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 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.     

Alterations in human intestinal microflora during experimental diarrhoea

Large quantities of fluid administered through an intestinal tube caused alterations in small bowel bacteriology in four of seven subjects. In two normal individuals, colonic bacteria were found after fluid infusion in areas of the small bowel which previously had none. The faecal microflora was also altered by the fluid purge: anaerobes were reduced in some subjects and large numbers of Enterobacter species emerged in others.In a patient with pancreatic insufficiency and diarrhoea, the concentration of Enterobacter in the faeces was directly related to the number of bowel motions per day. Treatment with pancreatic enzymes curtailed the diarrhoea and markedly reduced these organisms. Intubation showed that Enterobacter were harboured in the small intestine and suppressed in the large bowel during periods of normal bowel action. Diarrhoea caused by pancreatic enzyme withdrawal or fluid purgation removed the colonic inhibition and allowed these organisms to appear in the faeces.Acidic diarrhoea induced by lactose feeding to three hypolactasic patients caused reductions in the numbers of E. coli in the stool but increases in Enterobacter species. Bacteroides also declined in one subject.Certain alterations in small and large bowel bacteriology observed in these forms of experimental diarrhoea have also been described in naturally occurring diarrhoea of diverse aetiologies.     

Current level of consensus on probiotic science--report of an expert meeting--London, 23 November 2009

The present paper summarizes the consensus views of a group of 9 European clinicians and scientists on the current state of scientific knowledge on probiotics, covering those areas where there is substantial evidence for beneficial effects and those where the evidence base is poor or inconsistent. There was general agreement that probiotic effects were species and often strain specific. The experts agreed that some probiotics were effective in reducing the incidence and duration of rotavirus diarrhoea in infants, antibiotic-associated diarrhoea in adults and, for certain probiotics, Clostridium difficile infections. Some probiotics are associated with symptomatic improvements in irritable bowel syndrome and alleviation of digestive discomfort. Probiotics can reduce the frequency and severity of necrotizing enterocolitis in premature infants and have been shown to regulate intestinal immunity. Several other clinical effects of probiotics, including their role in inflammatory bowel disease, atopic dermatitis, respiratory or genito-urinary infections or H.pylori adjuvant treatment were thought promising but inconsistent.     

News from the Cochrane Library: probiotics for the prevention of paediatric antibiotic-associated diarrhoea

Based on a meta-analysis published in 2006 on the prevention of paediatric antibiotic-associated diarrhoea with probiotics a Cochrane review by the same authors has been released within the current edition of the Cochrane Library (Issue 2, 2007). The per protocol analysis showed a relative risk for the incidence of AAD of 0.49 (0.32; 0.74). These findings could not be confirmed by the intention to treat analysis. These data are promising, but future studies will be necessary to clarify the role of probiotics for the prevention of AAD.     

Current level of consensus on probiotic science-Report of an expert meeting- London, 23 November 2009

The present paper summarizes the consensus views of a group of 9 European clinicians and scientists on the current state of scientific knowledge on probiotics, covering those areas where there is substantial evidence for beneficial effects and those where the evidence base is poor or inconsistent. There was general agreement that probiotic effects were species and often strain specific. The experts agreed that some probiotics were effective in reducing the incidence and duration of rotavirus diarrhoea in infants, antibiotic-associated diarrhoea in adults and, for certain probiotics, Clostridium difficile infections. Some probiotics are associated with symptomatic improvements in irritable bowel syndrome and alleviation of digestive discomfort. Probiotics can reduce the frequency and severity of necrotizing enterocolitis in premature infants and have been shown to regulate intestinal immunity. Several other clinical effects of probiotics, including their role in inflammatory bowel disease, atopic dermatitis, respiratory or genito-urinary infections or H.pylori adjuvant treatment were thought promising but inconsistent.     

Probiotics and Prebiotics in Infants and Children

Probiotics and prebiotics have a major influence on gastrointestinal flora composition. This review analyses the relationship between this change in flora composition and health benefits in children. Literature databases were searched for relevant articles. Despite exhaustive research on the subject in different indications, such as prevention and treatment of acute gastroenteritis, antibiotic associated diarrhea (AAD), traveler's diarrhea, inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori, necrotizing enterocolitis, constipation, allergy and atopic dermatitis, colic and extraintestinal infections, reports of clear benefits for the use of prebiotics and probiotics in pediatric disorders remain scarce. The best evidence has been provided for the use of probiotics in acute gastroenteritis and in prevention of AAD. However, AAD in children is in general mild, and only seldom necessitates additional interventions. Overall, the duration of acute infectious diarrhea is reduced by approximately 24 hours. Evidence for clinically relevant benefit in all other indications (inflammatory bowel disease, irritable bowel syndrome, constipation, allergy) is weak to nonexistent. Selected probiotic strains given during late pregnancy and early infancy decrease atopic dermatitis. Adverse effects have very seldom been reported. Since the risk seems minimal to nonexistent, prebiotics and probiotics may be helpful in the prevention and treatment of some disorders in children, although the evidence for benefit is limited. The best evidence has been accumulated for some lactobacilli strains and for Saccharomyces boulardii in the reduction of the duration of acute diarrhea due to gastroenteritis and prevention of AAD.     

