Probiotics for children with diarrhea: an update

This review focuses on the efficacy of probiotics for diarrhea in children in different settings: day-care centers, diarrhea acquired in the hospital, antibiotic-associated diarrhea, and treatment of acute infectious diarrhea. For prevention of diarrhea acquired in day-care centers, 5 randomized and placebo-controlled trials have been published. Probiotics tested were Lactobacillus GG, Bifidobacterium lactis (alone or in combination with Streptococcus thermophilus), and Lactobacillus reuteri. The evidence of their efficacy in these settings is only modest: statistically significant for some strains only and in any case of minimal to mild clinical importance. Few trials have examined the potential role of probiotics in preventing the spread of diarrhea in hospitalized children, an event most commonly due to either rotavirus or Clostridium difficile, and they have yielded conflicting results. Overall, these studies provide only weak evidence on the efficacy of probiotics. On the other hand, a large number of trials on the role of probiotics in preventing the onset of antibiotic-associated diarrhea have been published. Most commonly employed probiotics were Lactobacillus GG, Bifidobacterium spp., Streptococcus spp., and the yeast Saccharomyces boulardii. In general, these trials do show clear evidence of efficacy, with the 2 most effective strains being Lactobacillus GG and S. boulardii. Today, we have a large number of published clinical trials on the role of probiotics in treating sporadic infectious diarrhea in children, and many of them are randomized, blinded, and controlled. They consistently show a statistically significant benefit and moderate clinical benefit of a few, well-identified probiotic strains-mostly Lactobacillus GG and S. boulardii, but also L. reuteri-in the treatment of acute watery diarrhea, primarily rotaviral, in infants and young children of developed countries. Such a beneficial effect seems to result in a reduction of diarrhea duration of little more than 1 day, and to be exerted mostly on diarrhea due to rotavirus. The effect is not only strain-dependent, but also dose-dependent, with doses of at least 10 billion/d being necessary.     

Probiotics for prevention of antibiotic-associated diarrhea

Antibiotic-associated diarrhea (AAD) occurs in approximately 25% of patients receiving antibiotics. Hospitalized patients with AAD are at increased risk for nosocomial infections and have a higher mortality. Probiotics are living microorganisms used to restore gut health by changing the intestinal microbiota. Several have been studied for the prevention of AAD. Five meta-analyses of trials of probiotics for the prevention of AAD have been performed. The results showed an overall reduction in the risk of AAD when probiotics were coadministered with antibiotics. McFarland conducted the largest meta-analysis to date analyzing 25 randomized controlled trials of probiotics for the prevention of AAD including 2810 subjects. More than half of the trials demonstrated efficacy of the probiotic. In particular, Lactobacillus GG, Saccharomyces boulardii, and the probiotic mixtures were effective. The Cochrane Database of Systematic Reviews published a review of the literature on the use of probiotics for the prevention of pediatric AAD, including 10 randomized trials testing 1986 children. The per protocol pooled analysis, but not the intent-to-treat analysis, showed that probiotics are effective for preventing AAD with the number needed to treat to prevent 1 case of diarrhea being 10. Lactobacillus GG, Bacillus coagulans, and S. boulardii appeared to be most effective. Probiotics are generally safe, however, they should be used with caution in patients who have compromise of either the immune system or the integrity of the intestinal mucosa, and in the presence of a central venous catheter.     

Probiotics in the prevention and treatment of gastrointestinal infections

Probiotics have been studied in a variety of GI infections, and are an appealing concept given their favorable safety profiles. Several placebo-controlled trials indicated that lactobacilli have a suppressive effect on H pylori infection. Although some studies reported improvement in H pylori eradication, others failed to confirm this. Controlled trials support the use of Lactobacillus GG and S boulardii for the prevention of AAD, and have demonstrated the effectiveness of S boulardii as adjunctive therapy for RCDAD. Several placebo-controlled trials showed a reduction in the severity and duration of acute diarrhea in children with use of Lactobacillus GG. Studies of probiotics for the prevention of traveler's diarrhea yielded conflicting results, and their routine use cannot be recommended in this setting. Preliminary evidence suggests a potential role for reducing secondary pancreatic infections, although conclusive evidence is not available at this time. Additional clinical trials are indicated to define the role of probiotics further before wide-spread use can be recommended.     

Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile diarrhea

Antibiotic-associated diarrhea is a common clinical problem occurring in up to 25% of patients, with diarrhea owing to Clostridium difficile accounting for up to a quarter of cases. The clinical and economic costs of antibiotic-associated diarrhea are significant and better treatments are needed. Probiotics may offer potential effective therapy for antibiotic-associated diarrhea by restoring intestinal microbial balance. A number of different probiotics have been evaluated in the prevention and treatment of antibiotic-associated diarrhea in adults and children, including the nonpathogenic yeast Saccharomyces boulardii and multiple lactic-acid fermenting bacteria such as Lactobacillus rhamnosus GG (LGG). A careful review of the literature supports the efficacy of S. boulardii in the prevention of antibiotic-associated diarrhea recurrent C. difficile infection in adults, whereas LGG is useful in the treatment of antibiotic-associated diarrhea in children. Not enough data exist to currently support the use of other probiotic preparations in these conditions. Although generally safe and well tolerated, both S. boulardii and LGG should be used cautiously in immunocompromised patients. Further study of probiotics, including large, well-designed, randomized controlled dose-ranging trials, comparative trials, and cost-benefit analyses are necessary.     

Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease

CONTEXT: Antibiotic-associated diarrhea (AAD) is a common complication of most antibiotics and Clostridium difficile disease (CDD), which also is incited by antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis. The use of probiotics for these two related diseases remains controversial. OBJECTIVE: To compare the efficacy of probiotics for the prevention of AAD and the treatment of CDD based on the published randomized, controlled clinical trials. DATA SOURCES: PubMed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and Cochrane Central Register of Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists, authors, reviews, commentaries, associated diseases, books, and meeting abstracts. STUDY SELECTION: Trials were included in which specific probiotics given to either prevent or treat the diseases of interest. Trials were required to be randomized, controlled, blinded efficacy trials in humans published in peer-reviewed journals. Trials that were excluded were pre-clinical, safety, Phase 1 studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of prebiotics, not the disease being studied, or inconsistent outcome measures. Thirty-one of 180 screened studies (totally 3,164 subjects) met the inclusion and exclusion criteria. DATA EXTRACTION: One reviewer identified studies and abstracted data on sample size, population characteristics, treatments, and outcomes. DATA SYNTHESIS: From 25 randomized controlled trials (RCTs), probiotics significantly reduced the relative risk of AAD (RR = 0.43, 95% CI 0.31, 0.58, p < 0.001). From six randomized trials, probiotics had significant efficacy for CDD (RR = 0.59, 95% CI 0.41, 0.85, p = 0.005). CONCLUSION: A variety of different types of probiotics show promise as effective therapies for these two diseases. Using meta-analyses, three types of probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG, and probiotic mixtures) significantly reduced the development of antibiotic-associated diarrhea. Only S. boulardii was effective for CDD.     

The use of probiotics in gastrointestinal disease.

Probiotics are living microorganisms that can affect the host in a beneficial manner. Prebiotics are nondigestible food ingredients that stimulate the growth and activity of probiotic bacteria already established in the colon. Efficacy of probiotic compounds has been shown in a wide range of gastrointestinal diseases. Lactobacillus GG alone, or the combination of Bifidobacterium bifidum and Streptococcus thermophilus, is effective in the treatment of Clostridium difficile, as well as in preventing the frequency and severity of infectious acute diarrhea in children. Prevention of antibiotic-induced diarrhea with the concomitant administration of either Lactobacillus GG or Saccharomyces boulardii has been demonstrated. The most successful studies involve the use of Lactobacillus GG at a dose of 1 x 1010 viable organisms per day and the yeast boulardii at a dose of 1 g/day. A probiotic preparation (VSL#3 - 6 g/day) that uses a combination of three species of Bifidobacterium, four strains of Lactobacillus and one strain of Streptocccus has shown promise in maintaining remission in ulcerative colitis and pouchitis, as well as in preventing the postoperative recurrence of Crohn's disease. The mechanism of action of probiotics may include receptor competition, effects on mucin secretion or probiotic immunomodulation of gut-associated lymphoid tissue. Oral administration of probiotic compounds has been demonstrated to be well tolerated and safe. However, while probiotics have the potential to improve human health and to prevent and treat some diseases, major improvements are needed in labelling and quality assurance procedures for probiotic compounds. In addition, well planned and controlled clinical studies are necessary to delineate fully the potential for probiotic compounds.     

Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials

To evaluate the evidence for the use of probiotics in the prevention of acute diarrhoea, we did a meta-analysis of the available data from 34 masked, randomised, placebo-controlled trials. Only one trial was community based and carried out in a developing country. Most of the remaining 33 studies were carried out in a developed country in a health-care setting. Evaluating the evidence by types of acute diarrhoea suggests that probiotics significantly reduced antibiotic-associated diarrhoea by 52% (95% CI 35-65%), reduced the risk of travellers' diarrhoea by 8% (-6 to 21%), and that of acute diarrhoea of diverse causes by 34% (8-53%). Probiotics reduced the associated risk of acute diarrhoea among children by 57% (35-71%), and by 26% (7-49%) among adults. The protective effect did not vary significantly among the probiotic strains Saccharomyces boulardii, Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus bulgaricus, and other strains used alone or in combinations of two or more strains. Although there is some suggestion that probiotics may be efficacious in preventing acute diarrhoea, there is a lack of data from community-based trials and from developing countries evaluating the effect on acute diarrhoea unrelated to antibiotic usage. The effect on acute diarrhoea is dependent on the age of the host and genera of strain used.     

Probiotics in gastroenterology: indications and future perspectives

Nowadays. there is a growing interest in probiotics as a safe way of changing the intestinal bacterial flora. Probiotics may have potential in several gastroenterological conditions, especially when the intestinal flora has been disturbed. Most scientific evidence is available for diarrhoea patients treated with Lactobacillus GG, Lactobacillus reuteri or Saccharomyces boulardii. Meta-analyses have shown an overall reduction in the risk of antibiotic-associated diarrhoea during treatment with probiotics, and benefits have also been demonstrated for patients with rota-virus-associated diarrhoea. Patients with inflammatory bowel disease, an inflammatory disorder characterized by a change in the intestinal flora, are another important target group for which probiotics may be beneficial. It has been claimed that in ulcerative colitis and Crohn disease patients, lactobacilli, S. boulardii and Escherichia coli reduce relapses. but most studies were not placebo-controlled. A reduction in relapses has also been demonstrated in pouchitis patients treated with a multispecies probiotic. Irritable bowel syndrome might be another clinical indication for probiotic therapy, but results of clinical trials performed in these patients are inconsistent. Additionally, probiotics may improve lactose absorption. Helicobacter pylori eradication and constipation. Finally, in animal models of colorectal cancer, treatment with probiotics reduces the prevalence of this disease, and in humans the amount of genotoxic substances in faeces has been reduced. In conclusion, the results of studies on the effects of probiotics in gastrointestinal conditions are encouraging. but well-designed placebo-controlled studies are warranted before recommendations for therapeutic or preventive use can be given. Many issues still have to be resolved, including optimal dose and duration of treatment, selection of and differences between the several available probiotic strains, and, importantly, their mechanisms of actions have to be elucidated.     

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

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

Micro-organisms administered in the benefit of the host: myths and facts

OBJECTIVE: To evaluate the published literature on the potential benefit of micro-organisms on the general well being of the host. STUDY DESIGN: All published prospective, randomized, placebo-controlled trials with micro-organisms to improve the health of the host were critically reviewed. RESULTS: According to published data, there is evidence suggesting that Lactobacillus rhamnosus strain GG or Lactobacillus casei strain GG and Saccharomyces boulardii may be of possible benefit for the treatment of several medical conditions. However, published data on the therapeutic effect of other micro-organisms are almost non-existent. CONCLUSION: Better designed prospective, randomized, and placebo-controlled studies are needed. Most of the present strains have not been selected in a rational way, but apparently represent rather randomly picked isolates. Although the theoretical advantages of micro-organisms administered to the benefit of the host are extremely interesting and promising, results of clinical trials are disappointing.     

Probiotics for children: use in diarrhea

The use of probiotics in diarrheal diseases of children is increasing. Probiotics, mostly lactic acid bacteria such as Lactobacilli and Bifidobacteria, but also the yeast Saccharomyces boulardii, have been tried in many double-blinded, randomized, placebo-controlled studies, and several well-conducted meta-analyses are now available. There is some evidence of efficacy in the prevention of community-acquired and nosocomial diarrhea. More solid evidence of efficacy is found in the treatment of sporadic, infectious diarrhea, where several probiotics, and especially Lactobacillus GG, have been found capable of reducing by approximately 1 day the duration of diarrhea, shorten the initial phase of watery stools, and reducing hospital stay in developed countries. The effect is best documented in viral diarrheas. Although there are valid conceptual premises for probiotics to be helpful in inflammatory bowel diseases, only 1 trial has been published in children, showing Lactobacillus GG not to be superior to placebo in maintaining remission of Crohn disease. All considered, more research is needed for a better understanding of the role of probiotics in gastrointestinal diseases of children, addressing issues such as pharmacokinetics, mechanism of action, and role of specific probiotics, alone or in combination, in different disorders.     

Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: a systematic review

OBJECTIVE: To evaluate the efficacy of Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea. DATA SOURCES: A computer-based search of MEDLINE, CINAHL, AMED, the Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews was conducted. A hand-search of the bibliographies of relevant papers and previous meta-analyses was undertaken. REVIEW METHODS: Trials were included in the review if they compared the effects of L. rhamnosus GG and placebo and listed diarrhoea as a primary end-point. Studies were excluded if they were not placebo-controlled or utilised other probiotic strains. RESULTS: Six trials were found that met all eligibility requirements. Significant statistical heterogeneity of the trials precluded meta-analysis. Four of the six trials found a significant reduction in the risk of antibiotic-associated diarrhoea with co-administration of Lactobacillus GG. One of the trials found a reduced number of days with antibiotic-induced diarrhoea with Lactobacillus GG administration, whilst the final trial found no benefit of Lactobacillus GG supplementation. CONCLUSION: Additional research is needed to further clarify the effectiveness of Lactobacillus GG in the prevention of antibiotic-associated diarrhoea.     

Meta-analysis of probiotics for the prevention of traveler's diarrhea

BACKGROUND: Traveler's diarrhea (TD) is a common health complaint among travelers. Rates of TD can range from 5% to 50%, depending on the destination. The use of probiotics for this disease remains controversial. The objective of this study was to compare the efficacy of probiotics for the prevention of TD based on published randomized, controlled clinical trials. METHODS: PubMed, Google Scholar, metaRegister, NIH registry of clinical trials and Cochrane Central Register of Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists, authors, reviews, commentaries, associated diseases, books and meeting abstracts. Inclusion criteria included: randomization, controlled, blinded, efficacy trials, in humans, peer-reviewed journals. Exclusion criteria were: pre-clinical, safety, phase 1 studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of prebiotics, and inconsistent outcome measures. RESULTS: Twelve of 940 screened studies met the inclusion and exclusion criteria. The pooled relative risk indicates that probiotics significantly prevent TD (RR=0.85, 95% CI 0.79,0.91, p<0.001). CONCLUSION: Several probiotics (Saccharomyces boulardii and a mixture of Lactobacillus acidophilus and Bifidobacterium bifidum) had significant efficacy. No serious adverse reactions were reported in the 12 trials. Probiotics may offer a safe and effective method to prevent TD.     

Indications for the use of probiotics in gastrointestinal diseases

Probiotics are live microbial organisms that are present in foods or dietary supplements and that confer health benefits to the host when ingested in sufficient quantities. Probiotics can be bacterial (e.g. Bifidobacteria spp. and Lactobacillus spp.) or yeasts (e.g. Saccharomyces boulardii). The administration of probiotics is often believed to be by and large beneficial for individuals with inflammatory or infectious diseases of the gastrointestinal tract. These positive effects are generally attributed to the ability of probiotics to regulate intestinal permeability, normalize host intestinal flora, improve gut immune barrier function, and equilibrate the balance between proinflammatory and anti-inflammatory cytokines. Of note, however, these claims are not always substantiated by findings from properly conducted clinical trials. Of particular importance, even when results from randomized controlled trials support the beneficial effects of a particular probiotic for a specific indication, the benefits achieved by the probiotic are generally not translatable to other probiotic formulations. This review discusses the gastrointestinal indications for probiotic use and describes the level of evidence that supports the use of specific probiotics for these indications. Several indications are addressed, including enteric infections, gastritis caused by Helicobacter pylori infection, necrotizing enterocolitis, inflammatory bowel diseases, and irritable bowel syndrome.     

