatív stresszt is képes csökkenteni. 13 Egészséges egyénekben a S. boulardii nincs hatással a mikrobiom összetételére, de előnyös hatással bír az egyensúly felborulása esetén, főképp antibiotikum asszociált intestinalis dysbiosis esetén. A S. boulardii elősegíti a bélmikrobiom diverzitásának javulását antibiotikumkezelést követően. ...
Article
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Az antibiotikumok széles körű alkalmazása a bélmikrobiom egyensúlyának felborulásához vezethet, amely klinikailag leggyakrabban hasmenés formájában nyilvánul meg. A szerző részletesen tárgyalja az antibiotikumok által kiváltott gyomor-bél rendszeri mellékhatásokat, hangsúlyozva a bélflóra diverzitásának csökkenését, a potenciálisan káros törzsek és a rezisztenciagének elterjedését, valamint a metabolikus károsodásokat. Az intestinalis barrier, amely a bélnyálkahártya fizikai, szekretoros és immunológiai gátját jelenti, szintén az antibiotikumok célpontja. A szerző áttekinti az intestinalis dysbiosis enyhítése céljából alkalmazott probiotikus gombák nyújtotta terápiás lehetőségeket is.
... Currently published studies do not provide conclusive evidence of their benefits and yield contradictory results. Yeast probiotics have various advantages over probiotics containing mainly bacteria, such as their resistance to acidic environments and antimicrobials, which are often used in ill patients with concomitant dysbiosis [129]. Saccharomyces cerevisiae or boulardii are two nearly identical strains of nonpathogenic yeasts that can release proteases to degrade C. difficile toxins A and B [129]. ...
... Yeast probiotics have various advantages over probiotics containing mainly bacteria, such as their resistance to acidic environments and antimicrobials, which are often used in ill patients with concomitant dysbiosis [129]. Saccharomyces cerevisiae or boulardii are two nearly identical strains of nonpathogenic yeasts that can release proteases to degrade C. difficile toxins A and B [129]. The effects of Saccharomyces in horses with asthma have yet to be examined, but in mice models of asthma sensitized to OVA, significant reductions in AHR and airway inflammation were observed in the mice treated with S. cerevisiae [130,131]. ...
Article
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Both microbe–microbe and host–microbe interactions can have effects beyond the local environment and influence immunological responses in remote organs such as the lungs. The crosstalk between the gut and the lungs, which is supported by complex connections and intricate pathways, is defined as the gut–lung axis. This review aimed to report on the potential role of the gut–lung gut–lung axis in the development and persistence of equine asthma. We summarized significant determinants in the development of asthma in horses and humans. The article discusses the gut–lung axis and proposes an integrative view of the relationship between gut microbiota and asthma. It also explores therapies for modulating the gut microbiota in horses with asthma. Improving our understanding of the horse gut–lung axis could lead to the development of techniques such as fecal microbiota transplants, probiotics, or prebiotics to manipulate the gut microbiota specifically for improving the management of asthma in horses.
... S. boulardii is a non-pathogenic yeast that is able to resist stomach acid, bile, and proteolytic enzymes. Compared to other bacterial probiotics, its major distinction is its inherent resistance to antibiotics, making it suitable for use in conjunction with antibiotics [36,37]. It is unclear exactly how S. boulardii eliminates H. pylori, but there are a few possible explanations. ...
... One is that it produces substances, such as short chain fatty acids, that inhibit H. pylori growth [38]. Additionally, S. boulardii has a larger surface area than other probiotics, so it can better adhere to the gastric mucosa, preventing H. pylori colonization and adhesion [37]. The neuraminidase present in S. boulardii can also remove H. pylori adhesin ligands and stop the bacteria from attaching to the duodenal mucosa [39]. ...
Article
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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.
... S. boulardii has caught a lot of attention as an AMT chassis for its unique characteristics 27,28 and inherent properties. 26,51 Due to its eukaryotic nature, S. boulardii offers advantages in terms of post-translational modifications and proper folding of complex therapeutic peptides, making it a promising candidate for the production and secretion of bioactive molecules. Furthermore, compared to bacterial systems, yeast species typically exhibit lower endotoxin contamination levels, and there is a reduced risk of horizontal gene transfer and potential spread of antibiotic resistance genes, mitigating concerns related to these factors. ...
... Furthermore, compared to bacterial systems, yeast species typically exhibit lower endotoxin contamination levels, and there is a reduced risk of horizontal gene transfer and potential spread of antibiotic resistance genes, mitigating concerns related to these factors. 51 These inherent properties, coupled with S. boulardii's established safety profile (GRAS) and the demonstrated ability to ameliorate certain disease phenotypes observed in db/db mice, 26 further highlight its potential as a safe and promising host for the oral delivery of therapeutic peptides. However, there is limited evidence of S. boulardii as an AMT chassis, particularly in the field of metabolic disorders. ...
Article
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Advanced microbiome therapeutics (AMTs) holds promise in utilizing engineered microbes such as bacteria or yeasts for innovative therapeutic applications, including the in situ delivery of therapeutic peptides. Glucagon-like peptide-1 receptor agonists, such as Exendin-4, have emerged as potential treatments for type 2 diabetes and obesity. However, current administration methods face challenges with patient adherence and low oral bioavailability. To address these limitations, researchers are exploring improved oral delivery methods for Exendin-4, including utilizing AMTs. This study engineered the probiotic yeast Saccharomyces boulardii to produce Exendin-4 (Sb-Exe4) in the gastrointestinal tract of male C57BL/6 mice to combat diet-induced obesity. The biological efficiency of Exendin-4 secreted by S. boulardii was analyzed ex vivo on isolated pancreatic islets, demonstrating induced insulin secretion. The in vivo characterization of Sb-Exe4 revealed that when combined with cold exposure (8 °C), the Sb-Exe4 yeast strain successfully suppressed appetite by 25% and promoted a 4-fold higher weight loss. This proof of concept highlights the potential of AMTs to genetically modify S. boulardii for delivering active therapeutic peptides in a precise and targeted manner. Although challenges in efficacy and regulatory approval persist, AMTs may provide a transformative platform for personalized medicine. Further research in AMTs, particularly focusing on probiotic yeasts such as S. boulardii, holds great potential for novel therapeutic possibilities and enhancing treatment outcomes in diverse metabolic disorders.
... Probiotics release antibacterial substances or metabolites, such as lactic acid, preventing the growth of pathogens, activating the host immune response, and improving epithelial barrier function [7][8][9]. Lactic acid bacteria are the main probiotic group; Lactobacilli, like Lactobacillus acidophilus and Lactobacillus rhamnosus, and Bifidobacteria are the most commonly used [10,11]. Moreover, a few non-lactic microorganisms have been used, as in the case of the yeast Saccharomyces cerevisiae var. ...
... boulardii, which has been demonstrated to be an effective probiotic. This yeast has been shown to be a preventive and therapeutic agent for diarrhea and other gastrointestinal disorders produced as a consequence of antimicrobial agent administration [10]. Furthermore, other healthy properties, including antibacterial, antiviral, antioxidant, anticarcinogenic, anti-inflammatory, immunomodulatory, etc., have been clinically demonstrated [12]. ...
Article
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The development of new non-dairy probiotic foods is interesting, given lactose intolerance, milk allergies, and the growing trend of vegetarianism. In this paper, beer has been used as a probiotic delivery matrix, using Saccharomyces boulardii as an alternative to conventional brewer’s yeast. The strain was able to grow in worts prepared with hops containing different alpha-acid concentrations, attaining in all cases a final cell concentration above 1·108 cells mL−1. Some differences were found in the physicochemical parameters of beers brewed with S. boulardii compared to those brewed with a standard brewer’s yeast. Probiotic beers turned out to be less cloudy, which could help with a possible filtering step; less alcoholic in some cases; a healthier alternative; and with a slightly lower pH, interesting for the reduction of spoilage risk. Thirty volatile compounds were determined in the samples, and, in general, the beers brewed with the probiotic yeast presented significantly higher concentrations for the majority of the studied volatile compounds. In addition, multivariate statistical analysis was successfully performed to differentiate the beers obtained in terms of their volatile composition. Probiotic and standard beers were also subjected to sensory analysis, and they presented similar results in their overall impression.
... More than 50 clinical trials (more than 8000 subjects involved in total) have been conducted to date regarding the efficacy of probiotic yeasts. The results point to a major advantage over bacterial probiotics in the prevention and treatment of many gastrointestinal conditions [21]. Cell wall components in yeasts, such as β-glucans, act as antigens recognized by receptors in the host's immune cells and can therefore exert immunomodulating effects. ...
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Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). The current solutions for its management, such as oral rehydration salts (ORS), inhibitors of gut motility, antibiotics, and living probiotics, only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. The potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signalling assays, the gut barrier formation assay, and the rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.
... S. boulardii has the ability to directly inhibit H. pylori through the production of lactic acid, short-chain fatty acids, bacteritin, hydrogen peroxide, neuraminidase, and other substances (28). Furthermore, compared to other probiotic bacterial strains, S. boulardii has a much larger volume, resulting in a greater surface area and improved ability to adhere to pathogenic bacteria, thus impacting the colonization of H. pylori in the gastric mucosa (32). S. boulardii has neuraminidase activity that is specific to alpha (2-3)-linked sialic acid, and it acts by attaching itself to the adhesin of H. pylori, thereby preventing the adhesion of H. pylori in the duodenum (33). ...
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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.
... The seven core genera of microbial organisms most often used in probiotic products are Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus [11]. Yeast probiotics differ from bacterial probiotics in size, cell wall composition, antibiotic resistance and metabolic properties [12,13]. Compared with bacterial probiotics, yeast cells are naturally resistant to antibiotics, as they are fungi, and there is no observed DNA exchange pertaining to antimicrobial resistance genes [14]. ...
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Multiple clinical studies have described the benefits of probiotic Saccharomyces boulardii (S. boulardii) CNCM I-745 against diarrhoea, but the real-world evidence supporting its use is lacking. To evaluate effectiveness of the S. boulardii CNCM I-745 group in a real-world setting. This was an electronic medical record (EMR)-based, retrospective, multicentre, comparative study in Indian adult patients presenting with diarrhoea managed between January 2020 and January 2022. Data of patients at the baseline visit, with a follow-up visit within 15 days, and who were administered S. boulardii CNCM I-745 (for the test group) or any other treatment modality excluding probiotics (for the control group) were considered. Effectiveness was evaluated on the basis of number of patients who did not complain of diarrhoea at follow-up. Of 30,385 adult patients with diarrhoea, 270 patients prescribed S. boulardii CNCM I-745 were included, while the control group comprised 1457 patients. The baseline median age of the test group was 47 years (range 19–86 years), while it was 44 years (range 19–100 years) for the control group. The majority of patients in both study groups were females (56.7% in the test and 51.5% in the control group). Median duration between visits was 5 days (range 1–15 days) in both study groups. In all, 77.8% patients (95% CI 72.34–82.59) in the test group did not complain of diarrhoea at follow-up, while the proportion was 15.8% (95% CI 13.95–17.76) in the control group (p < 0.05). Odds ratio (OR) for absence of diarrhoea in the S. boulardii CNCM I-745 group versus the control group was 18.7 (95% CI 13.6–25.7, p < 0.05). For subgroups on concomitant antibiotics, a significant advantage was noted again for the test versus the control group (76.8% versus 18.4%; p < 0.05; OR: 14.7 with 95% CI 8.8–24.4; p < 0.05). The effect of S. boulardii CNCM I-745 probiotic in controlling diarrhoea was better than anti-diarrhoeal and/or oral rehydration therapy in real-world clinical practice. The effect was similar even with concomitant antibiotic usage.