Probiotics and chronic disease

In today's climate, changed lifestyles and the increased use of antibiotics are significant factors that affect the preservation of a healthy intestinal microflora. The concept of probiotics is to restore and maintain a microflora advantageous to the human body. Probiotics are found in a number of fermented dairy products, infant formula, and dietary supplements. Basic research on probiotics has suggested several modes of action beneficial for the human body and clinical research has proven its preventive and curative features in different intestinal and extraintestinal diseases. Chronic diseases cause considerable disablement in patients and represent a substantial economic burden on healthcare resources. Research has demonstrated a crucial role of nutrition in the prevention of chronic disease. Thus, positive, strain-specific effects of probiotics have been shown in diarrheal diseases, inflammatory bowel diseases, irritable bowel syndrome, and Helicobacter pylori-induced gastritis, and in atopic diseases and in the prevention of cancer. As the majority of probiotics naturally inhabit the human intestinal microflora, their use has been regarded as very safe. However, in view of the range of potential benefits on health that might be achieved by the use of some probiotic bacteria, major and thorough evaluation is still necessary. In conclusion, probiotics act as an adjuvant in the prevention and treatment of a wide variety of chronic diseases.     

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.     

Beneficial microbes: health or hazard?

Normal microbial flora support the health of the host by diverse mechanisms. When antibiotics, stress, disease or medications disrupt normal microflora, the ability to ward off infection by pathogens is compromised. The use of beneficial microbes (also known as biotherapeutic agents, probiotics, synbiotics) has been shown to be an effective therapeutic agent for some diseases. Various types of diarrhoea (antibiotic-associated diarrhoea, Clostridium difficile disease, traveller's diarrhoea) are most responsive to these beneficial microbes. Serious risks associated with these microbes are largely theoretical at this point, but the risks need to be studied as the use of these beneficial microbes increases in popularity. Beneficial microbes are living organisms used as therapeutic agents to restore the health of the host in times when normal microflora have been disturbed. The efficacy to prevent or treat diarrhoea has been documented in multiple large, placebo-controlled, blinded clinical trials with only a few of these beneficial microbes. Risks of these beneficial microbes are limited, but potential risks have not been extensively studied in large numbers of patients.     

Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea

Most cases of antibiotic-associated diarrhoea (AAD) are directly or indirectly due to the alteration of gut microflora by antibiotics. 'Functional' diarrhoea, usually limited to a mild and brief change in stool frequency, is considered as the most frequent pattern of AAD. Reduced carbohydrate fermentation and impaired metabolism of bile acids have been claimed as the potential causes of this transient digestive discomfort but a critical analysis of the data supporting these theories is necessary. Alternatively, changes in the gut flora ecosystem allow pathogens to proliferate. Clostridium difficile is responsible for approximately 10% of cases of AAD and almost all cases of antibiotic-associated pseudomembranous colitis. The level of evidence which supports the potential responsibility of other candidate pathogens (Klebsiella oxytoca, enterotoxin-producing Clostridium perfringens and Staphylococcus aureus, Candida) needs to be appreciated according to the updated postulates of causality relationships between a bacterium and a disease.     

益生菌在防治老年人抗生素相关性腹泻中的应用与思考

益生菌是一类能使其宿主获益的活体微生物,应用广泛,但目前并没有大数据支持其临床应用。很多临床研究证实了不同益生菌防治抗生素相关性腹泻（AAD）的有效性,但基于近年的数据,回答益生菌是否可降低老年人AAD发生率的科学依据尚显薄弱。总的来说,益生菌有着非常好的安全记录,特定人群包括AAD患者使用益生菌将会获益,但需要个体化。     

Clinical Uses of Probiotics

Probiotics are live nonpathogenic microorganisms. Many of these microorganisms are part of the normal human gut flora, where they live in a symbiotic relationship. Probiotics have been used to treat gastrointestinal (GI) and non-GI medical conditions. However, the data supporting their use are often conflicting, especially for non-GI-associated illnesses. The strongest evidence supporting the use of probiotics is related to the treatment of acute diarrhea and pouchitis. Atopic eczema in children and genitourinary infections are the only non-GI-related medical conditions where probiotics may have some beneficial effects. Product selection and dosing are not the same in all conditions, and the beneficial effects of each probiotic strain cannot be generalized.The purpose of this article is to provide most recent information about probiotics and its uses. In contrast with previously published reviews on probiotics, we also discuss the composition of various products (Table 1), indications for their use (Table 2), product selection, and dosing of probiotics.Probiotics are safe and appear to exert some beneficial effects in GI-related illnesses. The use of probiotics in non-GI illnesses is not sufficiently supported by current data.     

Effect of antimicrobial agents on the ecological balance of human microflora

The normal microflora acts as a barrier against colonisation of potentially pathogenic microorganisms and against overgrowth of already present opportunistic microorganisms. Control of growth of opportunistic microorganisms is termed colonisation resistance. Administration of antimicrobial agents, therapeutically or as prophylaxis, causes disturbances in the ecological balance between the host and the normal microflora. Most studies on the impact of antimicrobial agents on normal microflora have been carried out on the intestinal flora. Less is known on the effects on oropharyngeal, skin, and vaginal microflora. Disturbances in the microflora depend on the properties of the agents as well as of the absorption, route of elimination, and possible enzymatic inactivation and/or binding to faecal material of the agents. The clinically most common disturbances in the intestinal microflora are diarrhoea and fungal infections that usually cease after the end of treatment. A well-balanced microflora prevents establishment of resistant microbial strains. By using antimicrobial agents that do not disturb colonisation resistance, the risk of emergence and spread of resistant strains between patients and dissemination of resistant determinants between microorganisms is reduced. In this article, the potential ecological effects of administration of antimicrobial agents on the intestinal, oropharyngeal, and vaginal microflora are summarised. The review is based on clinical studies published during the past 10 years.     

Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate

Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation(FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, Pub Med was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.     

Role of prebiotics,probiotics, and synbiotics in management of inflammatory bowel disease: Current perspectives

Experimental evidence supports the fact that changes in the bowel microflora due to environmental or dietary factors have been investigated as implicating factors in the etiopathogenesis of inflammatory bowel disease(IBD). The amassing knowledge that the inhabited microbiome regulates the gut physiology and immune functions in IBD, has led researchers to explore the effectiveness of prebiotics, probiotics, and synbiotics in treating IBD. This therapeutic approach focuses on restoring the dynamic...     

益生菌在抗生素相关性腹泻和难辨梭状芽孢杆菌相关性腹泻预防中的作用

随着抗生素的广泛应用,抗生素相关性腹泻（AAD）和难辨梭状芽孢杆菌相关性腹泻（CDAD）在临床上日益受到重视。目前,益生菌治疗已成为预防AAD和CDAD的一种潜在手段,本文就益生菌在AAD和CDAD预防中的机制、有效性和安全性等方面作一综述。     

Antibiotics and probiotics in treatment of inflammatory bowel disease

Many experimental and clinical observations suggest that intestinal microflora plays a potential role in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics or probiotics represents a potentially effective therapeutic option. The available studies do not support the use of antibiotics in ulcerative colitis (UC). Antibiotics are effective in treating septic complications of Crohn's disease (CD) but their use as a primary therapy is more controversial, although this approach is frequently and successfully adopted in clinical practice. There is evidence that probiotic therapy may be effective in the prevention and treatment of mild to moderate UC. In contrast, a lack of successful study data at present precludes the widespread use of probiotics in the treatment of CD. Both antibiotics and probiotics appear to play a beneficial role in the treatment and prevention of pouchitis and further trials are warranted to fully quantify their clinical efficacy.     

Probiotics, antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in humans

Probiotics are living organisms which, when ingested, have a beneficial therapeutic effect. Examples are bacteria, especially Lactobacillus rhamnosus GG, and the yeast Saccharomyces boulardii. Controlled trials indicate a benefit of both of these in the prevention of antibiotic-associated diarrhoea. Other less effective probiotics are Lactinex, Enterococcus faecium and bifidobacteria. In the difficult clinical problem of recurrent Clostridium difficile disease, S. boulardii as an adjunct to antibiotics has shown benefit in controlled trials. There is, however, less convincing evidence for the efficacy of Lactobacillus GG in this disease. Additional controlled trials and safety studies are needed before there can be a widespread endorsement of probiotics for these two conditions.     

Faecal Short-Chain Fatty Acids in Patients with Antibiotic-Associated Diarrhoea,before and after Faecal Enema Treatment

Background: Antibiotic-associated diarrhoea (AAD) may range from mild disturbances to severe pseudomembranous colitis. Many antibiotics affect several intestinal microflora-associated characteristics, such as short-chain fatty acid (SCFA) pattern. In the present study we investigated SCFAs in 31 patients on admittance to the hospital for severe AAD. Nine patients were followed up more extensively after they had received an enema containing faecal microflora from a healthy person on a Western diet. Methods: Faecal SCFAs were determined by gas chromatography. The enema was characterized before use. Results: AAD patients showed significant disturbances in faecal SCFA pattern. Clinically, most enema-treated patients recovered within days and had no relapses within 18 months. Conclusions: Intestinal microflora showed great disturbances, and the amounts of SCFAs were reduced, although the diarrhoea was not related to total amount SCFAs. Administration of a faecal enema resulted in the clinical recovery of most patients with severe diarrhoea within 4 days.