Probiotics in infective diarrhoea and inflammatory bowel diseases

Bacteria are present throughout the gastrointestinal tract, but their pattern and concentration vary greatly. Probiotics are living organisms that supply beneficial health effects to the host. So far the beneficial effects of probiotics have been shown, almost exclusively, under poorly defined experimental conditions. There are little convincing data from well-designed, double-blind controlled trials supporting health-promoting effects. The use of probiotics to treat gastrointestinal infections has produced contrasting results. Apart from information on rotavirus infection in children, there is no convincing evidence from controlled studies on the efficacy of probiotics in the prevention or treatment of infective diarrhoea. However, experimental and clinical studies suggest that there are potential therapeutic roles for probiotics in the treatment of inflammatory bowel diseases. This review focuses on the available data concerning the mechanisms of action of probiotics, and on the results from clinical studies using probiotics to treat infective diarrhoea and inflammatory bowel disease.     

Cyclopropane fatty acid synthase mutants of probiotic human-derived Lactobacillus reuteri are defective in TNF inhibition

Probiotics are live microorganisms that confer health benefits to the host when administered in adequate amounts. Many probiotic strains are now marketed to consumers and include organisms such as lactobacilli, streptococci, bifidobacteria, Escherichia coli Nissle 1917, and the yeast Saccharomyces cerevisiae strain, “Saccharomyces boulardii”. In general, probiotics are considered safe for human consumption based on previous clinical trials, epidemiological studies, and historical usage in fermented foods. A subset of these probiotics have been derived from commensal bacteria indigenous to Homo sapiens. One such indigenous Lactobacillus species, Lactobacillus reuteri, includes a variety of strains derived from human breast milk and the gastrointestinal tract. The mechanisms by which commensal-derived probiotics promote health and combat diseases are poorly understood. Possible mechanisms include improving nutrient absorption, pathogen exclusion, strengthening intestinal barrier function and regulation of the immune system. A better understanding of how probiotics influence health is critical to fully optimize the integrative physiology of commensal microbial communities and mammalian hosts.     

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii(S.boulardii) for various disease indications in adults based on the peerreviewed,randomized clinical trials and pre-clinical studies from the published medical literature(Medline,Clinical Trial websites and meeting abstracts) between 1976 and 2009.For meta-analysis,only randomized,blinded controlled trials unrestricted by language were included.Pre-clinical studies,volunteer studies and uncontrolled studies were excluded fr...     

Probiotics as therapeutic agents in irritable bowel syndrome

Probiotics are defined as living micro-organisms which, when administered in large amounts, confer a health benefit on the host. The use of probiotics in the therapy of infectious bowel diseases as well as maintaining remission of ulcerative colitis and in pouchitis is evidence-based. Also, in several studies proof could be supplied that specific probiotics relieve the symptoms and the course of irritable bowel syndrome. Some trials showed a significant improvement of irritable bowel syndrome-related constipation via Lactobacillus casei Shirota and E. coli Nissle 1917. Lactobacillus plantarum has been proven effective in reducing pain and abdominal bloating. However, in most of the studies rather small numbers of patients were examined. Furthermore, these studies do not always closely follow scientific standards (randomised, double-blind, placebo-controlled). Therefore, confirmatory studies are necessary to examine the effect of probiotics in irritable bowel syndrome.     

Treatment of recurrent Clostridium difficile-associated disease

Recurrent Clostridium difficile-associated disease (RCDAD) is a difficult treatment problem--once a patient has one recurrence of the disease the likelihood of further recurrences is markedly increased. Repeat antibiotics are usually indicated, either metronidazole or vancomycin. Tapering and pulsing the antibiotic dose after a 10-day standard course decreases the incidence of recurrences compared with abruptly stopping antibiotics after a simple 10-day course. If recurrences continue after two courses of metronidazole, vancomycin may be preferable to avoid the risk of neurotoxicity that is associated with prolonged metronidazole use. There is also a role for probiotics in the treatment of RCDAD; Saccharomyces boulardii has been shown to decrease recurrences by about 50%, especially when combined with high-dose vancomycin. Other microbiologic approaches include the restoration of normal colonic flora by fecal enema or by nasogastric tube, but these have not been studied in controlled trials. In addition, there are numerous new treatment approaches that are under development, including a vaccine, which promise to aid the future treatment of RCDAD as well as prevention of initial CDAD.     

Are probiotics useful in Helicobacter pylori eradication?

Helicobacter pylori(H. pylori) is considered an etiologic factor for the development of peptic ulcer disease,gastric adenocarcinoma, and MALT lymphoma.Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries.Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H.pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L.johnsonni La1 probably can diminish the bacterial load,but not completely eradicate the H. pylori bacteria.Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii,L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects.