Article

Gastroprotective Effect of Saccharomyces boulardii in a Rat Model of Ibuprofen-Induced Gastric Ulcer

February 2010
Pharmacology 85(3):188-93

DOI:10.1159/000275146

Source
PubMed

Authors:

Philippe Girard

Biocodex

Yannick Pansart

Biocodex

Saccharomyces boulardii is a probiotic yeast which has been shown to protect the gastrointestinal microflora from disequilibrium and from associated gastrointestinal disorders. However, no study has explored the potential effect of this probiotic in ulcer models. The present study was designed to address this goal using the ibuprofen-induced ulcer rat model. Oral administration of ibuprofen (100 mg/kg) for 6 consecutive days induced ulceration of the gastric mucosa. Oral co-administration of S. boulardii (Biocodex, France) at 1.2, 4 or 12 x 10(10) CFU/kg dose-dependently and significantly reduced the numbers of gastric ulcers and the ulceration surface of the gastric mucosa. At the same time, serum nitrate and nitrite levels were measured before and on the 6th day. Contrary to what we expected, the serum nitrate and nitrite levels did not increase after ibuprofen administration, but this parameter significantly augmented in the groups where ibuprofen was co-administered with the two highest doses of S. boulardii. The present findings suggest that S. boulardii offers some potential in the treatment or prevention of ulcers induced by non-steroidal anti-inflammatory drugs, but its mechanism of action needs to be further explored.

Probiotics as a Therapeutic Approach for Non-infectious Gastric Ulcer Management: a Comprehensive Review

Article

Full-text available

Aug 2024

A gastric ulcer is a stomach lining or nearby intestine disruption caused by acid and pepsin. Helicobacter pylori (H. pylori) and NSAIDs are the primary culprits behind stomach infections that can lead to gastric ulcers and other digestive disorders. Additionally, lifestyle choices such as alcohol consumption and cigarette smoking, stress, and exposure to cold environments can also contribute to non-infectious gastric ulcers. Various treatments are available for gastric ulcers, including antibiotics, anticholinergics, and antacids. However, potential concerns include antibiotic resistance, side effects, and treatment failure. Considering this, there is a need for an alternative approach to manage it. Fortunately, probiotics, typically Lactobacillus and Bifidobacterium, show potential for healing gastric ulcers, offering a non-invasive alternative to conventional treatments. A notable concern arises from applying probiotic bacteria stemming from the propensity of pathogenic bacteria to develop antimicrobial resistance in response to antibiotic therapies. Therefore, the use of yeast becomes more imperative due to its natural resistance to antibacterial antibiotics for antibacterial-treated patients. Probiotic bacteria and yeasts could heal gastric ulcers by regulating the immune response, reducing inflammation, and restoring the balance between defensive and aggressive factors of the gastric layer. This comprehensive review provides an in-depth analysis of the benefits of probiotics and their potential as a therapeutic treatment for non-infectious gastric ulcers, along with other probiotic options. In particular, this review provides a succinct summary of multiple literature studies on probiotics, emphasising the distinctive properties of yeast probiotics, as well as their (bacteria and yeasts) application in the management of non-infectious gastric ulcers.

Prophylactic Effect and Antiulcerogenic Potential of Probiotic Lactiplantibacillus plantarum E1K2R2 and its Exopolysaccharide Against Ibuprofen-Induced Acute Gastric Ulcer

Article

Full-text available

Jul 2024

Lactiplantibacillus plantarum (Lpb. plantarum), as a safe probiotic microorganism, has been documented for its production of multiple bioactive compounds, such as exopolysaccharides (EPS), which have been used in the treatment of many gastrointestinal diseases, including gastric ulcers. The present study aims to investigate the prophylactic and antiulcerogenic effects of the potential probiotic Lbp. plantarum E1K2R2 and its EPS against ibuprofen-induced gastric ulcer. A gastric ulcer model was established by feeding fasted rats with ibuprofen at a single dose (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (10⁹ CFU), its EPS (200 mg/kg bw), and the anti-ulcer reference drug (omeprazole) (20 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. The mechanisms were meticulously examined, focusing on the anti-secretory activity and mucus production as well as the anti-inflammatory and antioxidant activities. The findings revealed that the gastro-preventive effect of Lbp. plantarum E1K2R2 (88.43%) was higher than that of the EPS (66.26%) and close to that of omeprazole (89.87%). This effect was achieved through similar mechanisms, including regulation of the secretory activity, augmentation of mucus production, mitigation of inflammation, and enhancement of the gastric mucosa’s antioxidant capacity. Moreover, it was found that Lbp. plantarum E1K2R2 and its EPS induce the activities of gastric antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and S-transferase (GST); enhance glutathione (GSH) content; and reduce mucosal nitric oxide (NO), myeloperoxidase (MPO), and malondialdehyde (MDA) levels. Furthermore, histopathological and hematological examinations confirmed that both pre-treatments could effectively maintain the structural integrity of the gastric mucosa and improve some hematological parameters, respectively. This implies that Lpb. plantarum E1K2R2 and its EPS possess the potential to counteract ibuprofen-associated gastric ulcers, leveraging a variety of protective mechanisms.

Potential role of probiotics in the management of gastric ulcer (Review)

Article

Full-text available

Apr 2016

Gastric ulcer is one of the most common chronic gastrointestinal diseases characterized by a significant defect in the mucosal barrier. Helicobacter pylori (H. pylori) infection and the frequent long‑term use of non‑steroidal anti‑inflam-matory drugs are major factors involved in gastric ulcer development. Acid inhibitors and antibiotics are commonly used to treat gastric ulcer. However, in the last few decades, the accumulating evidence for resistance to antibiotics and the side effects of antibiotics and acid inhibitors have drawn attention to the possible use of probiotics in the prevention and treatment of gastric ulcer. Probiotics are live microorganisms that when administered in adequate amounts confer health benefits on the host. Currently, the available experimental and clinical studies indicate that probiotics are promising for future applications in the management of gastric ulcers. This review aims to provide an overview of the general health benefits of probiotics on various systemic and gastrointestinal disorders with a special focus on gastric ulcer and the involved cellular and molecular mechanisms: i) Protection of gastric mucosal barrier; ii) upregulation of prostaglandins, mucus, growth factors and anti‑inflammatory cytokines; iii) increased cell proliferation to apoptosis ratio; and iv) induction of angio-genesis. Finally, some of the available data on the possible use of probiotics in H. pylori eradication are discussed.

Probiotics maintain the gut microbiome homeostasis during Indian Antarctic expedition by ship. www.nature.com/scientificreports

Article

Sep 2021

Probiotic bacteria protect against indomethacin-induced gastric ulcers through modulation of oxidative stress, inflammation, and apoptosis

Article

Full-text available

May 2024
MOL BIOL REP

Background Indomethacin is an anti-inflammatory drug that causes ulcers on the gastric mucosa due to its use. Probiotic bacteria are live microorganisms, and it has been stated by various studies that these bacteria have antioxidant and anti-inflammatory effects. In this study, we investigated the possible protective effect of various types of probiotic bacteria (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against acute gastric mucosal damage caused by indomethacin. Methods Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5 mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100 mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1 ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100 mg/kg dose of indomethacin was given. After the application, the rats were anesthetized with ketamine xylazine, killed under appropriate conditions, the abdominal cavity was opened and the stomach tissues were removed. The obtained gastric tissues were used in the biochemical and histopathological analyses discussed below. All data were statistically evaluated by one-way ANOVA using SPSS 20.00, followed by Duncan Post hoc test. The data were expressed as mean ± SD. P < 0.05 was considered statistically significant. Results As a result, the administration of indomethacin caused gastric damage, stimulating oxidative stress, inflammation, and apoptosis. We found that the use of probiotic bacteria reduces oxidative stress (TOC), increases the activity of antioxidant enzymes (TAC), suppresses inflammation (IL-6 and Tnf-α), and inhibits apoptosis (Bax and Bcl-2) (P < 0.05). Conclusion Probiotic treatment can mitigate gastric damage and apoptosis caused by indomethacin-induced gastric damage in rats. Probiotic also enhances the restoration of biochemical oxidative enzymes as it has anti-inflammatory, antioxidant, and antiapoptotic properties.

Clinicopathologic and gastrointestinal effects of administration of prednisone, prednisone with omeprazole, or prednisone with probiotics to dogs: A double‐blind randomized trial

Article

Full-text available

Mar 2023
J VET INTERN MED

Background The efffect of administering of probiotics or twice‐daily omeprazole on glucocorticoid‐induced gastric bleeding in dogs is unknown. Hypothesis Compare gastrointestinal bleeding among dogs administered placebo, prednisone (2 mg/kg q24h), prednisone with omeprazole (1 mg/kg q12h), or prednisone with probiotics (Visbiome, 11.2‐22.5 billion CFU/kg q24h) for 28 days. Animals Twenty‐four healthy research dogs. Methods Double‐blinded, placebo‐controlled randomized trial. Clinical signs and endoscopic gastrointestinal mucosal lesion scores at baseline (t1), day 14 (t2), and day 28 (t3) were compared using split‐plot repeated‐measures mixed‐model ANOVAs. Results Fecal score differed by treatment‐by‐time (F[6,40] = 2.65, P < .03), with higher scores in groups receiving prednisone at t3 than t1. Nineteen of thirty‐three episodes of diarrhea occurred in the prednisone with omeprazole group. Gastric mucosal lesion scores differed by treatment‐by‐time (F[6,60] = 2.86, P = .05), among treatment groups (F[3,60] = 4.9, P = .004), and over time (F[2,60] = 16.5, P < .001). Post hoc analysis revealed lesion scores increased over time for all groups receiving prednisone. At t3, scores for the prednisone (8.7 ± 4.9) and prednisone with probiotics (8.7 ± 4.9) groups differed significantly from placebo (1.8 ± 1.8; P ≤ .04), whereas scores for the prednisone with omeprazole (6.5 ± 5.5) group did not differ from placebo (P = .7). Ulcers occurred only in dogs receiving prednisone. Conclusions and Clinical Importance Prednisone‐induced gastric bleeding. Co‐administration of omeprazole partially mitigated bleeding, but a similar protective benefit was not demonstrated by co‐administration of the evaluated probiotic.