... certain yeast strains (Saccharomyces cerevisiae var. boulardii) or Escherichia coli strains (E. coli Nissle, 1917) are applied in prophylaxis and therapy since several decades (Czerucka et al. 2007;Ukena et al. 2007). Fungal probiotics is one of the developing fields today (Shruthi et al. 2022), and among them, yeasts represent a huge and diversified group that attracting and expanding the attention of researchers and industries. ...
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Probiotic microorganisms are used to improve the health and wellness of people and the research on this topic is of current relevance and interest. Fifty-five yeasts, coming from honeybee’s ecosystem and belonging to Candida, Debaryomyces, Hanseniaspora, Lachancea, Metschnikowia, Meyerozyma, Starmerella and Zygosacchromyces genera and related different species, were evaluated for the probiotic traits. The resistance to gastrointestinal conditions, auto-aggregation, cell surface hydrophobicity or biofilm formation abilities as well as antimicrobial activity against common human pathogenic bacteria were evaluated. The safety analysis of strains was also carried out to exclude any possible negative effect on the consumer’s health. The influence of proteinase treatment of living yeasts and their adhesion to Caco-2 cells were also evaluated. The greatest selection occurred in the first step of survival at the acidic pH and in the presence of bile salts, where more than 50% of the strains were unable to survive. Equally discriminating was the protease test which allowed the survival of only 27 strains belonging to the species Hanseniaspora guilliermondii, Hanseniaspora uvarum, Metschnikowia pulcherrima, Metschnikowia ziziphicola, Meyerozyma caribbica, Meyerozyma guilliermondii, Pichia kluyveri, Pichia kudriavzevii and Pichia terricola. An integrated analysis of the results obtained allowed the detection of seven yeast strains with probiotic aptitudes, all belonging to the Meyerozyma genus, of which three belonging to M. guillermondii and four belonging to M. caribbica species.
... In our study, we evaluated the in vitro and in vivo safety of our isolates. All the strains were non-hemolytic and sensitive to the clinical antimycotic and antibiotics agents tested, in agreement with other findings regarding the factors that make bacteria and yeasts good probiotic candidates [68], since they should not carry transmissible resistance genes. Indeed, an important requirement for probiotic strains is that they should be, at the same time, resistant to antimicrobials in order to be protected during therapy or preventive activity, but it is also necessary to avoid resistant strains, which can limit effectiveness for human use [69,70]. ...
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Probiotics are known for their health-promoting resources and are considered as beneficial microorganisms. The current study focuses on the isolation, and on a complete in vitro and in vivo characterization, of yeast and lactic acid bacteria acquired from traditional homemade kefir in order to assess their potentiality as probiotic candidates. In particular, the isolates Pichia kudriavzevii Y1, Lactococcus lactis subsp. hordniae LAB1 and Lactococcus lactis subsp. lactis LAB2 were subjected to in vitro characterization to evaluate their suitability as probiotics. Resistance to acid and bile salts, auto-aggregation, co-aggregation, hydrophobicity, and biofilm production capability were examined, as well as their antioxidant activity. A safety assessment was also conducted to confirm the non-pathogenic nature of the isolates, with hemolysis assay and antibiotic resistance assessment. Moreover, mortality in the invertebrate model Galleria mellonella was evaluated. Current findings showed that P. kudriavzevii exhibited estimable probiotic properties, placing them as promising candidates for functional foods. Both lactic acid bacteria isolated in this work could be classified as potential probiotics with advantageous traits, including antimicrobial activity against enteric pathogens and good adhesion ability on intestinal cells. This study revealed that homemade kefir could be a beneficial origin of different probiotic microorganisms that may enhance health and wellness.
... Although naturally found in mucous membranes such as the oral cavity, skin, urinary and genital organs, and intestines, probiotics are commonly seen in dietary supplements and fermented products (e.g., milk products, beer, meat, and kimchi). Administration of adequate probiotics may confer health benefits to the human host regarding treating and preventing certain pathological conditions [24][25][26][27]. Various mechanisms of action of probiotics concerning the beneficial effects on human health, including bone, have been proposed based on in vitro and in vivo studies. ...
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Probiotics have been found to have beneficial effects on bone metabolism. In this randomized, double-blind, placebo-controlled trial, the effects of multispecies probiotic supplementation on bone turnover markers were evaluated after 12 weeks. Forty postmenopausal women with osteopenia were included and randomly divided into two groups. The intervention group received multispecies probiotics, while the control group received identical placebo sachets daily. The baseline characteristics of both groups were similar. Still, the median serum bone resorption marker C-terminal telopeptide of type I collagen (CTX) was slightly higher in the multispecies probiotic group than in the placebo group (0.35 (0.12, 0.53) vs. 0.16 (0.06, 0.75); p-value = 0.004). After 12 weeks, the mean difference in serum CTX at baseline versus 12 weeks was significantly different between the multispecies probiotic and placebo groups (−0.06 (−0.29, 0.05) vs. 0.04 (−0.45, 0.67); p-value < 0.001). The multispecies probiotic group showed a significant decrease in serum CTX at 12 weeks compared with baseline (p-value 0.026). However, the placebo group showed no significant change in serum CTX (p-value 0.18). In conclusion, multispecies probiotics may have a preventive effect on bone through their antiresorptive effect in osteopenic postmenopausal women.
... The probiotic yeast S. boulardii is recognized for its resilience to low pH environments [14]. Notably, it has demonstrated the ability to remain viable even after exposure to simulated gastric juice, which contains pepsin and hydrochloric acid, thus enabling it to survive in stomach-like conditions [21]. Similarly, E. faecium exhibits resistance to low pH and is unaffected by bile salts [13,22], unlike most bacteria, which are unable to survive under such conditions. ...
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Background Commercial airline pilots (APs) are prone to upper gastrointestinal symptoms, such as epigastric pain and bloating. These issues are often linked to occupational risk factors like irregular diet, sleep disruption, and circadian rhythm disturbance. The use of probiotics to enhance intestinal health is well established, but their efficacy in treating upper gastrointestinal diseases is still debated. This is primarily due to the stomach’s small resident microbiota and its low pH, which is inhospitable to most microbes. However, emerging research suggests that specific probiotic strains, such as Enterococcus faecium, can withstand acidic environments. Moreover, certain yeast species, including Saccharomyces boulardii, can survive at a low pH. Consequently, we conducted a preliminary, three-arm, randomized, open-label, dose-finding, four-week study to compare the effects of watchful waiting (WW) with the administration of an oral probiotic supplement containing S. boulardii and E. faecium in APs diagnosed with Helicobacter pylori-negative chronic non-atrophic gastritis (CNG). Methods The study included 39 APs with CNG who were randomized into three groups with a 1:1:1 ratio. The low-dose group (n = 13) received one capsule of the probiotic supplement twice daily, before meals, for four weeks. The high-dose group (n = 13) was administered two capsules of the supplement on the same schedule. The third group (n = 13) underwent WW and served as the control arm. Blinding was maintained for the examining physicians and laboratory staff, but not for the patients. All participants self-rated their experiences of gastric pain and bloating at the beginning and conclusion of the four-week treatment period. Additionally, serum levels of pepsinogen I (PGI) and pepsinogen II (PGII) were measured at these time points. Results Supplementation with probiotics significantly outperformed WW in reducing subjective gastric pain and bloating. This effect was consistent across both tested dosages, with no significant differences observed. However, only high-dose probiotics led to a statistically significant decrease in PGII levels and an increase in the PGI/PGII ratio after the four-week study period, a result not observed with low-dose probiotics. Conclusions Oral administration of S. boulardii and E. faecium demonstrated potential efficacy in reducing gastric pain and bloating symptoms in APs with CNG, as evidenced by statistically significant symptom improvement compared to the control group that did not receive the probiotic supplementation. Notably, high-dose probiotics resulted in a significant increase in the PGI/PGII ratio, indicating potential long-term cytoprotective effects on the gastric mucosa.
... As for piperacilline ( PI), cefotaxime-clavulanic acid( CEC), and tetracycline (TE) antibiotics, the resistance percentage lowered after probiotic treatment, the reason returns, and as studies have suggested, probiotic bacteria and yeast can act as reservoirs for antibiotic resistance genes [20,21]. Inappropriate antibiotic use promotes antimicrobial resistance, leading to increased treatment costs and a prolonged hospital stay. ...
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ackground: Misdiagnosis of the pathogen leads to serious consequences. Diarrhea is a worldwide health problem that kills 1.3 million people each year. Diarrhea can be induced by a variety of causes. However, infectious agents like bacteria are among the leading causes. Several resistant bacterial strains are emerging that tend to spread globally; hence, resistance of bacteria to antibiotics is a global health threat. The study aimed to ascertain the Saccharomyces boulardii filter's impact on lowering the virulence of the bacterial species that cause diarrhea and the extent of genetic affinity between those organisms. Methods: 350 stool samples were investigated for all age groups who suffer from diarrhea, using biochemical and molecular methods. Results: Biochemical diagnosis were 2.28% for Salmonella and 0.57% for Enterobacter aerogenes, while molecular diagnosis didn't record any percentage for the mentioned bacteria, therefore molecular test was a better way to properly diagnose bacterial species, the causes of diarrhea are bacteria, viruses, parasites, medications, and toxins. The molecular identification of isolates by PCR technique and sequencing of 16S rDNA gene indicated that 12 isolates belonged to the genera Enterobacter cloacae, Cronobacter sakazakii, and Aeromonas hydrophila. The study revealed that there is a difference in the rates of resistance of isolates to some antibiotics before and after exposing them to probiotics. Where the percentage of antibiotic resistance was recorded before exposure to probiotics were piperacilline (91.6%), cefotaxime/clavulanic acid (41.6%), and tetracycline (25%), while the percentage of antibiotic resistance after exposure to probiotics were (58.3%) piperacillin, (0%) cefotaxime/clavulanic acid, and (0%) tetracycline. Where the resistance of bacteria to antibiotics decreases after exposing them to probiotics. Conclusion: The molecular diagnostic method is more accurate method to diagnose the bacterial species with complete accuracy. The Saccharomyces boulardii filter had an effective role in reducing or suppressing bacterial resistance against piperacillin, cefotaxime/clavulanic acid, and tetracycline, while it did not affect the bacterial resistance towards amoxicillin clavulanic acid. B Abstract www.als-journal.com/
... Yeasts constitute a minor component ( < 0.1%) of the total gut microbiota; however, because their size is 10 times larger than that of bacteria, they can exert steric hindrance on various bacterial species. 10 Blastocystis , a common intestinal protozoan, has been implicated in IBS development. Other contributory factors include family history, maltreatment, bullying, and gender disparities. ...
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Background Irritable bowel syndrome (IBS) is a prevalent lifestyle-associated ailment linked to the gut microbiota that significantly influences patients' quality of life. A notable correlation exists between Blastocystis infections and susceptibility to IBS, with infected individuals exhibiting an increased likelihood of developing the condition. Despite promising results from using probiotics to modulate the gut microbiota and manage IBS, the precise mechanisms and potential risks remain unclear. Objective This review aims to explore the therapeutic potential of probiotics, particularly Saccharomyces boulardii, in the management of IBS, highlighting the role of the gut microbiota and the gut–brain axis in IBS pathophysiology. Methods A comprehensive literature survey was conducted to examine the association between gut microbiota and IBS, the role of probiotics in managing IBS, the mechanisms of their action, and the potential risks associated with their long-term use. Additionally, this study addresses the influence of Blastocystis infections on IBS susceptibility and evaluates various ongoing clinical trials investigating probiotic use for IBS. Results S boulardii, a yeast species with probiotic properties, has demonstrated effectiveness in both the treatment and prophylaxis of IBS. Its administration is associated with a decrease in the proinflammatory cytokine interleukin 8 and an increase in the anti-inflammatory cytokine interleukin 10. Probiotics appear to function by inhibiting the growth of pathogenic microorganisms and regulating neurotransmitter activity, influencing the gut–brain axis. However, selecting appropriate probiotic strains and dosing regimens is crucial because of potential adverse effects, such as infections and allergic reactions. Conclusions Probiotics, specifically S boulardii, offer a promising avenue for IBS management by modulating gut microbiota. However, further research is necessary to delineate the precise mechanisms of action, optimal strains, dosing regimens for IBS treatment, and potential risks associated with long-term use. A comprehensive approach incorporating probiotics, a low-FODMAP diet, and cognitive-behavioral therapy may provide effective management of IBS symptoms.
... In the past decade, probiotics have emerged as one of the most notable alternatives to the subtherapeutic use of antibiotics due to reported health benefits for humans and animals [8]. Probiotics are yeast or bacteria, and variations within the two classes are attributed to the strains used. ...
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The primary objective of this study was to evaluate the potential immunomodulatory effect of maternal supplementation of Saccharomyces cerevisiae var. boulardii (Scb) from late gestation until the end of lactation on the immune phenotype of her progeny. Eighteen sows were fed 2 boluses per day of Saccharomyces cerevisiae var. boulardii CMCN-1079 (probiotic; PRO, n = 9) or placebo (CON, n = 9) starting at gestational day (GD) 84 and continuing until 21 days post-farrowing (end of lactation). Sow blood samples were collected every 7 days post-supplementation during gestation and 24-h post-farrowing and end of lactation. Blood samples were taken from 84 female pigs (n = 42 per sow treatment group) at 1, 7, 14, 21, 28, and 35 days old to assess innate and adaptive immune measures. Minimal effects of Scb supplementation were found on sow immune status during gestation and lactation, except for PRO-treated sows that had enhanced neutrophil function (P < 0.05) overall and mitogen-induced lymphocyte proliferation after 51 days of treatment (P < 0.0001). Overall, pigs from PRO-treated sows had higher C5a- and IL-8-induced neutrophil chemotaxis, NK cytotoxicity, and mitogen-induced B-lymphocyte proliferation than those from CON sows (P < 0.05; TRT). Supplementation had minimal effect on the sows but postnatal maternal exposure to Saccharomyces cerevisiae var. boulardii supplementation modulated the immune status of the progeny beyond the lactation period resulting in those from PRO-treated sows having more enhanced neutrophil function and B-cell proliferative response in the short term. Therefore, these data imply that including yeast probiotics in maternal diets may have carry-over effects in priming offspring’s immune function, especially neutrophil function and B-cell proliferation in the short term.
... Ruminococcaceae family can utilize yeast cell wall components, such as mannose, chitin, 1,3-β-glucan and 1,6-β-glucan(Czerucka et al., 2007), as fermentation substrates to produce SCFAs. As key bacterial metabolites produced by gut bacteria, SCFAs play a crucial role in linking microbiota composition and various biological effects at the mucosal level. ...
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Neonatal calves have a limited capacity to initiate immune responses due to a relatively immature adaptive immune system, which renders them susceptible to many on-farm diseases. At birth, the mucosal surfaces of the intestine are rapidly colonized by microbes in a process that promotes mucosal immunity and primes the development of the adaptive immune system. In a companion study, our group demonstrated that supplementation of a live yeast probiotic, Saccharomyces cerevisiae boulardii (SCB) CNCM I-1079, to calves from birth to 1 week of age stimulates secretory IgA (sIgA) production in the intestine. The objective of the study was to evaluate how SCB supplementation impacts the intestinal microbiota of one-week-old male calves, and how changes in the bacterial community in the intestine relate to the increase in secretory IgA. A total of 20 calves were randomly allocated to one of two treatments at birth: Control (CON, n = 10) fed at 5 g/d of carrier with no live yeast; and SCB (n = 10) fed at 5 g of live SCB per day (10 × 109 CFU/d). Our study revealed that supplementing calves with SCB from birth to 1 week of age had its most marked effects in the ileum, increasing species richness and phylogenetic diversity in addition to expediting the transition to a more interconnected bacterial community. Furthermore, LEfSe analysis revealed that there were several differentially abundant taxa between treatments and that SCB increased the relative abundance the family Eubacteriaceae, Corynebacteriaceae, Eggerthellaceae, Bacillaceae, and Ruminococcaceae. Furthermore, network analysis suggests that SCB promoted a more stable bacterial community and appears to reduce colonization with Shigella. Lastly, we observed that the probiotic-driven increase in microbial diversity was highly correlated with the enhanced secretory IgA capacity of the ileum, suggesting that the calf’s gut mucosal immune system relies on the development of a stable and highly diverse microbial community to provide the necessary cues to train and promote its proper function. In summary, this data shows that supplementation of SCB promoted establishment of a diverse and interconnected microbiota, prevented colonization of Escherichia Shigella and indicates a possible role in stimulating humoral mucosal immunity.
... Most probiotic yeast research focuses on Saccharomyces cerevisiae var. boulardii, the only species of yeast that has been tested well and is widely used as a probiotic [6][7][8][9]. However, more and more research is focused on the search for new strains with probiotic properties, not only Saccharomyces cerevisiae var. ...
Article
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One approach towards maintaining healthy microbiota in the human gastrointestinal tract is through the consumption of probiotics. Until now, the majority of probiotic research has focused on probiotic bacteria, but over the last few years more and more studies have demonstrated the probiotic properties of yeast, and also of species besides the well-studied Saccharomyces cerevisiae var. boulardii. Probiotic strains have to present the ability to survive in harsh conditions of the host body, like the digestive tract. Must fermentation might be an example of a similar harsh environment. In the presented study, we examined the probiotic potential of 44 yeast strains isolated from Polish wines. The tested isolates belonged to six species: Hanseniaspora uvarum, Pichia kluyveri, Metschnikowia pulcherrima, Metschnikowia ziziphicola, Saccharomyces cerevisiae and Starmerella bacillaris. The tested strains were subjected to an assessment of probiotic properties, their safety and their other properties, such as enzymatic activity or antioxidant properties, in order to assess their potential usefulness as probiotic yeast candidates. Within the most promising strains were representatives of three species: H. uvarum, M. pulcherrima and S. cerevisiae. H. uvarum strains 15 and 16, as well as S. cerevisiae strain 37, showed, among other features, survivability in gastrointestinal tract conditions exceeding 100%, high hydrophobicity and autoaggregation, had no hemolytic activity and did not produce biogenic amines. The obtained results show that Polish wines might be a source of potential probiotic yeast candidates with perspectives for further research.
... Isolate of P. kudriavzevii stand out because they have been isolated from different substrates and have the potential for use as probiotics for humans (Chelliah et al. 2016;Saadat et al. 2020). Saccharomyces is the most used probiotic yeast for humans (Czerucka et al. 2007) and cattle (Garcia-Mazcorro et al. 2020). However, no yeast isolated in this study belongs to this genus. ...
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The use of yeasts as a feed supplement for cattle can promote animal development and performance. However, for the positive results to be consistent, strains with probiotic properties must be selected. The objective of this study was to isolate and identify yeasts present in the bovine feces and evaluate their probiotic potential together with strains previously isolated from the rumen (preliminary study). A total of 193 isolates were studied, including 139 isolates (19 species) from fecal samples from 11 different animals (Bos taurus and Bos indicus) and 54 strains previously isolated from rumen fluid (Bos taurus). The yeast population in the feces ranged from 3.51 to 4.99 log CFU/g, with Candida pararugosa being the most abundant (isolated from the feces of six samples analysed). Isolates were selected that had negative results in the safety tests (hemolytic activity, DNAse, and gelatinase) and had percentages greater than 35 and 70% for hydrophobicity and auto-aggregation, respectively. In addition, selected isolates had percentages greater than 77.7 and 74.7% for coaggregation with pathogenic strains of Escherichia coli and Clostridium perfringens, respectively. The isolates with percentage growth at 39 °C greater than 64.6% and viability greater than 96.7% were selected for survival testing under bovine gastrointestinal conditions. After the tests, the seven best isolates were selected, belonging to the species Candida pararugosa (L60, CCMA 928 and CCMA 930) and Pichia kudriavzevii (L97, L100, CCMA904, CCMA 907). The selected isolates were exopolysaccharide producers. Based on the results of the evaluated properties, the seven selected isolates were classified as potential probiotics for cattle.
... Health benefits have been predominantly demonstrated for specific probiotic strains of the bacteria genera Lactobacillus, Bifidobacterium, Enterococcus, Streptococcus, Pediococcus, Leuconostoc, and Bacillus (Staniszewski and Kordowska-Wiater 2021), while one strain of yeast, S. cerevisiae var. boulardii, has been found to be an effective probiotic in double-blind clinical studies (Czerucka et al. 2007) and there is a need to further study in detail about this yeast and other potential ones. And also increasing multidrug resistant pathogens, increased demand for natural drug substitutes, and the emergence of scientific and clinical evidences demonstrating the efficacy of probiotics have prompted researchers to investigate probiotics as alternative remedies (Khagwal et al. 2019). ...
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This study aimed to isolate and characterize potential probiotic yeasts from Ethiopian injera sourdough and the study was conducted by collecting samples from Gondar and Bahir Dar cities, Ethiopia. The potential yeasts were isolated and identified using morphological, physiological, biochemical and molecular based analysis. Promising isolates were selected to further investigate their in vitro probiotic properties, including survival at different temperatures (25, 30, 37, and 42 °C), acidic pH (2, 3, 4 and 5), bile salt (0.1, 0.3, and 0.5%), and osmotolerance (20, 30, 40, and 50% glucose concentration), antimicrobial activities, proteolytic and lipolytic activities as well as resistance to four antibiotics. From 20 samples, 38 isolates were obtained. Among these, 10 produced low or non-hydrogen sulfide and were selected for further work. Further screening tests revealed that five isolates (G1N1, G2N4, G3N1, G8N1, and B6N3) were able tolerate and grow at 37 °C, with harsh conditions of the human digestive tract like low pH, bile salt, and higher osmotic effect. The maximum growth OD values were recorded at 37 °C by isolate G4N1 (OD value (0.6667), while G3N1 exhibited a maximum growth OD value of 0.4227 at pH 2. On the other hand, G2N4 gave a maximum OD value of 0.8800 at 0.3% bile salt concentration. The promising isolates were sequenced and identified to species level. Based on phylogenetic tree analysis, all the five probiotic yeast isolates had one common ancestor and belonging to Saccharomyces cerevisiae (G1N1 and G2N4), Candida humilis (G3N1 and B6N3), and Pichia kudriavzevii (G8N1). This study revealed that Ethiopian injera sourdough could be potential source of different probiotic yeast strains. Strong emphasis should be given about the use of probiotic yeasts that are isolated from Ethiopian fermented foods.
... Saccharomyces cerevisiae var. boulardii (Sb) is a yeast used in preparations with proven probiotic efficacy (McFarland, 2006;Beaugerie and Petit, 2004;Czerucka et al., 2007;Agarbati et al., 2020). Potentially probiotic yeast can be used to produce various fermented foods, improving their nutritional and organoleptic properties (Staniszewski and Kordowska-Wiater, 2021). ...
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The potential probiotic yeast was isolated from the Kyzyl Anor pomegranate variety growing in the Turkestan region (Kazakhstan). The yeast strain was identified as Saccharomyces cerevisiae Az-12. Molecular genetic identification was carried out using the Sanger sequencing method. The degree of homology of the S. cerevisiae Az-12 strain with the strain MH608341.1 Saccharomyces cerevisiae isolate extr03 was 99.65%. Antagonistic effect of the yeast against pathogenic bacteria was confirmed according inhibition zones for Staphylococcus aureus 13.5 ± 0.05 mm; the inhibition zones for Escherichia coli 12.8 ± 0.05 mm; and 10.7 ± 0.05 mm for Pseudomonas aeruginosa. Scanning microscopy of S. cerevisiae Az-12 and S. aureus confirmed the adhesive ability of the yeast cell surface to S. aureus. S. cerevisiae Az-12 were chosen as the most promising, as they are able to quickly ferment juices. Functional drinks containing pomegranate juice and yeast with a probiotic effect can be considered as a useful synbiotic product formulation.
... Как дрожжевые пробиотики, S. boulardii отличаются от бактериальных пробиотиков физиологической структурой, размером, отсутствием резистентности и чувствительности к антибактериальным препаратам [18]. S. boulardii имеют несколько различных механизмов действия, которые можно разделить на три основные группы: люминальное действие (действие в просвете кишечника), трофическое действие и слизисто-противовоспалительное сигнальное действие [15,16,19]. ...
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The human intestine is a complex ecosystem inhabited by bacteria, fungi, archaea, and viruses. However, the study of the intestinal microbiome attracts the most attention because of the abundance of bacteria. At the same time, given the diversity of microorganisms belonging to different kingdoms and coexisting in the same biotopes, studying only bacteria is a way to misunderstand the complexity of the processes occurring in the digestive tract. In this context, it is relevant to study the fungi inhabiting the digestive tract as participants in physiological and pathological processes in the host organism, as well as the therapeutic possibilities of individual representatives of the fungus kingdom. In this regard, of particular interest is Saccharomyces boulardii, a type of fungus that has a multifaceted effect on the human immune system, inhibiting the growth of bacterial pathogens and modulating the permeability of the digestive tract mucosa, which determines its active use as a probiotic in acute and chronic gastrointestinal diseases. Key words: Saccharomyces boulardii, probiotics, inflammatory bowel diseases, diarrhea, antibiotic-associated diarrhea, irritable bowel syndrome
... The technologies developed for genome editing of Saccharomyces cerevisiae can be applied almost as they are (6,7). S. boulardii has been reported as highly resistant to environmental stresses such as acidity and body temperature compared to many other bacteria and yeast (4,7,8), and can secrete recombinant proteins in the intestine (9). As S. boulardii is thoroughly washed out of the intestine within 3 to 4 days after cessation of oral administration, the supply of recombinant protein can be easily controlled (6). ...
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The probiotic yeast Saccharomyces boulardii has great potential for use as a chassis for microbiome engineering because of its high resistance to environmental stress, well-developed genetic tools, and the ability to secrete recombinant proteins in the intestine. As oral feeding of lysozyme has been reported to change the gut microbiome and fecal metabolites, we engineered S. boulardii to secrete human lysozyme, and investigated the changes in the microbiome and fecal metabolites in response to the administration of the engineered probiotic yeast into mice. Administration of S. boulardii changed the structure of the gut microbiome by promoting the growth of clostridia and increasing the diversity of strains. The human lysozyme secreted by S. boulardii in the intestine resulted in a unique gut microbiome structure through selective growth. In addition, the administration of probiotic yeast S. boulardii affected host energy metabolism and decreased blood urea and fructose levels, suggesting a mechanism of health benefits in mice. IMPORTANCE Our study identified changes in the microbiome by administering wild-type S. boulardii in mice to healthy mice based on long-read sequencing and demonstrated that a recombinant protein secreted by engineered S. boulardii in the intestine could change the microbiome. Our results provide valuable information for the development of therapeutics using engineered S. boulardii that changes the gut microbiome and host physiology.
... Given the function of maintaining intestinal flora balance and trophic intestinal effects, S. boulardii has been extensively researched and applied for the prevention and combate of acute and chronic enterocolopathies, antibiotic-associated diarrhea, traveler's diarrhea and Clostridium difficile infections (Szajewska and Kolodziej, 2015;Sivananthan and Petersen, 2018). Pharmacokinetics studies have shown that oral treatment with a lyophilized preparation of S. boulardii produces a stable concentration in the colon within 3 days, while it cannot be detected in feces in 2-5 days after discontinuation (Czerucka et al., 2007). It has shown that the use of S. boulardii in the treatment of diarrhea was safe and could reduce the time and frequency of diarrhea (Feizizadeh et al., 2014). ...
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... L. mesenteroides has been cited for their probiotic properties in several studies (Eom et al., 2008;Chun et al., 2017;Yi et al., 2017). Furthermore, the viability of LAB in the distal gut from the stock of fermented vegetables consumed is dependent upon storage time, tolerance to low pH, bile salts, salivary enzymes, gastric juices, and adaptation to body temperature (Czerucka et al., 2007;Menezes et al., 2020;Chan et al., 2021). Thus, as L. mesenteroides was seen in 7 out of 23 consumers, its presence in consumers' faeces needs to be evaluated relative to the time of consumption, but also in the context of how successfully it can reach the distal colon across different individuals and populations. ...
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... Specific probiotic strains of Bacillus, Bifidobacterium, Enterococcus, Escherichia, Lactobacillus, Leuconostoc, Pediococcus and Streptococcus bacterial genera are given as examples of probiotic microorganisms. Also, Saccharomyces is the only yeast genus proven to be probiotic (Gibson and Roberfroid, 1995;Jin et al., 2000;Alvarez-Olmos and Oberhelman, 2001;Czerucka et al., 2007;Gupta and Garg, 2009;Fijan, 2014). The 2 most common types of probiotic bacteria used in foods are Bifidobacterium and Lactobacillus. ...
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... Enam isolat ini memiliki kemiripan karakter atau teridentifikasi sebagai anggota genus Kluyveromyces, Pichia, dan Saccharomyces berdasarkan karakter makroskopis, mikroskopis, reproduksi sel dan uji fisiologi (Tabel 3.2). Czerucka et al. (2007) menyatakan bahwa standar uji probiotik pada khamir dapat menghambat laju pertumbuhan bakteri patogen opurtunistik E. coli pada saluran pencernaan dan suhu 37 0 C sesuai dengan suhu tubuh pada manusia. ...
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Saccharomyces boulardii is the unique yeast probiotic which can grow under aerobic or anaerobic conditions and generates CO2. In present investigation this property of yeast used to develop floating drug delivery system by entrapping generated in situ CO2 gas. Valsartan is a highly selective and orally active antihypertensive drug which has absorption window in the acidic environment of stomach. Central composite design response surface methodology technique used, so as to explore the effect of formulation variables such as amount of Saccharomyces boulardii preparation and calcium hydroxide on floating lag time and % drug release after 12 h. An optimal formulation selected using numerical and graphical optimization technique Valsartan formulation containing this novel floating agent is suitable for gastro retention and it increases its bioavailability. The experimental values and predicted values of an optimized batch are in compliance with each other.
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Background and purpose: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. The aim of this study was to examine the protective effects of the probiotic S. boulardii CNCM I-745 in a rat model of diclofenac-induced enteropathy. Experimental approach: Enteropathy was induced in 40-wk-old male rats by intragastric diclofenac (4 mg/kg BID for 14 days). S. boulardii CNCM I-745 (3 g/kg BID by oral gavage) was administered starting 14 days before (preventive protocol) or in concomitance (curative protocol) with diclofenac administration. Ileal damage, inflammation, barrier integrity, gut microbiota composition, and TLRs-NF-kB-pathway were evaluated. Key results: Diclofenac elicited intestinal damage, along with increments of myeloperoxidase, malondialdehyde, tumor necrosis factor and interleukin-1β, overexpression of TLR-2/-4, MyD88, and NF-kB p65, increased faecal calprotectin and butyrate levels as well as a decrease in blood hemoglobin levels, occludin and butyrate transporter MCT1 expression. In addition, diclofenac provoked a shift of bacterial taxa in both faecal and ileal samples. Treatment with S. boulardii CNCM I-745, in both preventive and curative protocol, counteracted the majority of these deleterious changes. Only preventive administration of the probiotic counteracted NSAID-induced decreased expression of MCT1 and increase in faecal butyrate levels. No significant changes were observed for the occludin expression after probiotic treatment. Conclusion and implications: Treatment with S. boulardii CNCM I-745 prevents diclofenac-induced enteropathy through anti-inflammatory and antioxidant activities. Such effects are likely to be related to increased tissue butyrate bioavailability, through an improvement of butyrate uptake by the enteric mucosa.
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Salmonella spp. is one of the most important foodborne pathogens. Typhoid fever and enteritis caused by Salmonella enterica are associated with 16-33 million infections and 500,000 to 600,000 deaths annually worldwide. The eradication of Salmonella is becoming increasingly difficult because of its remarkable capacity to counter antimicrobial agents. In addition to the intrinsic and acquired resistance of Salmonella, increasing studies indicated that its non-inherited resistance, which commonly mentioned as biofilms and persister cells, plays a critical role in refractory infections and resistance evolution. These remind the urgent demand for new therapeutic strategies against Salmonella. This review starts with escape mechanisms of Salmonella against antimicrobial agents, with particular emphasis on the roles of the non-inherited resistance in antibiotic failure and resistance evolution. Then, drug design or therapeutic strategies that show impressive effects in overcoming Salmonella resistance and tolerance are summarized completely, such as overcoming the barrier of outer membrane by targeting MlaABC system, reducing persister cells by limiting hydrogen sulfide, and applying probiotics or predatory bacteria. Meanwhile, according to the clinical practice, the advantages and disadvantages of above strategies are discussed. Finally, we further analyze how to deal with this tricky problems, thus can promote above novel strategies to be applied in the clinic as soon as possible. We believed that this review will be helpful in understanding the relationships between tolerance phenotype and resistance of Salmonella as well as the efficient control of antibiotic resistance.
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The purpose of this review was to summarize and analyze information on the molecular geneticbasis and methods for studying the probiotic activities of Saccharomycetes fungi, the mechanisms of theirphysiological action, and their application in biotechnology. The relevance of research in this area is con-firmed by the dynamics of the growth of publications. The effectiveness of Saccharomyces boulardii in thetreatment and prevention of diarrhea of various etiologies, relapses of Clostridium difficile infection, and theside effects of Helicobacter pylori infection therapy has been established with a high level of evidence. Thegenetic, cytological, cultural, and biochemical features of S. boulardii determine its probiotic activities. OtherSaccharomyces strains with probiotic potential are most often isolated from national fermented plant anddairy products. A unified methodology for studying the probiotic properties of yeast has not yet been created;clinical trials involving people are needed to confirm their status. Strains of the species Saccharomyces cere-visiae and Kluyveromyces marxianus, which have an international safety status, are promising probiotics. Pos-sible mechanisms of the physiological actions of Saccharomycetes include antimicrobial and antitoxic, tro-phic, antisecretory and anti-inf lammatory effects. Some of the mechanisms of yeast probiotic action differfrom those of bacteria, and not all of them are as yet understood. Saccharomycetes probiotics can be used toimprove the biological value, quality, and safety of food products.
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The possible role of Saccharomyces boulardii, a nonpathogenic yeast with beneficial effects on the human intestine, in the maintenance treatment of Crohns disease has been evaluated. Thirty-two patients with Crohns disease in clinical remission (CDAI < 150)="" were="" randomly="" treated="" for="" six="" months="" with="" either="" mesalamine="" 1="" g="" three="" times="" a="" day="" or="" mesalamine="" 1="" g="" two="" times="" a="" day="" plus="" a="" preparation="" of="">Saccharomyces boulardii 1 g daily. Clinical relapses as assessed by CDAI values were observed in 37.5% of patients receiving mesalamine alone and in 6.25% of patients in the group treated with mesalamine plus the probiotic agent. Our results suggest that Saccharomyces boulardii may represent a useful tool in the maintenance treatment of Crohns disease. However, in view of the products cost, further controlled studies are needed to confirm these preliminary data.
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In fungi and many other organisms, a thick outer cell wall is responsible for determining the shape of the cell and for maintaining its integrity. The budding yeast Saccharomyces cerevisiae has been a useful model organism for the study of cell wall synthesis, and over the past few decades, many aspects of the composition, structure, and enzymology of the cell wall have been elucidated. The cell wall of budding yeasts is a complex and dynamic structure; its arrangement alters as the cell grows, and its composition changes in response to different environmental conditions and at different times during the yeast life cycle. In the past few years, we have witnessed a profilic genetic and molecular characterization of some key aspects of cell wall polymer synthesis and hydrolysis in the budding yeast. Furthermore, this organism has been the target of numerous recent studies on the topic of morphogenesis, which have had an enormous impact on our understanding of the intracellular events that participate in directed cell wall synthesis. A number of components that direct polarized secretion, including those involved in assembly and organization of the actin cytoskeleton, secretory pathways, and a series of novel signal transduction systems and regulatory components have been identified. Analysis of these different components has suggested pathways by which polarized secretion is directed and controlled. Our aim is to offer an overall view of the current understanding of cell wall dynamics and of the complex network that controls polarized growth at particular stages of the budding yeast cell cycle and life cycle.
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In this study, we describe a novel murine model of chronic intestinal inflammation induced by the hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB/c and SJL/J mice resulted in a chronic transmural colitis with severe diarrhea, weight loss, and rectal prolapse, an illness that mimics some characteristics of Crohn's disease in humans. The colon of TNBS-treated mice on day 7 was marked by infiltration of CD4+ T cells; furthermore, in situ polymerase chain reaction studies revealed high levels of interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria (LP) CD4+ T cells from TNBS-treated mice stimulated with anti-CD3 and anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a 20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease in IL-4 levels as compared with those of stimulated LP CD4+ T cells from control BALB/c mice. Administration of monoclonal anti-IL-12 antibodies to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after induction of colitis led to a striking improvement in both the clinical and histopathological aspects of the disease and frequently abrogated the established colitis completely. Furthermore, LP CD4+ T cells isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon in vitro stimulation. In summary, the data demonstrate the pivotal role of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic intestinal inflammation. Furthermore, they suggest the potential utility of anti-IL-12 antibodies in patients with Crohn's disease.
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To determine the safety and efficacy of a new preventive agent for antibiotic-associated diarrhea (AAD) in patients receiving at least one beta-lactam antibiotic. A double-blinded, placebo-controlled, parallel group study was performed in a high-risk group of hospitalized patients receiving a new prescription for a beta-lactam antibiotic and having no acute diarrhea on enrollment. Lyophilized Saccharomyces boulardii or placebo (1 g/day) was given within 72 h of the start of the antibiotic(s) and continued until 3 days after the antibiotic was discontinued, after which the patients were followed for 7 wk. Of the 193 eligible patients, significantly fewer, 7/97 (7.2%), patients receiving S. boulardii developed AAD compared with 14/96 (14.6%) on placebo (p = 0.02). The efficacy of S. boulardii for the prevention of AAD was 51%. Using a multivariate model to adjust for two independent risk factors for AAD (age and days of cephalosporin use), the adjusted relative risk was significantly protective for S. boulardii (RR = 0.29, 95% CI = 0.08, 0.98). The prophylactic use of S. boulardii given with a beta-lactam antibiotic resulted in a significant reduction of AAD with no serious adverse reactions.
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OBJECTIVE--To determine the safety and efficacy of a new combination treatment for patients with Clostridium difficile-associated disease (CDD). The treatment combines the yeast Saccharomyces boulardii with an antibiotic (vancomycin hydrochloride or metronidazole). DESIGN--A double-blind, randomized, placebo-controlled, parallel-group intervention study in patients with active CDD. Patients received standard antibiotics and S boulardii or placebo for 4 weeks, and were followed up for an additional 4 weeks after therapy. Effectiveness was determined by comparing the recurrence of CDD in the two groups using multivariate analysis to control for other risk factors for CDD. SETTING--National referral study of ambulatory or hospitalized patients from three main study coordinating centers. PATIENTS--A total of 124 eligible consenting adult patients, including 64 who were enrolled with an initial episode of CDD, and 60 who had a history of at least one prior CDD episode. Patients who were immunosuppressed due to acquired immunodeficiency syndrome or cancer chemotherapy within 3 months were not eligible. INTERVENTION--Treatment with oral S boulardii (1 g/d for 4 weeks) or placebo in combination with a standard antibiotic. MAIN OUTCOME MEASURE--Recurrence of active CDD. RESULTS--A history of CDD episodes dramatically increased the likelihood of further recurrences. Multivariate analysis revealed that patients treated with S boulardii and standard antibiotics had a significantly lower relative risk (RR) of CDD recurrence (RR, 0.43; 95% confidence interval, 0.20 to 0.97) compared with placebo and standard antibiotics. The efficacy of S boulardii was significant (recurrence rate 34.6%, compared with 64.7% on placebo; P = .04) in patients with recurrent CDD, but not in patients with initial CDD (recurrence rate 19.3% compared with 24.2% on placebo; P = .86). There were no serious adverse reactions associated with S boulardii. CONCLUSIONS--The combination of standard antibiotics and S boulardii was shown to be an effective and safe therapy for these patients with recurrent CDD; no benefit of S boulardii was demonstrated for those with an initial episode of CDD.
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Saccharomyces boulardii is a nonpathogenic yeast used for the prevention and treatment of Clostridium difficile-associated diarrhea and colitis. However, the mechanism by which S. boulardii exerts its protective effects remains unclear. The binding of [3H]toxin A to its brush border receptor preincubated with S. boulardii-cultured suspension or filtered conditioned medium was measured in vitro. The effect of toxin A on secretion, epithelial permeability, and morphology in rat ileal loops in vivo was also examined in rats pretreated with S. boulardii. S. boulardii reduced [3H]toxin A-receptor binding in a dose-dependent fashion. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of ileal brush border exposed to S. boulardii-conditioned medium revealed a diminution of all brush border proteins. Treatment of rats with S. boulardii suspension reduced fluid secretion and mannitol permeability caused by toxin A. S. boulardii may reduce some of the enterotoxic effects of toxin A by inhibiting toxin A-receptor binding. This effect appears to be manifested by a secreted product of the yeast, possibly a protease.
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Saccharomyces boulardii, a nonpathogenic yeast, is effective in treating some patients with Clostridium difficile diarrhea and colitis. We have previously reported that S. boulardii inhibits rat ileal secretion in response to C. difficile toxin A possibly by releasing a protease that digests the intestinal receptor for this toxin (C. Pothoulakis, C. P. Kelly, M. A. Joshi, N. Gao, C. J. O'Keane, I. Castagliuolo, and J. T. LaMont, Gastroenterology 104: 1108-1115, 1993). The aim of this study was to purify and characterize this protease. S. boulardii protease was partially purified by gel filtration on Sephadex G-50 and octyl-Sepharose. The effect of S. boulardii protease on rat ileal secretion, epithelial permeability, and morphology in response to toxin A was examined in rat ileal loops in vivo. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified S. boulardii protease revealed a major band at 54 kDa. Pretreatment of rat ileal brush border (BB) membranes with partially purified protease reduced specific toxin A receptor binding (by 26%). Partially purified protease digested the toxin A molecule and significantly reduced its binding to BB membranes in vitro (by 42%). Preincubation of toxin A with S. boulardii protease inhibited ileal secretion (46% inhibition, P < 0.01), mannitol permeability (74% inhibition, P < 0.01), and histologic damage caused by toxin A. Thus, S. boulardii protease inhibits the intestinal effects of C. difficile toxin A by proteolysis of the toxin and inhibition of toxin A binding to its BB receptor. Our results may be relevant to the mechanism by which S. boulardii exerts its protective effects in C. difficile infection in humans.
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As is the case for Saccharomyces boulardii, Saccharomyces cerevisiae W303 protects Fisher rats against cholera toxin (CT). The addition of glucose or dinitrophenol to cells of S. boulardii grown on a nonfermentable carbon source activated trehalase in a manner similar to that observed for S.cerevisiae. The addition of CT to the same cells also resulted in trehalase activation. Experiments performed separately on the A and B subunits of CT showed that both are necessary for activation. Similarly, the addition of CT but not of its separate subunits led to a cyclic AMP (cAMP) signal in both S. boulardii and S. cerevisiae. These data suggest that trehalase stimulation by CT probably occurred through the cAMP-mediated protein phosphorylation cascade. The requirement of CT subunit B for both the cAMP signal and trehalase activation indicates the presence of a specific receptor on the yeasts able to bind to the toxin, a situation similar to that observed for mammalian cells. This hypothesis was reinforced by experiments with 125I-labeled CT showing specific binding of the toxin to yeast cells. The adhesion of CT to a receptor on the yeast surface through the B subunit and internalization of the A subunit (necessary for the cAMP signal and trehalase activation) could be one more mechanism explaining protection against the toxin observed for rats treated with yeasts.
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Saccharomyces boulardii is a non-pathogenic yeast which exerts trophic effects on human and rat small intestinal mucosa. To examine the effects of S boulardii on ileal adaptation after proximal enterectomy in rats. Wistar rats, aged eight weeks, underwent 60% proximal resection or transection and received by orogastric intubation either 1 mg/g body wt per day lyophilised S boulardii or the vehicle for seven days. The effects on ileal mucosal adaptation were assessed eight days after surgery. Compared with transection, resection resulted in mucosal hyperplasia with significant decreases in the specific and total activities of sucrase, lactase, and maltase. Treatment of resected animals with S boulardii had no effect on mucosal hyperplasia but did upgrade disaccharidase activities to the levels of the transected group. Enzyme stimulation by S boulardii was associated with significant increases in diamine oxidase activity and mucosal polyamine concentrations. Likewise, sodium dependent D-glucose uptake by brush border membrane vesicles, measured as a function of time and glucose concentration in the incubation medium, was significantly (p<0.05) increased by 81% and three times respectively in the resected group treated with S boulardii. In agreement with this, expression of the sodium/glucose cotransporter-1 in brush border membranes of resected rats treated with S boulardii was enhanced twofold compared with resected controls. Oral administration of S boulardii soon after proximal enterectomy improves functional adaptation of the remnant ileum.
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Four cases of Saccharomyces boulardii fungemia, a very rare side effect of Saccharomyces boulardii therapy, are reported. The clinical impact of Saccharomyces boulardii infection appeared to be moderate. However, even though organ involvement was never demonstrated, septic shock with no other etiology was observed in one of our patients. All patients had an indwelling vascular catheter. Contamination of the air, environmental surfaces, and hands following the opening of a packet suggests that catheter contamination may have been a source of infection. To prevent catheter contamination it is recommended that packets or capsules of Saccharomyces boulardii be opened with gloves, outside the patient's room.
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Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NFkappaB), which is involved in their gene transcription, is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this effect by acting on proinflammatory cytokine expression. Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and mRNA levels. NFkappaB p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NFkappaB inhibitory protein (IkappaBalpha) were analysed by western blotting. The in vivo efficacy of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis. Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NFkappaB from the cytoplasm to the nucleus. LPS induced NFkappaB transcriptional activity was decreased by butyrate while IkappaBalpha levels were stable. Butyrate treatment also improved TNBS induced colitis. Butyrate decreases proinflammatory cytokine expression via inhibition of NFkappaB activation and IkappaBalpha degradation. These anti-inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.
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In fungi and many other organisms, a thick outer cell wall is responsible for determining the shape of the cell and for maintaining its integrity. The budding yeast Saccharomyces cerevisiae has been a useful model organism for the study of cell wall synthesis, and over the past few decades, many aspects of the composition, structure, and enzymology of the cell wall have been elucidated. The cell wall of budding yeasts is a complex and dynamic structure; its arrangement alters as the cell grows, and its composition changes in response to different environmental conditions and at different times during the yeast life cycle. In the past few years, we have witnessed a profilic genetic and molecular characterization of some key aspects of cell wall polymer synthesis and hydrolysis in the budding yeast. Furthermore, this organism has been the target of numerous recent studies on the topic of morphogenesis, which have had an enormous impact on our understanding of the intracellular events that participate in directed cell wall synthesis. A number of components that direct polarized secretion, including those involved in assembly and organization of the actin cytoskeleton, secretory pathways, and a series of novel signal transduction systems and regulatory components have been identified. Analysis of these different components has suggested pathways by which polarized secretion is directed and controlled. Our aim is to offer an overall view of the current understanding of cell wall dynamics and of the complex network that controls polarized growth at particular stages of the budding yeast cell cycle and life cycle.
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Objectives: The main objectives of the study were to reduce the stool frequency, to improve the stool consistency and to reduce the mean duration of diarrhea in days. Study Design: Prospective (case control) study Place and Duration of Study: This study was conducted at Govt. Sifwat Ghayur Shaheed Memorial (infectious diseases) Children Hospital, Peshawar from May to Oct. 2016 Materials and Methods: A total of 200 patients were equally divided into two groups, cases and controls, randomly and consecutively. The cases group was receiving saccharomyces boullardii in addition to the routine management, while the control group was just receiving the normal management. Children of age, range between 6 months to 5 years were included in the study. Children with recurrent or chronic diarrhea, acute dysentery, thalassaemia and congenital heart disease were excluded of the study. Results: The cases group had a mean duration of diarrhea of 3.23 days and control group 5.84 days. The difference in stool frequency, consistency and duration was statistically significant on day 3 between the two groups (0.008,0.000). Conclusion: The use of saccharomyces boulardii is a beneficial addition to the management of acute diarrhea, which is associated with speedy recovery by improving stools frequency and consistency as compared to the patients who do not received.
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Basic remarks: Among travellers to distant countries with a low socioeconomic status and poor hygiene, traveller's diarrhea is a major problem. Once this epidemiological fact had been recognized, intensive efforts were made to reduce the incidence of this illness by prophylactic medication. Among non-antibiotic substances investigated, Saccharomyces boulardii (SB) appeared to show promising results in earlier studies. Method: In a placebo-controlled, double-blind study, various dosages (250 mg and 1,000 mg SB) were administered prophylactically to 3,000 Austrian travellers to distant regions. Results: A significant reduction in the incidence of diarrhea was observed, with succcess depending directly on the rigorous use of the preparation. A tendency was noted for SB to have a varying regional effect, which was particularly marked in North Africa and in the Near-east (Turkey!); in addition, the effect also proved to be dose-dependent. The medication can be classified as low on side effects.
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In the present study, a total of 55 European probiotic products were evaluated with regard to the identity and the antibiotic resistance of the bacterial isolates recovered from these products. Bacterial isolation from 30 dried food supplements and 25 dairy products, yielded a total of 268 bacterial isolates selected from several selective media. Counts of food supplements showed bacterial recovery in 19 (63%) of the dried food supplements ranging from 10(3) to 10(6) CFU/g, whereas all dairy products yielded growth in the range of 10(5)-10(9) CFU/ml. After identification of the isolates using whole-cell protein profiling, mislabeling was noted in 47% of the food supplements and 40% of the dairy products. In six food supplements, Enterococcus faecium was isolated whereas only two of those products claim this species on their label. Using the disc diffusion method, antibiotic resistance among 187 isolates was detected against kanamycin (79% of the isolates), vancomycin (65%), tetracycline (26%), penicillinG (23%), erythromycin (16%) and chloramphenicol (11%). Overall, 68.4% of the isolates showed resistance against multiple antibiotics including intrinsic resistances. Initially, 38% of the isolated enterococci was classified as vancomycin resistant using the disc diffusion method, whereas additional broth dilution and PCR assays clearly showed that all E. faecium isolates were in fact vancomycin susceptible.
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Objective: To evaluate efficacy of probiotics in prevention and treatment of diarrhoea associated with the use of antibiotics. Design: Meta-analysis; outcome data (proportion of patients not getting diarrhoea) were analysed, pooled, and compared to determine odds ratios in treated and control groups. Identification: Studies identified by searching Medline between 1966 and 2000 and the Cochrane Library. Studies reviewed Nine randomised, double blind, placebo controlled trials of probiotics. Results: Two of the nine studies investigated the effects of probiotics in children. Four trials used a yeast (Saccharomyces boulardii), four used lactobacilli, and one used a strain of enterococcus that produced lactic acid. Three trials used a combination of probiotic strains of bacteria. In all nine trials, the probiotics were given in combination with antibiotics and the control groups received placebo and antibiotics. The odds ratio in favour of active treatment over placebo in preventing diarrhoea associated with antibiotics was 0.39 (95% confidence interval 0.25 to 0.62; P<0.001) for the yeast and 0.34 (0.19 to 0.61; P<0.01 for lactobacilli. The combined odds ratio was 0.37 (0.26 to 0.53; P<0.001) in favour of active treatment over placebo. Conclusions: The meta-analysis suggests that probiotics can be used to prevent antibiotic associated diarrhoea and that S boulardii and lactobacilli have the potential to be used in this situation. The efficacy of probiotics in treating antibiotic associated diarrhoea remains to be proved. A further large trial in which probiotics are used as preventive agents should look at the costs of and need for routine use of these agents.
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Background: Small-bowel resection in animals results in alterations of the morphology and functional adaptation in the remaining intestine. The aim of our study was to study the effect of Saccharomyces boulardii versus placebo in rats after 50% small-bowel resection. Methods: Sixty-three rats were assigned to one of three groups: small-bowel resection (n = 31), transected surgery controls (n = 16), or non-surgical controls (n = 16). Of the 31 rats with small-bowel resection, 15 were given S. boulardii (140 mg/dl), and 16 were given placebo. Intestinal markers measured included bacterial overgrowth (BO) on days 4 and 8 and translocation into mesenteric lymph nodes, liver, and spleen. Markers of small-bowel adaptation included histomorphology of the mucosa, protein content, and various brush-border enzymes (sucrase, glucoamylase, n-aminopeptidase). Results: In the jejunal mucosal samples on day 8, S. boulardii-treated rats showed a significant increase in protein content (58.3 ± 12 mg/10 cm) compared with placebo-treated rats (29.2 ± 1.8) or non-surgery controls (18.3 ± 1.2; P < 0.001). S. boulardii-treated rats also had significantly higher levels of all three brush-border enzymes. A significant increase of enzyme-specific activities was observed in the ileum of S. boulardii resected rats compared with the placebo resected group on day 4, and no significant differences were seen in the remnant ileum except an increase in protein content in S. boulardii-treated rats on day 8. Histomorphometric studies showed no differences in ileal villus height or translocation frequencies by day 8 in S. boulardii or placebo resected rats. Conclusions: These data indicate that, after resection, S. boulardii does not modify bacterial overgrowth or translocation frequency but does significantly enhance the functional adaptation of the remaining intestinal segments.
Article
In this study, we describe a novel murine model of chronic intestinal inflammation induced by the hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB/c and SJL/J mice resulted in a chronic transmural colitis with severe diarrhea, weight loss, and rectal prolapse, an illness that mimics some characteristics of Crohn's disease in humans. The colon of TNBS-treated mice on day 7 was marked by infiltration of CD4+ T cells; furthermore, in situ polymerase chain reaction studies revealed high levels of interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria (LP) CD4+ T cells from TNBS-treated mice stimulated with anti-CD3 and anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a 20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease in IL-4 levels as compared with those of stimulated LP CD4+ T cells from control BALB/c mice. Administration of monoclonal anti-IL-12 antibodies to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after induction of colitis led to a striking improvement in both the clinical and histopathological aspects of the disease and frequently abrogated the established colitis completely. Furthermore, LP CD4+ T cells isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon in vitro stimulation. In summary, the data demonstrate the pivotal role of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic intestinal inflammation. Furthermore, they suggest the potential utility of anti-IL-12 antibodies in patients with Crohn's disease.
Chapter
Healthy animals and humans have a natural microflora consisting of prokaryotic and eukaryotic microorganisms on their external and internal body surfaces: skin, upper respiratory tract, lower urogenital tract, oral cavity and gastrointestinal tract. The composition of the natural microflora in these natural microbial habitats is very complex and strictly determined by the local environmental conditions.
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In order to evaluate whether Saccharomyces boulardii (S.b.) might improve the tolerance of continuous enteral feeding in burn patients, the authors performed a randomized double-blind trial in 20 patients with major burns (20–70 % full-thickness burns) and receiving nasogastric tube-feeding for 8 to 28 days. Treatment with S.b., at a dose of 2 g per day, resulted in a significant decrease in the occurrence of diarrhea (patients given a placebo had diarrhea for 9,1 % of treatment days, compared to only 1,5 % in patients given S.b., p < 0.001). An improvement trend in the efficiency of enteral feeding was also noted as measured by the mean number of calories tolerated per day. This improvement was significant (p < 0.05) only during the second week of enteral feeding.
Chapter
The indigenous gastrointestinal microflora consists of microorganisms that normally inhabit the gastrointestinal tract. The indigenous microflora primes the host immune response so that it can respond more effectively to exogenous pathogens. Keywords: GI microflora; indigenous microflora; indigenous bacteria; gastrointestinal bacteria; natural antibodies; immunostimulation by indigenous bacteria; bacterial translocation; opportunistic infections
Article
In 1885 Louis Pasteur was the first to propose that the human immune system may be influenced by microorganisms. A large body of data has since been accumulated proving this assumption to be correct. Bacteria constitute the main constituents of the microbial flora of the human digestive tract and compounds of the bacterial cell wall have been shown to play an important role in the interaction of microbes with higher organisms. These components include peptidoglycan (PG) and lipopolysaccharide (LPS) of Gram-negative bacteria. Both types of molecules are potent activators of the human immune system and exert their activity through the induction of endogenous mediators which are endowed with biological activity. This review focuses on the structure and activity of LPS and PG and illustrates how these bacterial factors stimulate the immune cells resulting in desired physiological or dramatic pathophysiological responses of the host organism.
Article
Saccharomyces boulardii (S.b.) is largely used in Western European countries for the treatment of acute infectious enteritis and antibiotic-induced gastrointestinal disorders. To study the mechanisms of the protective effect of S.b. against enteral pathogen infection, we assessed the response of the intestinal secretion of secretory IgA (s-IgA) and of the secretory component of immunoglobulins (SC) to oral administration of high doses (0.5 mg/g body weight, three times per day) of S.b. cells in growing rats. S.b. cells (biological activity: 2.8 x 10(9) viable cells/100 mg) were administered daily by gastric intubation to weanling rats from day 14 until day 22 postpartum. Control groups received either 0.9% saline or ovalbumin following the same schedule. Expressed per milligram of cell protein, SC content was significantly increased in crypt cells isolated from the jejunum (48.5% vs saline controls, P less than 0.05) as it was in the duodenal fluid (62.8% vs saline controls, P less than 0.01) of rats treated with S.b. Oral treatment with S.b. had no effect on the secretion of SC by the liver. In the duodenal fluid of rats treated with S.b. cells, the mean concentration of s-IgA was increased by 56.9% (P less than 0.01) over the concentration of s-IgA measured in saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Saccharomyces boulardii, a nonpathogenic yeast, has been widely used in Europe to prevent antibiotic-associated diarrhea (AAD). We performed a prospective double-blind controlled study to investigate AAD in hospitalized patients and to evaluate the effect of S. boulardii, a living yeast, given in capsule form concurrently with antibiotics. Over 23 mo, 180 patients completed the study. Of the patients receiving placebo, 22% experienced diarrhea compared with 9.5% of patients receiving S. boulardii (p = 0.038). Risk factors found to be associated with AAD were multiple antibiotic combinations (containing clindamycin, cephalosporins, or trimethoprim-sulfamethoxazole) and tube feeding. Clostridium difficile, an anaerobe found in the stools of most patients with pseudomembranous colitis, was variably associated with AAD. We evaluated the role of C. difficile in AAD in the study population and found no significant association between the presence of C. difficile or cytotoxin with AAD. Approximately 33% of the patients without diarrhea harbored at least one C. difficile-positive stool and nearly 50% of these patients had detectable cytotoxin. Similar values were obtained in patients with diarrhea. Of C. difficile-positive patients, 31% (5/16) on placebo developed diarrhea compared with 9.4% (3/32) on S. boulardii; this difference was not statistically significant (p = 0.07). There were no discernable adverse effects of yeast administration. We conclude that S. boulardii reduces the incidence of antibiotic-associated diarrhea in hospitalized patients.
Article
To evaluate the response of the small intestinal mucosa to Saccharomyces boulardii (S.b.), a yeast widely used in some countries as an adjuvant drug with oral antimicrobial therapy, seven healthy adult volunteers were treated with high doses of lyophilized S.b. (250 mg four times per day) for 2 wk. A peroral jejunal suction biopsy was performed on days 0 and 15 of the study. Compared to the initial biopsy, histological examination of the posttrial biopsy revealed no morphological alteration nor change in villus height or crypt depth. After treatment, the specific activity (per U protein) of sucrase, lactase, and maltase was, respectively, increased by 82% (p less than 0.05) 77% (p less than 0.05), and 75% (p less than 0.05) over the basal activity of the enzymes measured on day 0, whereas mucosal protein content remained unchanged. Similar findings were found in the jejunum of adult rats treated for 5 days with either viable or killed S.b. cells. The changes in total enzyme activity (per jejunal segment) paralleled the changes in specific enzyme activity. In vitro assays on freshly prepared suspensions of S.b. (6.0 X 10(8) viable cells/ml) evidenced a high activity for sucrase (mean +/- SE: 8 364 +/- 1280 U X g X protein-1) but no maltase, neutral lactase, acid beta-galactosidase, or aminopeptidase activity. To determine whether treatment with S.b. could influence the incorporation rate of neutral lactase into the brush border membrane, 14-day-old sucklings treated either with saline or with S.b. were given intraperitoneally a dose of 20 microCi D-[1(14)C] glucosamine 3 hours before sacrifice.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
We compared the effects of four beta-lactam drugs with widely differing antibacterial and pharmacological properties on the composition of the intestinal flora. Cefoxitin, piperacillin, cefoperazone, and aztreonam were given intravenously for 9 days to healthy volunteers. Cefoperazone reduced the numbers of aerobic and anaerobic bacteria to undetectable levels. At the other extreme, cefoxitin had little effect on the normal flora. Aztreonam markedly reduced the numbers of aerobes, whereas piperacillin had a variable effect on both aerobic and anaerobic bacteria. There was extensive overgrowth of enterococci in subjects given cefoxitin or aztreonam, which have little activity against this species, and of yeasts in subjects given cefoperazone or piperacillin. Cefoperazone reached concentrations of 2,727 to 8,840 micrograms/g in the feces, whereas the other agents were generally undetectable. These results show that the new beta-lactam antibiotics produce widely varying effects on the fecal microflora after parenteral administration and that these effects are consistent with the antibacterial and pharmacological properties of the drugs.
Article
Saccharomyces boulardii is a yeast widely used in humans for the prevention and treatment of infectious enteritis and Clostridium difficile-associated enterocolopathies. After oral administration to human volunteers or growing rats, S. boulardii enhances markedly the expression of intestinal enzymes as well as the production of the polymeric immunoglobulin receptor by mechanisms that remain unknown. We have analyzed the role of the yeast polyamines as potential mediators in the intestinal trophic response. In weanling rats (d 20 to d 30), a daily dose of 100 mg of lyophilized S. boulardii produced significant (p < 0.025) increases in sucrase (157%) and maltase (47%) activities. This dose corresponded to a total oral load of 678 nmol of polyamines per day (spermidine; 376 +/- 32, spermine: 293 +/- 26, putrescine: 9.5 +/- 1.4 nmol/100 mg). Spermine, given orally to growing rats at doses nearly equivalent (500 nmol) to the load of polyamines provided by the yeast (678 nmol), reproduced similar enzymatic changes, including a 2.5-fold induction of sucrase, and enhanced maltase activity (+24%). Spermidine and spermine concentrations measured in the jejunal mucosa of treated rats were increased over matched controls by 21.4% (p < 0.005) and 21.9%, respectively (p < 0.002). After being centrifuged and filtered to discard residual yeast cells, 2-mL samples of jejunal and ileal fluid collected from S. boulardii-treated rats by intestinal flushing contained higher levels of spermidine (48 and 60%) and spermine (150 and 316%) than did control rats. Our data indicate that lyophilized S. boulardii exerts trophic effects on the small intestine that are likely mediated by the endoluminal release of spermine and spermidine.
Article
Mild or severe episodes of diarrhoea are the main side effects of antibiotic therapy. The major form of intestinal disorders is pseudomembranous colitis due to Cl. difficile. Among ecological means for control of these diarrhoea, which result from disruption of the intestinal ecosystem, several non-pathogenic microorganisms can be used in order to establish a new equilibrium; among the available microorganisms, S. boulardii is a non-pathogenic yeast, which has given rise to many experimental and clinical studies. Moreover, results of an in vitro study of susceptibilities to antibiotics of the available microorganisms are reported; for S. boulardii, these in vitro data confirm the bases of persistence of the organism in the gut during antibiotic therapy. Besides these in vitro data, experimental studies in animal models (gnotobiotic mice and hamsters with Cl. difficile colitis) have confirmed the potential effectiveness of S. boulardii in preventing the pathogenic effect of toxins A and B and in decreasing numbers of Cl. difficile colonies in the gut. Similarly, in intensive care unit patients, controlled prospective studies have shown that administration of S. boulardii prevented diarrhoea, pseudo-membranous colitis and intestinal translocation of gram-negative bacilli when combined with selective digestive decontamination.
Article
CD4+ T cells in the mouse can be subdivided into two fractions based on the level of expression of the CD45RB determinant. Previous studies have shown that these subsets are functionally distinct. We have further characterized the properties of these subpopulations in vivo by injecting them into C. B-17 scid mice. The animals restored with the CD45RBhighCD4+ T cell population developed a lethal wasting disease with severe mononuclear cell infiltrates into the colon and elevated levels of IFN-γ mRNA. In contrast, animals restored with the reciprocal CD45RBlow subset or with unfractionated CD4+ T cells did not develop the wasting or colitis. Importantly, the co-transfer of the CD45RBlow population with the CD45RBhigh population prevented the wasting disease and colitis. These data indicate that important regulatory interactions occur between the CD45RBhigh and CD45RBlowCD4+ T cell subsets and that disruption of this mechanism has fatal consequences.
Article
A comparative electrophoretic karyotyping study was performed with several certified authentic strains of the four species that could be distinguished by nuclear DNA (nDNA)-nDNA reassociation data within the sensu stricto group of the genus Saccharomyces. A multivariate analysis of the polymorphisms observed in pulsed-field gel electrophoretic profiles (numbers and molecular weights of separated units) revealed that the strains could be separated into four clusters that corresponded to the taxa that were distinguished on the basis of nDNA comparisons. Discrepancies between nDNA reassociation data and membership in the corresponding clusters were observed only with two strains of Saccharomyces paradoxus. Blind tests carried out with additional industrial strains confirmed the general validity of the statistical model created for comparison of karyotypes within the species included in Saccharomyces sensu stricto.
Article
The yeast Saccharomyces boulardii inhibits the secretion induced by cholera toxin (CT) in rat jejunum. The present study was aimed at unraveling the mechanism by which S. boulardii protects intestinal cells against CT. CT-induced adenosine 3',5'-cyclic monophosphate (cAMP) levels were measured by radioimmunoassay in intestinal epithelial cells IEC-6 or HT29-D4 cells exposed to whole yeast or to culture medium conditioned by S. boulardii (Sb-conditioned medium). Sb-conditioned medium significantly reduced CT-induced cAMP levels in IEC-6 cells. This effect was eliminated by heat treatment, trypsin hydrolysis, and trichloroacetic acid precipitation of Sb-conditioned medium. When conditioned medium was fractionated on polyacrylamide gel under nondenaturing conditions, neutralizing activity was shown to be associated with a 120-kilodalton protein. The neutralizing activity was not attributable to proteolytic activity against CT. Sb-conditioned medium reduced the amount of cAMP induced by CT as well as Escherichia coli thermolabile toxin or forskolin in HT29-D4 cells. The modulation of secretagogue-induced cAMP by Sb-conditioned medium did not occur in the presence of pertussis toxin. These results suggest that the neutralization of CT by S. boulardii is mediated by a specific yeast protein and involves a receptor that is negatively coupled to adenylate cyclase.
Article
In a randomized, single-center, double-blind, placebo-controlled pilot study, 20 patients with established Crohn's disease suffering from diarrhea and moderate complaints as measured by the BEST Index, were treated with the yeast preparation Saccharomyces boulardii (S.b.) in a dosage of 250 mg t.i.d., initially for two weeks in addition to the basic treatment. A reduction in the frequency of bowel movements (5.0 +/- 1.4 vs. 4.1 +/- 2.3 evacuations/day, p < 0.01) and in the BEST Index (193 +/- 32 vs. 168 +/- 59, p < 0.05) as compared to baseline was registered. After this initial phase, the patients were allocated in randomized order to the control group (n = 7) receiving placebo, or to the verum group (n = 10) receiving S.b.(250 mg t.i.d.) for 7 weeks, while the basic treatment was maintained. The group treated with S.b. showed a significant reduction in the frequency of bowel movements in the tenth week, to 3.3 +/- 1.2 evacuations per day, and in the BEST Index, to 107 +/- 85. In the control group taking placebo, however, this effect was not observed. By contrast, the frequency of bowel movements and the BEST Index rose again in the tenth week until reaching initial values (4.6 +/- 1.9 evacuations daily and 180 +/- 61, respectively). No adverse drug events were observed. In order to confirm these positive effects of S.b. in patients with Crohn's disease, further controlled multicenter trials in a larger patient population should be performed.
Article
Basic remarks: Among travellers to distant countries with a low socioeconomic status and poor hygiene, traveller's diarrhea is a major problem. Once this epidemiological fact had been recognized, intensive efforts were made to reduce the incidence of this illness by prophylactic medication. Among non-antibiotic substances investigated, Saccharomyces boulardii (SB) appeared to show promising results in earlier studies. Method: In a placebo-controlled, double-blind study, various dosages (250 mg and 1,000 mg SB) were administered prophylactically to 3,000 Austrian travellers to distant regions. Results: A significant reduction in the incidence of diarrhea was observed, with success depending directly on the rigorous use of the preparation. A tendency was noted for SB to have a varying regional effect, which was particularly marked in North Africa and in the Near-east (Turkey!); in addition, the effect also proved to be dose-dependent. The medication can be classified as low on side effects.
Article
The indigenous gastrointestinal (GI) tract microflora has profound effects on the anatomical, physiological and immunological development of the host. The indigenous microflora stimulates the host immune system to respond more quickly to pathogen challenge and, through bacterial antagonism, inhibits colonization of the GI tract by overt exogenous pathogens. Indigenous GI bacteria are also opportunistic pathogens and can translocate across the mucosal barrier to cause systemic infection in debilitated hosts.
Article
To assess the preventive effect of Saccharomyces boulardii on diarrhea in critically ill tube-fed patients and to evaluate risk factors for diarrhea. Prospective, multicenter, randomized, double-blind placebo-controlled study. Eleven intensive care units in teaching and general hospitals. Critically ill patients whose need for enteral nutrition was expected to exceed 6 days. S. boulardii 500 mg four times a day versus placebo. Diarrhea was defined by a semiquantitative score based on the volume and consistency of stools. A total of 128 patients were studied, 64 in each group. Treatment with S. boulardii reduced the mean percentage of days with diarrhea per feeding days from 18.9 to 14.2% [odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.50-0.90, P = 0.0069]. In the control group, nine risk factors were significantly associated with diarrhea: nonsterile administration of nutrients in open containers, previous suspension of oral feeding, malnutrition, hypoalbuminemia, sepsis syndrome, multiple organ failure, presence of an infection site, fever or hypothermia, and use of antibiotics. Five independent factors were associated with diarrhea in a multivariate analysis: fever or hypothermia, malnutrition, hypoalbuminemia, previous suspension of oral feeding, and presence of an infection site. After adjustment for these factors, the preventive effect of S. boulardii on diarrhea was even more significant (OR = 0.61, 95% CI = 0.44-0.84, P < 0.0023). S. boulardii prevents diarrhea in critically ill tube-fed patients, especially in patients with risk factors for diarrhea.
Article
The detection of lectin sites for mannose-sensitive adhesion in the outer membrane of Saccharomyces boulardii and the irreversible binding of both enteropathogenic Escherichia coli (EPEC) and salmonellae (serovar Salmonella Typhimurium and Salmonella Enteritidis) provided the motivation to carry out further investigations to find out whether also other enteric bacteria such as entero-haemorrhagic Escherichia coli (EHEC) and the DT 104 mutant of S. Typhimurium have the capacity for binding to the cell wall of this yeast. Reference strains and fresh isolates from clinical cases of EHEC infections as well as salmonellae of the DT 104 mutant were included in this study using the agglutination test. The results first of all showed that EHEC of the serogroup O 157 and the DT 104 mutant of S. Typhimurium were bound to the surface of Saccharomyces boulardii. Because these bacteria do not respond very well to drugs but most of the gastrointestinal infections are caused by them, the use of S. boulardii for treatment and prophylaxis could be an excellent alternative.
Article
Several reports have confirmed that the cooperative interaction between cAMP- and Ca2+-mediated transduction pathways may contribute to the stimulatory or inhibitory regulation of Cl- secretion in intestinal epithelium. Saccharomyces boulardii has been shown to inhibit cholera toxin-induced secretion in rat jejunum. We have identified a 120-kDa protein in medium conditioned by Saccharomyces boulardii that reduces cholera toxin-induced cAMP in intestinal cells. The present study evaluated the effect of medium conditioned by Saccharomyces boulardii on cAMP- and Ca2+-mediated Cl- secretion in T84 cells. Experiments performed with cAMP agonists revealed that 1 hr of preincubation of cells with medium conditioned by Saccharomyces boulardii was necessary to elicit a 40-50% reduction in receptor (cholera toxin, prostaglandin E2, and vasoactive intestinal polypeptide) and nonreceptor (forskolin) mediated cAMP synthesis and 125I efflux. Secretion induced by carbachol was inhibited when cells were pretreated for 1 hr with medium conditioned by Saccharomyces boulardii despite the absence of inhibition of Ins (1,4,5)P3. From this study we conclude that Saccharomyces boulardii exerts an inhibitory effect in vitro on Cl- secretion mediated through both cAMP- and Ca2+-mediated signaling pathways.
Article
Despite recent interest in therapeutic microorganisms taken orally, little is known about the pharmacodynamics of these agents in a target population of patients with disease. The present study reports the stool concentrations of Saccharomyces boulardii in a patient population with Clostridium difficile disease (CDD) and correlates stool concentrations with efficacy. Patients with recurrent CDD all received a 10-day standard antibiotic regimen together with 28 days of S. boulardii or placebo. Stool samples were collected from patients at various time points and assayed for S. boulardii. The mean concentration of S. boulardii of patients who recurred was 2.5 x 104 CFU/g compared to 1 x 106 CFU/g in patients that did not recur (P=0.02). Patients with low yeast concentrations in their stools (<104/g) recurred more often (14/15, 93%) compared with patients with higher levels (19/35, 54%, P=0.007). Clearance of S. boulardii was rapid; only 4% had positive stools 3 days after stopping dosing. After chronic dosing of S. boulardii, patients with low stool concentrations had a higher likelihood of recurrence of CDD. Stool concentrations were also lower during periods of diarrhoea. These results show the importance of characterizing the dynamics of a therapeutic microorganism in patients with disease, as kinetic studies in healthy volunteers may not give a true reflection of the disturbed microecology in the disease state.
Article
Small-bowel resection in animals results in alterations of the morphology and functional adaptation in the remaining intestine. The aim of our study was to study the effect of Saccharomyces boulardii versus placebo in rats after 50% small-bowel resection. Sixty-three rats were assigned to one of three groups: small-bowel resection (n = 31), transected surgery controls (n = 16), or non-surgical controls (n = 16). Of the 31 rats with small-bowel resection, 15 were given S. boulardii (140 mg/dl), and 16 were given placebo. Intestinal markers measured included bacterial overgrowth (BO) on days 4 and 8 and translocation into mesenteric lymph nodes, liver, and spleen. Markers of small-bowel adaptation included histomorphology of the mucosa, protein content, and various brush-border enzymes (sucrase, glucoamylase, n-aminopeptidase). In the jejunal mucosal samples on day 8, S. boulardii-treated rats showed a significant increase in protein content (58.3 +/- 12 mg/10 cm) compared with placebo-treated rats (29.2 +/- 1.8) or non-surgery controls (18.3 +/- 1.2; P < 0.001). S. boulardii-treated rats also had significantly higher levels of all three brush-border enzymes. A significant increase of enzyme-specific activities was observed in the ileum of S. boulardii resected rats compared with the placebo resected group on day 4, and no significant differences were seen in the remnant ileum except an increase in protein content in S. boulardii-treated rats on day 8. Histomorphometric studies showed no differences in ileal villus height or translocation frequencies by day 8 in S. boulardii or placebo resected rats. These data indicate that, after resection, S. boulardii does not modify bacterial overgrowth or translocation frequency but does significantly enhance the functional adaptation of the remaining intestinal segments.