Role of Gastric Microorganisms Other than Helicobacter pylori in the Development and Treatment of Gastric Diseases

Article

Full-text available

Mar 2022
BMRI

The microenvironment in the stomach is different from other digestive tracts, mainly because of the secretion of gastric acid and digestive enzymes, bile reflux, special mucus barrier, gastric peristalsis, and so on, which all contribute to the formation of antibacterial environment. Microecological disorders can lead to gastric immune disorders or lead to the decrease of dominant bacteria and the increase of the abundance and virulence of pathogenic microorganisms and then promote the occurrence of diseases. The body performs its immune function through innate and adaptive immunity and maintains microbial balance through the mechanism of immune homeostasis. Microecological imbalance can lead to the invasion of pathogenic microorganisms and damage mucosal barrier and immune system. The coexistence of gastric microorganisms (including viruses and fungi) may play a synergistic or antagonistic role in the pathogenesis of gastric diseases. Probiotics have the ability to compete with intestinal pathogens, increase the secretion of immunoglobulin A (IgA), stimulate the production of mucin, bacteriocin, and lactic acid, regulate the expression and secretion of cytokines, and regulate the growth of microbiota, which all have beneficial effects on the host microbial environment. At present, most studies focused on Helicobacter pylori, ignoring other stomach microbes and the overall stomach microecology. So, in this article, we reviewed advances in human gastric microecology, the relationship between gastric microecology and immunity or gastric diseases, and the treatment of probiotics in gastric diseases, in order to explore new area for further study of gastric microorganisms and treatment of gastric diseases.

Probiotics maintain the gut microbiome homeostasis during Indian Antarctic expedition by ship

Article

Full-text available

Sep 2021

Ship voyage to Antarctica is a stressful journey for expedition members. The response of human gut microbiota to ship voyage and a feasible approach to maintain gut health, is still unexplored. The present findings describe a 24-day long longitudinal study involving 19 members from 38th Indian Antarctic Expedition, to investigate the impact of ship voyage and effect of probiotic intervention on gut microbiota. Fecal samples collected on day 0 as baseline and at the end of ship voyage (day 24), were analyzed using whole genome shotgun sequencing. Probiotic intervention reduced the sea sickness by 10% compared to 44% in placebo group. The gut microbiome in placebo group members on day 0 and day 24, indicated significant alteration compared to a marginal change in the microbial composition in probiotic group. Functional analysis revealed significant alterations in carbohydrate and amino acid metabolism. Carbohydrate-active enzymes analysis represented functional genes involved in glycoside hydrolases, glycosyltransferases and carbohydrate binding modules, for maintaining gut microbiome homeostasis. Suggesting thereby the possible mechanism of probiotic in stabilizing and restoring gut microflora during stressful ship journey. The present study is first of its kind, providing a feasible approach for protecting gut health during Antarctic expedition involving ship voyage.

Potential of probiotics for use as functional foods in patients with non-infectious gastric ulcer

Article

Mar 2021
TRENDS FOOD SCI TECH

Background Non-infectious gastric ulcer is one of the most common diseases resulting from improper eating habits, alcoholism, and excessive mental stress. It is more common than infected gastric ulcer, which is caused by Helicobacter pylori. Probiotics have been widely used as functional foods to protect human health and treat diseases of the digestive system. Many studies have examined the therapeutic effects of probiotics on the gastric ulcers caused by H. pylori infection. In contrast, few studies and clinical cases are available on the application of probiotics in the therapeutic treatment of non-infectious gastric ulcer. Scope and approach The current causes and mechanisms of non-infectious gastric ulcers were analyzed, and current drugs and potential therapeutic substances for the treatment of non-infectious gastric ulcer were evaluated. Compared with chemical medicines and other therapies, probiotics feature many advantages and have great potential to be used for the treatment of non-infectious gastric ulcer. To comprehensively assess the potential of probiotics to be used for the treatment of non-infectious gastric ulcer, we analyzed current studies relating to the pathogenesis, theoretical basis, examples, and mechanism of probiotics for treating non-infectious gastric ulcer, as well as effective delivery systems for probiotics. The goal of this review was to provide insight into the potential of probiotics to treat non-infectious gastric ulcers and the mechanisms underlying their efficacy. Key findings and conclusions In addition to smoking, alcohol abuse and excessive mental stress, the lack of essential elements in the body, and microfloral imbalances have been shown to be major causes of non-infectious gastric ulcer. In light of the side effects and limitations of currently used drugs, probiotic therapy has proven to be the most effective treatment. A theoretical analysis and recent findings suggest that probiotics provide numerous advantages and have great potential for treating non-infectious gastric ulcer for their ability to inhibit pathogenic intestinal bacteria, promote anti-inflammatory activity, heal gastric mucosal injury, and stimulate the immune system. The molecular mechanism of probiotics in the treatment of non-infectious gastric ulcers was analyzed. TRPV1 (transient receptor potential vanilloid 1) was proposed as a possible candidate target for the therapeutic effects of probiotics on non-infectious gastric ulcer.

1H-NMR metabolomics response to a realistic diet contamination with the mycotoxin deoxynivalenol: Effect of probiotics supplementation

Article

Full-text available

Mar 2020
FOOD CHEM TOXICOL

Low-level contamination of food and feed by deoxynivalenol (DON) is unavoidable. We investigated the effects of subclinical treatment with DON, and supplementation with probiotic yeast Saccharomyces cerevisiae boulardii I1079 as a preventive strategy in piglets. Thirty-six animals were randomly assigned to either a control diet, a diet contaminated with DON (3 mg/kg), a diet supplemented with yeast (4 × 10⁹ CFU/kg), or a DON-contaminated diet supplemented with yeast, for four weeks. Plasma and tissue samples were collected for biochemical analysis, ¹H-NMR untargeted metabolomics, and histology. DON induced no significant modifications in biochemical parameters. However, lesion scores were higher and metabolomics highlighted alterations of amino acid and 2-oxocarboxylic acid metabolism. Administering yeast affected aminoacyl-tRNA synthesis and amino acid and glycerophospholipid metabolism. Yeast supplementation of piglets exposed to DON prevented histological alterations, and partial least square discriminant analysis emphasised similarity between the metabolic profiles of their plasma and that of the control group. The effect on liver metabolome remained marginal, indicating that the toxicity of the mycotoxin was not eliminated. These findings show that the ¹H-NMR metabolomics profile is a reliable biomarker to assess subclinical exposure to DON, and that supplementation with S. cerevisiae boulardii increases the resilience of piglets to this mycotoxin.

Probiyotikler ve Yara İyileşme Sürecine Etkileri: Anjiyogenez Üzerine Etki Mekanizması

Article

Full-text available

Dec 2018

Probiyotikler, gastrointestinal sistem hastalıklarından depresyona kadar çok sayıda hastalık grubunda çalışılmış ve bu hastalıklar üzerinde probiyotiklerin olumlu etkiler gösterebildiği bildirilmiştir. Probiyotiklerin bildirilen olumlu etkilerini, hastalık gelişimi ve tedavi sürecinde canlı mikrobiyotasını zenginleştirerek gerçekleştirdiği düşünülmektedir. Yara iyileşmesi ise birçok farklı mekanizmanın etkisi altında bulunan bir süreçtir. Bakterilerin bu süreçte faydalı etkileri olduğu gibi farklı bakteri türlerine bağlı olarak olumsuz etkileri de olabilmektedir. Son yapılan çalışmalarda bazı probiyotik bakteri türlerinin topikal uygulaması ya da sistemik etkileri ile yara iyileşmesi üzerine etkili olduğu saptanmıştır. Özellikle gastrik ülserler üzerinde yapılan çalışmalarda probiyotik bakterilerin antibiyotikler ile karşılaştırıldığında, antibiyotik direncinin olduğu durumlarda anjiyogenezanjiyogenez üzerinden etki ederek daha etkili sonuçlar gösterdiği belirtilmiştir. Probiyotiklerin etki mekanizmaları ve hangi bakteri türlerinin etkin olduğuna dair daha fazla çalışma yapılması gerekmektedir.

A Mutation in PGM2 Causing Inefficient Galactose Metabolism in the Probiotic Yeast Saccharomyces boulardii

Article

Full-text available

May 2018
APPL ENVIRON MICROB

The probiotic yeast Saccharomyces boulardii has been extensively studied for preventing and treating diarrheal diseases and is now commercially available in some countries. S. boulardii displays notable phenotypes, such as high optimal growth temperature, high tolerance against acidic conditions, and the inability to form ascospores, which differentiate S. boulardii from S. cerevisiae. The majority of prior studies stated that S. boulardii exhibits sluggish or halted galactose utilization. Nonetheless, molecular mechanisms underlying inefficient galactose uptake have yet to be elucidated. When galactose utilization of a widely-used S. boulardii strain, ATCC MYA-796, was examined under various culture conditions, the S. boulardii strain could consume galactose but at a much slower rate than S. cerevisiae. While S. boulardii had all GAL genes in the genome through the analysis of genomic sequencing data according to a previous study, a point mutation (G1278A) in PGM2 coding for phosphoglucomutase was identified in the genome of the S. boulardii strain. As the point mutation resulted in truncation of Pgm2 which is known to play a pivotal role in galactose utilization, we hypothesized that the truncated Pgm2 might be associated with inefficient galactose metabolism. Indeed, complementation of S. cerevisiae PGM2 in S. boulardii rescued galactose utilization. After reverting the point mutation into a full-length PGM2 in S. boulardii by Cas9-based genome editing, the growth rates of wild type (with a truncated PGM2) and mutant (with a full-length PGM2) strains on glucose and galactose conditions were examined. As expected, the mutant (with a full-length PGM2) was able to ferment galactose faster than the wild type strain. Interestingly, the mutant showed a slower growth rate than the wild type strain on glucose at 37 °C. Also, the wild type strain was enriched in the mixed culture of the wild type and mutant strains on glucose at 37 °C, suggesting that the truncated PGM2 might offer better growth on glucose at a higher temperature in return for inefficient galactose utilization. Our results suggest that the point mutation in PGM2 might be involved in multiple phenotypes with diverging effects. IMPORTANCE Saccharomyces boulardii is a probiotic yeast strain capable of preventing and treating diarrheal diseases. However, genetics and metabolism of this yeast are largely unexplored. Especially, molecular mechanisms underlying inefficient galactose metabolism of S. boulardii remain unknown. Our study reports that a point mutation in PGM2 coding for phosphoglucomutase is responsible for inferior galactose utilization by S. boulardii. After correction of the mutated PGM2 via genome editing, the resulting strain was able to use galactose faster than a parental strain. While the PGM2 mutation made the yeast use galactose slowly, investigation of the genomic sequencing data of other S. boulardii strains revealed that the PGM2 mutation is evolutionarily conserved. Interestingly, the PGM2 mutation was beneficial for growth at a higher temperature on glucose. We speculate that the PGM2 mutation was enriched due to the selection in the natural habitat (sugar-rich fruits in tropical areas) of S. boulardii.

Probiotic Bacteria Bacillus Licheniformis Attenuates Gastric Ulcer Healing and Antagonizes the Ulcer Healing Effect of Ranitidine in Rats

Article

Full-text available

Jan 2015

Bacillus licheniformis is widely used as probiotic. It is reported to potentiate the effect of conventional antiulcer therapy in humans. The effect of Bacillus licheniformis on gastric ulcer healing and its interaction with ranitidine, a known antiulcer drug, was studied using acetic acid induced chronic gastric ulcer model in rats. The bacteria was administered orally at two different doses of 106 cells/kg and 103 cells/kg while ranitidine was given at a dose of 50 mg/kg. Bacillus licheniformis attenuated the ulcer healing in rats. It increased the ulcer score and ulcer index compared to vehicle treated animals. Histological studies of the ulcerated tissues supported the macroscopic findings. As expected, ranitidine increased gastric ulcer healing while the combination of ranitidine and Bacillus licheniformis showed decreased ulcer healing compared to ranitidine alone. It was concluded that Bacillus licheniformis aggravates gastric ulcer and antagonizes the effect of ranitidine on ulcer healing in rats.

Wu-Tou Decoction Inhibits Chronic Inflammatory Pain in Mice: Participation of TRPV1 and TRPA1 Ion Channels

Article

Full-text available

Mar 2015
BMRI

Wu-tou decoction (WTD) is a classic traditional Chinese medicine formula and has been used effectively to treat joint diseases clinically. Previous reports indicated that WTD possesses anti-inflammatory activity; however, its actions on pain have not been clarified. Here, we investigated the antinociceptive activity of WTD in CFA-induced mice, and its possible mechanism of the action associated with transient receptor potential (TRP) ion channels was also explored. Our results showed that 1.58, 3.15, and 6.30 g/kg WTD significantly attenuated mechanical, cold, and heat hypersensitivities. Moreover, WTD effectively inhibited spontaneous nociceptive responses to intraplantar injections of capsaicin and cinnamaldehyde, respectively. WTD also effectively suppressed jumping and wet-dog-shake behaviors to intraperitoneal injection of icilin. Additionally, WTD significantly reduced protein expression of TRPV1 and TRPA1 in dorsal root ganglia and skins of injured paw. Collectively, our data demonstrate firstly that WTD exerts antinociceptive activity in inflammatory conditions by attenuating mechanical, cold, and heat hypersensitivities. This antinociceptive effect may result in part from inhibiting the activities of TRPV1, TRPA1, and TRPM8, and the suppression of TRPV1 and TRPA1 protein by WTD was also highly effective. These findings suggest that WTD might be an attractive and suitable therapeutic agent for the management of chronic inflammatory pain.

Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice

Article

Feb 2014
BRIT J NUTR

Intestinal mucositis is an important toxic side effect of 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii is known to protect from intestinal injury via an effect on the gastrointestinal microbiota. The objective of the present study was to evaluate the effect of S. boulardii on intestinal mucositis induced by 5-FU in a murine model. Mice were divided into saline, saline (control)+5-FU or 5-FU+S. boulardii (16 × 109 colony-forming units/kg) treatment groups, and the jejunum and ileum were removed after killing of mice for the evaluation of histopathology, myeloperoxidase (MPO) activity, and non-protein sulfhydryl group (mainly reduced glutathione; GSH), nitrite and cytokine concentrations. To determine gastric emptying, phenol red was administered orally, mice were killed 20 min after administration, and the absorbance of samples collected from the mice was measured by spectrophotometry. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following oral administration. S. boulardii significantly reversed the histopathological changes in intestinal mucositis induced by 5-FU and reduced the inflammatory parameters: neutrophil infiltration (control 1·73 (sem 0·37) ultrastructural MPO (UMPO)/mg, 5-FU 7·37 (sem 1·77) UMPO/mg and 5-FU+S. boulardii 4·15 (sem 0·73) UMPO/mg); nitrite concentration (control 37·00 (sem 2·39) μm, 5-FU 59·04 (sem 11·41) μm and 5-FU+S. boulardii 37·90 (sem 5·78) μm); GSH concentration (control 477·60 (sem 25·25) μg/mg, 5-FU 270·90 (sem 38·50) μg/mg and 5-FU+S. boulardii 514·00 (sem 38·64) μg/mg). Treatment with S. Boulardii significantly reduced the concentrations of TNF-α and IL-1β by 48·92 and 32·21 % in the jejunum and 38·92 and 61·79 % in the ileum. In addition, S. boulardii decreased the concentrations of chemokine (C-X-C motif) ligand 1 by 5-fold in the jejunum and 3-fold in the ileum. Interestingly, S. boulardii reduced the delay in gastric emptying (control 25·21 (sem 2·55) %, 5-FU 54·91 (sem 3·43) % and 5-FU+S. boulardii 31·38 (sem 2·80) %) and induced the recovery of intestinal permeability (lactulose:mannitol ratio: control 0·52 (sem 0·03), 5-FU 1·38 (sem 0·24) and 5-FU+S. boulardii 0·62 (sem 0·03)). In conclusion, S. boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in intestinal mucositis induced by 5-FU.

The Probiotic Mixture VSL#3 Accelerates Gastric Ulcer Healing by Stimulating Vascular Endothelial Growth Factor

Article

Full-text available

Mar 2013
PLOS ONE

Studies assessing the effect and mechanism of probiotics on diseases of the upper gastrointestinal tract (GI) including gastric ulcers are limited despite extensive work and promising results of this therapeutic option for other GI diseases. In this study, we investigated the mechanisms by which the probiotic mixture VSL#3 (a mixture of eight probiotic bacteria including Lactobacilli, Bifidobacteria and Streptococcus species) heals acetic acid induced gastric ulcer in rats. VSL#3 was administered orally at low (6×109 bacteria) or high (1.2×1010 bacteria) dosages from day 3 after ulcer induction for 14 consecutive days. VSL#3 treatments significantly enhanced gastric ulcer healing in a dose-dependent manner. To assess the mechanism(s) whereby VSL#3 exerted its protective effects, we quantified the gene expression of several pro-inflammatory cytokines, protein and expression of stomach mucin-Muc5ac, regulatory cytokine-IL-10, COX-2 and various growth factors. Of all the components examined, only expression and protein production of VEGF was increased 332-fold on day 7 in the ulcerated tissues of animals treated with VSL#3. Predictably, animals treated with VEGF neutralizing antibody significantly delayed gastric ulcer healing in VSL#3 treated animals. This is the first report to demonstrate high efficacy of the probiotic mixture VSL#3 in enhancing gastric ulcer healing. Probiotic efficacy was effective at higher concentrations of VSL#3 by specifically increasing the expression and production of angiogenesis promoting growth factors, primarily VEGF.

Development of a High-Cell-Density Production Process for a Biotherapeutic Yeast, Saccharomyces cerevisiae var. boulardii, for Use as a Human Probiotic

Article

Apr 2025

Saccharomyces cerevisiae var. boulardii is a probiotic yeast widely recognized for its ability to enhance gut health and modulate a host’s microbiome. However, there are limited data on its large-scale cultivation in stirred tank bioreactors and subsequent downstream processing into a functional probiotic product. Different recipe formulations were evaluated and the recipe with the highest biomass yield and lowest process time was selected. Once the optimised batch was validated in the replicate batches, the statistical analysis indicated a high level of reproducibility, with low variability across key performance indicators such as biomass concentration (unit), CFU production (CFU.mL−1), and substrate utilization efficiency (g.g−1). The mean growth age in the bioreactor was 25.33 ± 1.16 h, with a CV of 4.56%, indicating minimal deviation between batches. Similarly, the final viable concentration exhibited a mean of 1.46 × 108 CFU.mL−1 with a CV of 11.68%, remaining within an acceptable range for biological processes, while the final biomass concentration had the lowest variability (CV of 3.94%) and a 95% CI of 12.134–13.266 g.L−1, highlighting the accuracy and consistency of the process. Productivity indicators, including cell productivity (growth time—biomass) and YPP (biomass), maintained low CV values (3.933% and 3.389%, respectively), reinforcing process efficiency and stability. The overlapping 95% confidence intervals across batches further confirmed that no statistically significant deviations existed, ensuring minimal batch-to-batch variability, and validating the scalability and robustness of the fermentation process. These findings provide strong evidence for the feasibility of large-scale probiotic yeast production that meets industrial production standards. The final freeze-dried product retained an 81% viability post-exposure to simulated gastrointestinal conditions, meeting WHO probiotic viability standards. These findings establish a scalable, optimized process for probiotic yeast production, with potential applications in biopharmaceutical manufacturing and functional food development, as confirmed by the techno-economic evaluations performed using SuperPro Designer®.

Pretreatment with water kefir reduces the development of acidified ethanol-induced gastric ulcers

Article

Full-text available

Sep 2022

To evaluate the gastroprotective and antioxidant effects of pretreatment with water kefir on ulcers induced with HCl/ethanol. All pretreatments lasted 14 days. Male mice were separated into five groups: the control (C) group received vehicle without ulcer induction; the ulcerated (U) group received vehicle; the lansoprazole (L) group received 30 mg/kg/day lansoprazole; the water kefir (WK15 and WK30) groups received WK at a dose of 0.15 or 0.30 ml/kg/day, respectively. Gastroprotection was measured by ulcer area, ulcer index and ulcer reduction percentage. Antioxidant effects were quantified by measuring advanced oxidized protein products (AOPPs), superoxide dismutase (SOD), and catalase activity in the stomach. Pretreatment with WK at both doses promoted gastroprotection against HCl/ethanol-induced ulcers much like the pretreatment with lansoprazole. In addition, WK decreased protein oxidation while increasing SOD and catalase activity. We concluded that pretreatment with water kefir increases the activity of antioxidant enzymes, preventing gastric lesions induced by HCl/ethanol by maintaining the antioxidant performance in gastric tissue.

Role of Probiotics in Prophylaxis of Helicobacter Pylori Infection

Article

Feb 2019

Helicobacter pylori, a pathogenic bacterium, has been known to be the root cause of numerous gastrointestinal disorders. In patients showing symptoms of its infection, antibiotic therapy is a likely treatment. However, the high cost of antibiotic therapy, associated antibiotic resistance along with other adverse effects has led to the use of probiotics for Helicobacter pylori treatment. In recent times, probiotics have played an essential role as complementary prophylaxis for gastrointestinal diseases, thus minimizing antibiotics' usage and their side effects. Probiotics are live microbial agents that exude beneficial effects on their hosts when administered in the proper dosage. The growth of the organism has been reported to be inhibited to a great extent by probiotics and research employing animal models has shown a significant reduction in H. pylori-associated gastric inflammation. In human clinical trials, it has been observed that treatment with probiotics alleviated gastritis symptoms caused by H. pylori and reduced colonization of the organism. As expected, complete eradication of H. pylori infection has not yet been reported by the administration of probiotics alone. Complement treatments using probiotics have shown to benefit infected individuals by decreasing the harmful effects of H. pylori eradication treatment using antibiotics. Long-term administration of probiotics might have favourable outcomes in H. pylori infection especially by decreasing the risk of development of diseases caused by increased levels of gastric inflammation. One such chronic condition is gastric ulcer which occurs due to considerable damage to the mucosal barrier by H. pylori colonization. This review provides a brief description of the promising role of probiotics as a complementary treatment to control H. pylori infection and consequently the management of various gastrointestinal disorders among populations with a special focus on gastric ulcer.

Anti-Hypercholesterolemic Effect of Saccharomyces boulardii in the Hamster

Article

Nov 2014

Background/aims: Hypercholesterolemia is a major risk factor for coronary artery disease and probiotics have been suggested as tools to manage elevated cholesterol levels. Methods: The present study investigated the ability of the biotherapeutic agent Saccharomyces boulardii (Sb-Biocodex) to reduce the hypercholesterolemia induced by a 0.1% cholesterol-enriched diet in the hamster. Results: In a first experiment, chronic oral treatment with S. boulardii at 12 × 10(10) CFU/kg (3 g/kg) twice a day was started from the beginning of the cholesterol diet and continued for 14 days ('preventive protocol'). In the second experiment, S. boulardii was given 14 days after the beginning of the cholesterol diet when hypercholesterolemia had developed and continued for an additional 14 days ('curative protocol'). In the preventive protocol, administration of the yeast significantly reduced hypercholesterolemia (14%) induced by the cholesterol-enriched diet compared to the group receiving only the cholesterol diet. In the curative protocol, S. boulardii significantly reduced hypercholesterolemia (12%) induced by the cholesterol-enriched diet, too. Moreover, the yeast significantly decreased the serum triglyceride increase by 39%. Conclusion: S. boulardii possesses anti-hypercholesterolemic properties in the hamster worthy of further evaluation in clinical studies.

Saccharomyces boulardii'. A Review of an Innovative Biotherapeutic Agent

Article

Full-text available

Sep 1993
Microb Ecol Health Dis

Saccharomyces boulardii is a non-pathogenic yeast which has been used as both a preventive and therapeutic agent for the treatment of a variety of diarrhoeal diseases. The studies with animal models and evidence from human volunteers and patients indicate a profile which is effective in the therapy of diarrhoea and is remarkably safe for oral ingestion. The pharmacokinetic data demonstrate that 5. boulardü reaches a steady-state concentration quickly and maintains a high stable level as long as the yeast is taken daily. Once the agent is discontinued, S. boulardü is quickly eliminated from the colon. Clinical trials studying antibiotic-associated diarrhoea, nasogastric-tube alimentation diarrhoea, Clostridium difficile-disease, acute diarrhoea and chronic diarrhoea in HI V-infected patients are reviewed.

Saccharomyces boulardii in childhood

Article

Full-text available

Mar 2009
Eur J Pediatr

Introduction Probiotics are live microorganisms which confer a health benefit on the host. Saccharomyces boulardii, a yeast, has been found to be an effective probiotic in double-blind placebo-controlled randomized clinical studies. Materials and methods We reviewed the established mechanisms of actions and clinical efficacy in children of S. boulardii. Conclusions The mechanisms of action of S. boulardii depend mainly on the inhibition of some bacterial toxins, anti-inflammatory effects, and on stimulating effects on the intestinal mucosa such as trophic effects on the brush border enzymes and immunostimulatory effects. At present, in pediatric populations, there is evidence that S. boulardii is beneficial for the treatment of acute gastroenteritis and the prevention of antibiotic-associated diarrhea. More data are needed in other indications such as traveller’s diarrhea, Helicobacter pylori eradication, and inflammatory bowel disease. S. boulardii is a yeast strain that has been extensively studied in vitro and in vivo. Recent data have opened the door for new therapeutic indications.

Saccharomyces boulardii effects on gastrointestinal diseases

Article

Full-text available

Oct 2008

Health benefits attributed to probiotics have been described for decades. They include the treatment and the prevention of gastrointestinal diseases, vaginal and urinary infections and allergies. Saccharomyces boulardii, a species of yeast widely distributed, has been described as a biotherapeutic agent since several clinical trials displayed its beneficial effects in the prevention and the treatment of intestinal infections and in the maintenance of inflammatory bowel disease. All these diseases are characterized by acute diarrhoea. Administration of the yeast in combination or not with an antibiotherapy has shown to decrease significantly the duration and the frequency of diarrhoea. Experimental studies elucidated partially the molecular mechanisms triggered to improve the host health. The discovery of its anti-inflammatory and immuno-modulatory activities in correlation with the advances in the understanding of mucosal immunology opens a new field of perspectives in S. boulardii therapeutic applications.

Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum

Article

Full-text available

Dec 1996

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.

The Search for a Better Treatment for Recurrent Clostridium difficile Disease: Use of High‐Dose Vancomycin Combined with Saccharomyces boulardii

Article

Full-text available

Nov 2000

Recurrent Clostridium difficile disease (CDD) is a difficult clinical problem because antibiotic therapy often does not prevent further recurrences. In a previous study, the biotherapeutic agent Saccharomyces boulardii was used in combination with standard antibiotics and was found to be effective in reducing subsequent recurrences of CDD. In an effort to further refine a standard regimen, we tested patients receiving a regimen of a standard antibiotic for 10 days and then added either S. boulardii (1 g/day for 28 days) or placebo. A significant decrease in recurrences was observed only in patients treated with high-dose vancomycin (2 g/day) and S. boulardii (16.7%), compared with those who received high-dose vancomycin and placebo (50%; P = .05). No serious adverse reactions were observed in these patients. Comparison of data from this trial with data from previous studies indicates that recurrent CDD may respond to a short course of high-dose vancomycin or to longer courses of low-dose vancomycin when either is combined with S. boulardii.

Preclinical and Clinical Pharmacology of Biotherapeutic Agents: Saccharomyces boulardii

Article

Full-text available

Nov 2001

Probiotic agents are living microorganisms that, upon ingestion, exert health benefits beyond inherent general nutrition. In this context, we must differentiate between biotherapeutics as approved drugs and dietary supplements and food products containing probiotic bacteria that are not considered drugs. At present the only biotherapeutic agent which is prescribable in some European countries, indicated to relieve specific diseases, is the yeast Saccharomyces boulardii. In this review we consider the various preclinical and clinical aspects of biotherapeutics as basic drugs and the biotherapeutic powers of their use in the treatment of some surgical enteropathies.

Mechanisms by which endogenous glucocorticoid protects against indomethacin-induced gastric injury in rats

Article

Full-text available

Dec 2002

We investigated the mechanisms underlying the protective action of glucocorticoids against indomethacin-induced gastric lesions. One-week adrenalectomized rats with or without corticosterone replacement (4 mg/kg sc) were administered indomethacin (25 mg/kg sc), and gastric secretion (acid, pepsin, and mucus), motility, microvascular permeability, and blood glucose levels were examined. Indomethacin caused gastric lesions in sham-operated rats, with an increase in gastric motility and microvascular permeability as well as a decrease in mucus secretion. Adrenalectomy significantly worsened the lesions and potentiated these functional disorders. Glucose levels were lowered by indomethacin in sham-operated rats, and this response was enhanced by adrenalectomy. The changes observed in adrenalectomized rats were prevented by supplementations of corticosterone at a dose mimicking the indomethacin-induced rise in corticosterone, whereas the protective effect of corticosterone was attenuated by RU-38486, a glucocorticoid receptor antagonist. We conclude that the gastroprotective action of endogenous glucocorticoids may be provided by their support of glucose homeostasis and inhibitory effects on enhanced gastric motility and microvascular permeability as well as maintaining the production of mucus.

Dose–Response Relationship and Mechanism of Action of Saccharomyces boulardii in Castor Oil-Induced Diarrhea in Rats

Article

Full-text available

May 2003

For biotherapeutic agents, there is a lack of information on dose-response relationships and mechanism of action. The present study was designed to address these issues for Saccharomyces boulardii using the rat model of castor oil-induced diarrhea. A single dose of Saccharomyces boulardii at 12 x 10(10) CFU/kg of viable cells given 1 hr before castor oil administration significantly reduced the onset of diarrhea. Repeated ingestion of the yeast, twice daily between 1.2 and 12 x 10(10) CFU/kg for 5 days before castor oil, showed a dose-response relationship. The percentage of rats with diarrhea decreased and a stronger protection was afforded by the repeated treatment. The mechanism of action of Saccharomyces boulardii in this model was investigated with two classes of antagonists, naloxone and L-arginine. The effect of Saccharomyces boulardii was not inhibited by naloxone but was significantly reduced by L-arginine. This last result suggests a novel mechanism of action for Saccharomyces boulardii involving a possible inhibition of nitric oxide production by the yeast.

Saccharomyces boulardii Interferes with Enterohemorrhagic Escherichia coli-Induced Signaling Pathways in T84 Cells

Article

Full-text available

Feb 2003
INFECT IMMUN

Enterohemorrhagic Escherichia coli (EHEC) infections are associated with the modification of tight-junction permeability and synthesis of proinflammatory cytokine interleukin-8 (IL-8). In a previous study, it was demonstrated that EHEC-induced IL-8 secretion is due to the involvement of the mitogen-activated protein kinase (MAPK), AP-1, and NF-kappaB pathways. In this study, we investigated the effect of the yeast Saccharomyces boulardii on EHEC infection in T84 cells. For this purpose, cells were (i) incubated with bacteria and yeast at the same time or (ii) incubated overnight with yeast cells that were maintained during infection or eliminated by several washes before infection. Coincubation is sufficient to maintain the transmonolayer electrical resistance (TER) of EHEC-infected cells, whereas the preincubation of cells with the yeast without elimination of the yeast during infection is necessary to significantly decrease IL-8 secretion. We thus analyzed the mechanisms of S. boulardii action. We showed that S. boulardii has no effect on EHEC growth or on EHEC adhesion. Kinetics studies revealed that EHEC-induced myosin light chain (MLC) phosphorylation precedes the decrease of TER. ML-7, an MLC kinase inhibitor, abolishes the EHEC-induced MLC phosphorylation and decrease of TER. Studies show that S. boulardii also abolishes EHEC-induced MLC phosphorylation. We demonstrated that the preincubation of cells with S. boulardii without washes before EHEC infection inhibits NF-kappaB DNA binding activity, phosphorylation and degradation of IkappaB-alpha, and activation of the three members of a MAPK group (extracellular signal-regulated protein kinases 1 and 2, p38, and c-jun N-terminal kinase). These findings demonstrate that S. boulardii exerts a preventive effect on EHEC infection by (i) interfering with one of the transduction pathways implicated in the control of tight-junction structure and (ii) decreasing IL-8 proinflammatory secretion via inhibition of the NF-kappaB and MAPK signaling pathways in infected T84 cells.

Dual action of prostaglandin E-2 on gastric acid secretion through different EP-receptor subtypes in the rat

Article

Full-text available

Aug 2005

We examined the role of prostaglandin E (EP) receptor subtypes in the regulation of gastric acid secretion in the rat. Under urethane anesthesia, the stomach was superfused with saline, and the acid secretion was determined at pH 7.0 by adding 50 mM NaOH. The acid secretion was stimulated by intravenous infusion of histamine or pentagastrin. Various EP agonists were administered intravenously, whereas EP antagonists were given subcutaneously 30 min or intravenously 10 min before EP agonists. PGE(2) suppressed the acid secretion stimulated by either histamine or pentagastrin in a dose-dependent manner. The acid inhibitory effect of PGE(2) was mimicked by sulprostone (EP(1)/EP(3) agonist) but not butaprost (EP(2) agonist) or AE1-329 (EP(4) agonist). The inhibitory effect of sulprostone, which was not affected by ONO-8711 (EP(1) antagonist), was more potent against pentagastrin- (50% inhibition dose: 3.6 mug/kg) than histamine-stimulated acid secretion (50% inhibition dose: 18.0 mug/kg). Pentagastrin increased the luminal release of histamine, and this response was also inhibited by sulprostone. On the other hand, AE1-329 (EP(4) agonist) stimulated the acid secretion in vagotomized animals with a significant increase in luminal histamine. This effect of AE1-329 was totally abolished by cimetidine as well as AE3-208 (EP(4) antagonist). These results suggest that PGE(2) has a dual effect on acid secretion: inhibition mediated by EP(3) receptors and stimulation through EP(4) receptors. The former effect may be brought about by suppression at both parietal and enterochromaffin-like cells, whereas the latter effect may be mediated by histamine released from enterochromaffin-like cells.

Saccharomyces boulardii decreases inflammation and intestinal colonization by Candida albicans in a mouse model of chemically-induced colitis

Article

Full-text available

Dec 2007

The present study was designed to investigate the effects of Saccharomyces boulardii on inflammation and intestinal colonization by Candida albicans in a BALB/c mouse model of colitis that had been induced by dextran-sulfate-sodium (DSS). Colonization with C. albicans was established by oral gavage with a 200 microL suspension of 10(7) yeast cells. A 1.5% solution of DSS was administered in drinking water 1 h after C. albicans oral challenge, while 10(7) cells of S. boulardii was inoculated daily by oral gavage for 1 week. Faeces were collected daily for 2 weeks. Seven groups of mice consisting of those that were administered either C. albicans or S. boulardii or both were sacrificed after 14 days and samples of the colon were taken for histological scoring and real-time PCR (RT-PCR) analysis of inflammatory cytokines and toll-like receptors (TLRs). Compared to control animals that did not receive DSS, the number of C. albicans colonies recovered from faeces was significantly greater in mice receiving DSS. In contrast, the colony forming units (CFUs) of C. albicans were greatly reduced in mice receiving S. boulardii. The administration of this yeast decreased the severity of DSS-induced clinical scores and histological inflammation. At the mRNA expression level, an increase in TLR2 and TLR4 resulting from the presence of S. boulardii was associated with a reduction in the inflammatory cytokines TNFalpha and INFgamma. In mice receiving DSS and C. albicans, TLR4 was over-expressed by stimulation with both yeasts, but TLR2 and TNFalpha, which were increased by the administration of C. albicans alone, were decreased in the presence of S. boulardii. These results indicate that S. boulardii decreased inflammation and C. albicans colonization in this BALB/c mouse model of colitis.

Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCL, NaOH, hypertonic NaCL, and thermal injury

Article

Oct 1979
GASTROENTEROLOGY

Oral administration to fasted rats of either absolute ethanol, 0.6 N hydrochloric acid, 0.2 N sodium hydroxide, 25% sodium chloride, or boiling water produced extensive necrosis of the gastric mucosa. Pretreatment with several prostaglandins of the A, E, or F type, either orally or subcutaneously, prevented such necrosis, and the effect was dose-dependent. This property of prostaglandins is called "cytoprotection." The protective effect against oral administration of absolute ethanol was already maximal 1 min after PGE2 given orally, and 15-30 min after PGE2 given subcutaneously. Cytoprotection by prostaglandins is unrelated to the inhibition of gastric acid secretion since, (a) it is maximal at doses that have no effect on gastric secretion, and (b) anti-secretory compounds (cimetidine, methscopolamine bromide) and antacids are not cytoprotective. Although the mechanism of gastric cytoprotection is unknown, prostaglandins appear to increase the resistance of gastric mucosal cells to the necrotizing effect of strong irritants. These results suggest that certain prostaglandins, by a mechanism other than the inhibition of gastric acid secretion, maintain the cellular integrity of the gastric mucosa, and might be beneficial in the treatment of a variety of diseases in which gastric mucosal injury is present.

Moncada S, Palmer RMJ & Higgs EA.Nitric Oxide: Physiology, pathophysiology, and pharmacology. Pharm Rev 43: 109−142

Article

Jul 1991

Acid and Barriers: Current Research and Future Developments for Peptic Ulcer Therapy

Article

Feb 1990
Scand J Gastroenterol Suppl

Medical therapy for peptic ulcer disease has been targeted at inhibiting acid secretion based on the belief that ulcers occur due to an imbalance between aggressive and protective factors. New antisecretory agents are unlikely to show any dramatic improvement over the success and safety of histamine H2 receptor antagonists or the recently introduced H+K+ATPase proton pump antagonist omeprazole. The development of specific muscarinic M3 and gastrin receptor antagonists will provide useful agents to suppress acid and pepsinogen secretion by alternative means and may prevent the associated hypergastrinaemia seen with anti-secretory therapy. Enhancement of mucosal defence by site protective agents will be based on a better understanding of the vascular and immune factors involved in maintaining mucosal integrity and the growth factors that regulate wound healing. Molecular techniques are likely to produce the 'model anti-ulcer' agent which will effectively inhibit acid secretion and also enhance wound healing thus providing a cure for this chronic disease.

Endogenous prostaglandin: Its role in gastric mucosal blood flow and ethanol ulceration in rats

Article

Nov 1990
Prostag Other Lipid Mediat

The involvement of endogenous prostaglandins (PGs) in modulating gastric mucosal blood flow (GMBF) is still unclear. The present study was designed to demonstrate the role of this autacoid in the basal GMBF and the restoration of blood flow after restriction of blood supply to the stomach. The ex-vivo gastric chamber was prepared and the GMBF was measured by a laser Doppler technique. 20% ethanol incubation for 10 min in the chamber increased the basal GMBF and lessened the reduction of blood flow induced by absolute ethanol. It also decreased lesion formation caused by ethanol. Indomethacin 5 mg/kg, given s.c 60 min before experimentation had the opposite effects. Ligation of the gastric artery for 20 min which reduced the GMBF by 60%, worsened ethanol ulceration. There was a marked rebound of the GMBF after the ligation was released. Indomethacin totally abolished the blood flow rebound and aggravated ethanol ulceration. However, 20% ethanol incubation significantly potentiated such a rebound in blood flow and reduced lesion formation. Indomethacin pretreatment reversed these actions, whereas misoprostol administration produced the similar effects as 20% ethanol. It is concluded that GMBF plays an important role in ethanol ulceration and both basal and rebound GMBF is probably modulated by endogenous PGs.

Stimulation of IgA and secretory component of immunoglobulins in small intestine of rats treated with Saccharomyces boulardii

Article

Mar 1990

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)

Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: A prospective study

Article

May 1989
GASTROENTEROLOGY

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.

Prevention of clindamycin-induced mortality in hamster by Saccharomyces boulardii

Article

Nov 1984

Saccharomyces boulardii, a yeast used in a number of countries for general and antibiotic-associated gastrointestinal illnesses, was examined for possible application in the prevention of clindamycin-induced mortality in the hamster colitis model. Hamsters were given free access to an aqueous 5% suspension of lyophilized yeast for 3 days before and 10 days after administration of a single oral clindamycin dose of from 0.2 to 0.8 mg/kg. Mortality was recorded in groups of 7 to 20 animals every 24 h for 10 to 30 days. Mean cecal concentrations of S. boulardii were greater than 10(6) CFU/ml throughout the yeast administration period. Yeast treatment significantly decreased cumulative percent mortality by an average of 29%. Death onset was not affected by yeast treatment. Cecitis was present in 86% of moribund animals (N = 95) and was absent in all surviving animals examined (N = 27). Toxigenic Clostridium difficile was isolated from 13 of 14 moribund hamsters examined. No adverse effects of the yeast treatment were observed in animals receiving S. boulardii without clindamycin. The results suggest that S. boulardii warrants further evaluation for the prevention of antibiotic-associated colitis.

Gastric bicarbonate secretion: effect of topical and intravenous 16,16-dimethyl prostaglandin E2

Article

Aug 1980
Am J Physiol

These studies were designed to compare intravenous and topical 16,16-dimethyl prostaglandin E2 (dmPGE2) as stimulants of gastric mucosal HCO3- secretion. In six Heidenhain pouch (HP) dogs, basal acid secretion was inhibited by cimetidine. With 100 ml 0.15 M NaCl as the fluid circulating through the HP, intrapouch titration to pH 6.0 was performed with 0.5 M HCl as titrant. After measuring basal HCO-3 secretion for 30 min, dmPGE2 was given intravenously or the fluid circulating in the HP was replaced by one containing dmPGE2. Intravenous dmPGE2 at infusion rates of 0, 0.5, 1.0, and 2.0 microgram . kg-1 . h-1 produced alkaline secretion rates of 34 +/- 9, 52 +/- 20, 72 +/- 21, and 70 +/- 20 (SE) mu mol . h-1, respectively. Topical dmPGE2 at concentrations of 0, 0.05, 1.25, and 2.50 microgram . ml-1 produced alkaline secretion rates of 22 +/- 7, 74 +/- 16, 134 +/- 28, and 144 +/- 35 mu mol . h-1, respectively (P less than 0,05 for each concentration). Glucosamine output, as an index of mucus secretion, increased significantly with HCO-3 secretion. We conclude that intragastric titration is a valid method for recording HCO-3 secretion from an HP, that topical dmPGE2 stimulates HCO3- secretion more effectively than intravenous dmPGE2, and that topical dmPGE2 stimulates mucus secretion as well as HCO-3 secretion,

Ignarro LJ, Fukuto JM, Griscavage JM, Rogers NE, Byrns REOxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci USA 90:8103-8107

Article

Oct 1993

Nitric oxide (NO) in oxygen-containing aqueous solution has a short half-life that is often attributed to a rapid oxidation to both NO2- and NO3-. The chemical fate of NO in aqueous solution is often assumed to be the same as that in air, where NO is oxidized to NO2 followed by dimerization to N2O4. Water then reacts with N2O4 to form both NO2- and NO3-. We report here that NO in aqueous solution containing oxygen is oxidized primarily to NO2- with little or no formation of NO3-. In the presence of oxyhemoglobin or oxymyoglobin, however, NO and NO2- were oxidized completely to NO3-. Methemoglobin was inactive in this regard. The unpurified cytosolic fraction from rat cerebellum, which contains constitutive NO synthase activity, catalyzed the conversion of L-arginine primarily to NO3- (NO2-/NO3- ratio = 0.25). After chromatography on DEAE-Sephacel or affinity chromatography using 2',5'-ADP-Sepharose 4B, active fractions containing NO synthase activity catalyzed the conversion of L-arginine primarily to NO2- (NO2-/NO3- ratio = 5.6) or only to NO2-, respectively. Unpurified cytosol from activated rat alveolar macrophages catalyzed the conversion of L-arginine to NO2- without formation of NO3-. Addition of 30 microM oxyhemoglobin to all enzyme reaction mixtures resulted in the formation primarily of NO3- (NO2-/NO3- ratio = 0.09 to 0.20). Cyanide ion, which displaces NO2- from its binding sites on oxyhemoglobin, inhibited the formation of NO3-, thereby allowing NO2- to accumulate. These observations indicate clearly that the primary decomposition product of NO in aerobic aqueous solution is NO2- and that further oxidation to NO3- requires the presence of additional oxidizing species such as oxyhemoproteins.

The L-Arginine: Nitric Oxide Pathway Is the Major Source of Plasma Nitrite in Fasted Humans

Article

May 1995

15N guanidino-labelled L-arginine was infused into fasted human volunteers giving, at equilibrium, a stable 1:10 ratio of 15N to 14N arginine in the plasma. Separate GC-MS assays were used to compare the degree of enrichment of plasma arginine, nitrite and nitrate and thus define the quantitative relationship between the L-arginine:nitric oxide (NO) pathway and the formation of these oxides of nitrogen. 15N nitrite enrichments rose to 8.3% (SD 0.5), five hours after the start of the infusion. In contrast, 15N nitrate enrichments apparently rose to only 1.6% (SD 0.4) at this time. This discrepancy could be explained by our finding that the commonly used Tesch GC-MS nitrate assay is subject to considerable interference from non-nitrate sources in plasma. Taking this into account, nitrate enrichments were similar to those observed for plasma nitrite. These results therefore indicate that the measurement of these compounds in plasma is a valid indicator of NO generation in fasted humans.

Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn's disease with special respect to chronic diarrhea - A pilot study

Article

Feb 1993

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.

Relationship between gastric mucus synthesis, secretion and surface gel erosion measured in amphibian stomach in vitro

Article

Dec 1997

1. The layer of adherent mucus that protects the surface of the stomach reflects a dynamic balance between biosynthesis of glycoprotein, secretion of preformed mucus and erosion of the adherent gel layer. The present study is the first in which all these processes have been measured concomitantly and was undertaken to define interrelationships between the three parameters. 2. A chambered sac preparation of amphibian gastric mucosa is described. Biosynthesis was determined by specific incorporation of radiolabeled sugars into purified glycoprotein. Mucus secretion was determined by measuring the thickness of the adherent gel and erosion of the surface layer was assessed from the appearance of soluble mucin in the luminal solution. 3. 16,16-Dimethyl-prostaglandin (PG. E2 stimulated glucosamine incorporation by 10-fold, but did not alter the rate of incorporation of galactose. There was a rapid two-fold increase in the thickness of the adherent mucus layer but no change in the rate of erosion. Dibutyryl-cAMP also stimulated mucus release but, unlike PG, increased glycoprotein labelling by galactose. 4. Both distention or the application of a cholinergic agonist increased adherent mucus thickness. Stimulation of mucus release in response to carbachol was accompanied by a decrease in glycoprotein labelling by galactose. In contrast, the adrenergic agent noradrenaline decreased secretion but did not influence labelling. 5. These results indicate that biosynthesis and secretion of gastric mucus are subject to differential regulation. Moreover, the profile of incorporation of sugars in response to secreta-gogues also differs, indicating the need for caution when interpreting effects on glycoprotein biosynthesis.

Role of growth factors and their receptors in gastric ulcer healing

Article

Jun 2001

The repair of gastric ulcers requires the reconstitution of epithelial structures and the underlying connective tissue, including vessels and muscle layers. Several growth factors have been implicated in this process, since they are able to regulate important cell functions, such as cell proliferation, migration, differentiation, secretion, and degradation of extracellular matrix, all of which are essential during tissue healing. Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), hepatocyte growth factor (HGF), and trefoil factors (TFFs) are mainly involved in the reconstitution of the epithelial structures. Platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta) play a major role in the reconstitution of connective tissue, including vessels and smooth muscle cells, and provide the extracellular matrix substrate for cell migration and differentiation. The expression of these growth factors and their receptors is increased during ulcer healing and, in some cases, intracellular signaling related to receptor binding and transduction has been demonstrated. EGF, TGF-alpha and TFFs are normally present either in the gastric juice or in the mucosa, and may exert their effects immediately after damage, before newly synthesized EGF and TFFs are released from the ulcer margin. The inhibition of their effects by neutralizing antibodies may result in delayed ulcer healing, while the administration of recombinant or natural analogues may improve ulcer repair. In this review, we will summarize the basic molecular characteristics of some of these growth factors, and will discuss available evidence supporting their role in the ulcer repair process.

Mechanisms Involved in Protection Afforded by l-Arginine in Ibuprofen-Induced Gastric Damage: Role of Nitric Oxide and Prostaglandins

Article

Feb 2002

L-Arginine (L-arg) exhibits multiple biological properties and plays an important role in the regulation of different functions in pathological conditions. Many of these effects could be achieved on this amino acid serving as a substrate for the enzyme nitric oxide synthase (NOS). At the gastrointestinal level, recent reports revealed its protective activities involving a hyperemic response increasing the gastric blood flow. The aim of this study was to characterize the relationship between NOS activity/expression and prostaglandin changes (PGs) in rats gastric mucosa, with L-arg associated resistance to the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen (IBP). The protective effect of oral L-arg (100 mg/kg body wt), administerred together with IBP (100 mg/kg body wt, per os), was evident enough 90 min after drug administration, although a significant protection persisted for more than 6 hr. Pretreatment with N(G)-nitro-L-arginine (L-NNA) (40 mg/kg body wt, intraperitoneally), a competitive inhibitor of constitutive NOS, partly altered the protection afforded by the amino acid. In contrast, no changes could be observed after inducible NOS inhibition [aminoguanidine (AG) 50 mg/Kg body wt, intraperitoneally). L-arg, plus IBP, produced a significant increase of the cyclic GMP (cGMP) response in tissue samples from rat stomach, 90 min and 6 h after drug administration. iNOS activity and mRNA expression were higher in IBP-treated rats, and no differences were observed in inducible responses in the L-arg plus IBP group. No variations in the cNOS activity and expression were found among the different groups of animals assayed. The measurement of mucosal PGE2 content confirmed that biosynthesis of the eicosanoid is maintained by L-arg for over 90 min after IBP, while a total inhibition was observed 6 hr later. The mechanisms of the L-arg protective effect on the damaged induced by IBP could be explained by the different period after drug administration. The early phase is mediated by cyclooxygenase/prostaglandins pathway (COX/PGs) although NO liberated by cNOS and the guanylate cyclase/cGMP pathway could be also relevant. The later phase implicates inhibition of the iNOS/NO response.

Geranylgeranylacetone Protects Guinea Pig Gastric Mucosal Cells from Gastric Stressor-Induced Apoptosis

Article

Aug 2002

Various stressors induce apoptosis in gastric mucosal cells, which may cause gastric mucosal lesions in vivo. We recently reproduced gastric stressor-induced apoptosis in vitro, using primary cultures of guinea pig gastric mucosal cells. Geranylgeranylacetone is an antiulcer drug with heat-shock protein-inducing properties. The purpose of this study is to examine the effect of geranylgeranylacetone on gastric stressor-induced apoptosis in vitro. Ethanol, hydrogen peroxide, and hydrochloric acid all induced, in a dose-dependent manner, apoptotic DNA fragmentation. Pretreatment of cells with geranylgeranylacetone inhibited the apoptotic DNA fragmentation caused by each of these gastric stressors. Pretreatment of cells with a low concentration of ethanol, a procedure that is also known tb induce heat-shock proteins, made cells resistant to the apoptotic DNA fragmentation. These results suggest that heat-shock proteins could be at least partly involved in the inhibitory effect of geranylgeranylacetone against apoptosis of gastric mucosal cells caused by these gastric stressors.

Li J, Zhang YP, Kirsner RS.Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc Res Tech 60:107-114

Article

Jan 2003

Angiogenesis is critical to wound repair. Newly formed blood vessels participate in provisional granulation tissue formation and provide nutrition and oxygen to growing tissues. In addition, inflammatory cells require the interaction with and transmigration through the endothelial basement membrane to enter the site of injury. Angiogenesis, in response to tissue injury, is a dynamic process that is highly regulated by signals from both serum and the surrounding extracellular matrix (ECM) environment. Vascular endothelial growth factor, angiopoietin, fibroblast growth factor, and transforming growth factor beta are among those most potent angiogenic cytokines in wound angiogenesis. The cooperative regulation of them is essential for wound repair. Migration of endothelial cells and development of new capillary vessels during wound repair is dependent on not only the cells and cytokines present but also the production and organization of ECM components both in granulation tissue and in endothelial basement membrane. The ECM regulates angiogenesis by providing scaffold support and signaling roles. They also serve as a reservoir and modulator for growth factors. Laminins are the major noncollagenous ECM of endothelial basement membrane. Two newly recognized laminins, 8 and 10, are the major laminins produced by human dermal microvascular endothelial cells. Laminin 10 is highly expressed in blood vessels around skin wounds. Laminin 8 promotes dermal endothelial cell attachment, migration, and tubule formation. Integrins with either beta 1 or alpha v subunits are the major cellular surface receptors for ECM molecules and mediate the interactions between cells and ECM during wound angiogenesis.

Induction of Small Intestinal Damage in Rats Following Combined Treatment with Cyclooxygenase-2 and Nitric-Oxide Synthase Inhibitors

Article

Sep 2004

Nitric oxide (NO) produced by constitutively expressed NO synthase (cNOS) plays an important role in maintaining the mucosal integrity of the small intestine, in collaboration with prostaglandins produced by cyclooxygenase (COX)-1. We examined whether intestinal damage is provoked in rats under inhibition of both cNOS and COX-2. The animals were given L-NAME (N(G)-nitro-L-arginine methyl ester), aminoguanidine, or rofecoxib, either alone or in combination, and killed 24 h later. Neither L-NAME nor aminoguanidine alone provoked damage in the small intestinal mucosa within 24 h, yet L-NAME produced damage in a L-arginine-sensitive manner when administered together with rofecoxib. L-NAME up-regulated the expression of COX-2 mRNA, and the prostaglandin E(2) (PGE(2)) content following the L-NAME administration significantly increased 12 h later, in both a rofecoxib- and a L-arginine-inhibitable manner. L-NAME enhanced intestinal motility, decreased mucus secretion, and increased the number of bacteria in the mucosa. The up-regulation of COX-2 expression and PGE(2) production by L-NAME was inhibited by prior administration of atropine, at a dose that inhibited the intestinal hypermotility. The intestinal lesions induced by L-NAME plus rofecoxib were prevented by pretreatment with ampicillin and aminoguanidine as well as atropine, indicating the involvement of bacteria, inducible nitric oxide synthase, and hypermotility in the pathogenesis. These results suggest that inhibition of both cNOS and COX-2 provokes intestinal damage, similar to inhibition of both COX-1 and COX-2. Inhibition of cNOS, similar to COX-1, up-regulates COX-2 expression, the process being associated with intestinal hypermotility and bacterial invasion, and this may be a key to the occurrence of intestinal damage associated with COX-2 inhibition.

Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: A randomized double-blind placebo-controlled trial

Article

Apr 2005

Co-treatment with Saccharomyces boulardii appears to lower the risk of antibiotic-associated diarrhoea in adults receiving broad-spectrum antibiotics. To determine whether S. boulardii prevents antibiotic-associated diarrhoea in children. A total of 269 children (aged 6 months to 14 years) with otitis media and/or respiratory tract infections were enrolled in a double-blind, randomized placebo-controlled trial in which they received standard antibiotic treatment plus 250 mg of S. boulardii (experimental group, n = 132) or a placebo (control group, n = 137) orally twice daily for the duration of antibiotic treatment. Analyses were based on allocated treatment and included data from 246 children. Patients receiving S. boulardii had a lower prevalence of diarrhoea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) than those receiving placebo [nine of 119 (8%) vs. 29 of 127 (23%), relative risk: 0.3, 95% confidence interval: 0.2-0.7]. S. boulardii also reduced the risk of antibiotic-associated diarrhoea (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared with placebo [four of 119 (3.4%) vs. 22 of 127 (17.3%), relative risk: 0.2; 95% confidence interval: 0.07-0.5]. No adverse events were observed. This is the first randomized-controlled trial evidence that S. boulardii effectively reduces the risk of antibiotic-associated diarrhoea in children.

Inducible nitric oxide synthase involvement in the mechanism of action of Saccharomyces boulardii in castor oil-induced diarrhoea in rats

Article

Dec 2005

The biotherapeutic agent Saccharomyces boulardii has been shown to inhibit castor oil-induced diarrhoea in rats in a dose-response fashion, and one of the suggested mechanisms of action included involvement of the nitric oxide pathway. The present study was designed to address this mechanism of action by firstly measuring the effects of S. boulardii on the inducible nitric oxide synthase (iNOS) isoform activity in vitro. Second, the effects of S. boulardii on the increase in colonic citrulline level associated with castor oil treatment were examined. In vitro, S. boulardii showed a dose-dependent inhibition of iNOS activity with an IC50 of 0.89 mg/ml. In the rat diarrhoea model, the antidiarrhoeal effect of S. boulardii was confirmed using a single oral dose of 12 x 10(10) CFU/kg (viable cells). In this model, castor oil significantly elevated citrulline level from 2526+/-164 to 3501+/-193 nmol/g in the colon. When the rats were treated with the same antidiarrhoeal single dose of S. boulardii, no increase in citrulline level was observed. Moreover, the iNOS inhibitor 1400 W at 10 mg/kg and the inhibitor of iNOS expression dexamethasone at 1 mg/kg, administered subcutaneously, blocked the citrulline production induced by the laxative. Taken together, these findings confirm the involvement of inhibition of the inducible isoform of nitric oxide synthase in the mechanism of action of S. boulardii in diarrhoea.

Nitro-Arginine Methyl Ester, a Non-Selective Inhibitor of Nitric Oxide Synthase Reduces Ibuprofen-Induced Gastric Mucosal Injury in the Rat

Article

Oct 2005

Ibuprofen is a commonly used non-steroidal anti-inflammatory drug. Gastrointestinal adverse drug reactions from ibuprofen usage include gastric mucosal ulcers and bleeding. The mechanism by which ibuprofen induces gastric mucosal damage is not clear. The present study is an attempt to examine the role of nitric oxide in the pathogenesis of ibuprofen-induced gastric mucosal damage. Ibuprofen administered orally at the dose of 100 mg/kg body weight for 6 days to the rats resulted in gastric mucosal injury. Serum nitrite and nitrosothiol were increased significantly as compared with the controls, which were treated with the vehicle alone. In the gastric mucosa, lipid peroxidation and protein thiols were increased, and the activity of glyceraldehyde 3-phosphate dehydrogenase, a nitric oxide sensitive enzyme was decreased significantly. Pretreatment of the rats daily with nitric oxide synthase inhibitor, nitro-arginine methyl ester (30 mg/kg body weight) 1 hr before treatment with ibuprofen reduced the gastric mucosal injury. Biochemically, it prevented the rise in serum nitrite levels and the increase in lipid peroxidation and protein thiol levels and the loss of glyceraldehyde 3-phosphate dehydrogenase activity in the gastric mucosa. The results of the present study suggest that increased nitric oxide production may be one of the mechanisms by which ibuprofen produces gastric mucosal injury and that inhibition of nitric oxide synthase reduces gastric mucosal injury.

Saccharomyces boulardii Inhibits Inflammatory Bowel Disease by Trapping T Cells in Mesenteric Lymph Nodes

Article

Dec 2006
GASTROENTEROLOGY

Saccharomyces boulardii is a nonpathogenic yeast used for treatment of diarrhea. We used a mice model of inflammatory bowel disease (IBD) to analyze the effects of S boulardii on inflammation. Lymphocyte-transferred SCID mice, displaying IBD, were fed daily with S boulardii. Weight loss and inflammatory status of the colon were monitored. Nuclear factor-kappaB activity was assessed in the colon. The CD4(+) T-cell production of interferon (IFN) gamma was evaluated by enzyme-linked immunosorbent assay, and a comprehensive reverse-transcription polymerase chain reaction (RT-PCR) analysis for both colon and mesenteric lymph nodes was performed. Finally, we analyzed cell migration mechanisms in vitro and in vivo. S boulardii treatment inhibits IBD. S boulardii induces an accumulation of IFN-gamma-producing T-helper 1 cells within the mesenteric lymph nodes correlated with a diminution of CD4(+) T-cell number and IFN-gamma production by CD4+ T cells within the colon. The influence of S boulardii treatment on cell accumulation in mesenteric lymph nodes was also observed in normal BALB/c mice and involves modifications of lymph node endothelial cell adhesiveness by a yeast secretion product. S boulardii has a unique action on inflammation by a specific alteration of the migratory behavior of T cells, which accumulate in mesenteric lymph nodes. Therefore, S boulardii treatment limits the infiltration of T-helper 1 cells in the inflammed colon and the amplification of inflammation induced by proinflammatory cytokines production. These results suggest that S boulardii administration may have a beneficial effect in the treatment of IBD.

Saccharomyces boulardii in acute childhood diarrhoea: A randomized, placebo-controlled study

Article

Apr 2007

To evaluate the efficacy of the probiotic yeast Saccharomyces boulardii (S. boulardii) as an adjuvant to oral rehydration solution (ORS) in shortening the duration of acute infectious gastroenteritis in children less than 2 years old in ambulatory care. In a period of 1 year, 100 outpatients between 3 and 24 months old presenting with acute mild to moderate diarrhoea of less than 7 days duration, were included in a double-blind, randomized, placebo-controlled trial evaluating the efficacy of S. boulardii administered for 6 days. Twelve children were lost in follow-up; the data of 88 children could be analysed (44 in the placebo and 44 in the S. boulardii group). Seventy-two patients were followed for one month (37 in the placebo and 35 in the S. boulardii group) allowing the calculation of the duration of diarrhoea. The mean duration of diarrhoea was 6.16 days (range 2-13 days) in the placebo group and 4.70 days (range 2-10 days) in the S. boulardii group (p<0.05). On the 4th day, the patients in the S. boulardii group passed 2.5+/-1.4 stools/day versus 3.5+/-1.8 in the placebo group (p<0.001). The risk of having diarrhoea lasting more than 7 days was lower in the S. boulardii group (3/44 versus 12/44; RR 0.25; 95% CI 0.1-0.8). In no patient diarrhoea persisted longer than 14 days. A statistically significant difference was observed in the number of stools on the 4th and 7th day favouring the subgroup that received early treatment (within the first 48 h of the onset of diarrhoea). The administration of antibiotics before inclusion did not make any difference. S. boulardii as an adjuvant to ORS in ambulatory care in children less than 2 years old with mild or moderate acute diarrhoea decreased the duration of diarrhoea, accelerated recovery and reduced the risk of prolonged diarrhoea. The data also indicate increased efficacy if S. boulardii is administered within the first 48 h of the onset of diarrhoea.

Twenty-Five Years of Research on Saccharomyces boulardii Trophic Effects: Updates and Perspectives

Article

Jul 2008
DIGEST DIS SCI

Jean-Paul Buts

Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn's disease in remission

Article

Feb 2008
SCAND J GASTROENTERO

Crohn's disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. In volunteers, the lactulose/mannitol ratio was 0.005+/-0.0037, whereas this value was 0.021+/-0.01 in patients with CD (p=0.001). In the placebo group, there was an increase in lactulose/mannitol ratio by 0.004+/-0.010 (p=0.12) at the end of the third month. In the S. boulardii group, there was an improvement in intestinal permeability, with a decrease in the lactulose/mannitol ratio by 0.008+/-0.006 (p=0.0005) in the same period. Patients with CD in remission present alterations in the integrity of the intestinal mucosal barrier according to lactulose/mannitol ratio. S. boulardii added to baseline therapy improved intestinal permeability in these patients, even though complete normalization was not achieved.

Gastroprotective Effect of Saccharomyces boulardii in a Rat Model of Ibuprofen-Induced Gastric Ulcer

Abstract

No full-text available

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