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.     

Bacteriotherapy using fecal flora: toying with human motions

The intestinal flora may play a key role in the pathogenesis of certain gastrointestinal (GI) diseases. Components of bowel flora such as Lactobacillus acidophilus and Bifidobacterium bifidus have long been used empirically as therapeutic agents for GI disorders. More complex combinations of probiotics for therapeutic bacteriotherapy have also recently become available, however the most elaborate mix of human-derived probiotic bacteria is, by definition, the entire fecal flora. Fecal bacteriotherapy uses the complete normal human flora as a therapeutic probiotic mixture of living organisms. This type of bacteriotherapy has a longstanding history in animal health and has been used sporadically against chronic infections of the bowel, especially as a treatment of last resort for patients with severe Clostridium difficile syndromes including recurrent diarrhea, colitis, and pseudomembranous colitis. Encouraging results have also been observed following infusions of human fecal flora in patients with inflammatory bowel disease, irritable bowel syndrome, and chronic constipation. The therapeutic use of fecal bacteriotherapy is reviewed here and possible mechanisms of action and potential applications explored. Published reports on fecal bacteriotherapy are few in number, and detail the results of small uncontrolled open studies and case reports. Nevertheless, given the promising clinical responses, formal research into fecal bacteriotherapy is now warranted.     

Probiotics in the treatment of human inflammatory bowel diseases: update 2008

Probiotic research and clinical trials have been forging ahead over the last decade. Although much has been learnt in relation to probiotic intestinal epithelial-mucosal immune interactions, the evidence for substantial clinical efficacy of probiotics continues to progress much slower. This review outlines the probiotic clinical studies before 2005 that formed the foundation of probiotic clinical trials in inflammatory bowel disease and then examines indepth those inflammatory bowel disease probiotic clinical trials published after 2005 that are leading to new understanding of the role of probiotics in the induction and remission of inflammatory bowel disease in humans.     

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.     

Probiotics and prebiotics in inflammatory bowel disease

Multiple studies of the immune system in patients with inflammatory bowel disease (IBD) have demonstrated the presence of altered intestinal mucosal immunity, probably genetically determined, giving rise to increased immunoreactivity against elements of the commensal flora. The basic strategy in the treatment of IBD is aimed at suppressing inflammatory responses. With the exception of studies of antibiotic therapy, little attention has been paid to modifying intestinal flora. Modification of intestinal flora through probiotics provides the possibility of acting microbiologically as well as immunologically. From the physiopathological point of view, the use of probiotics in IBD is a good therapeutic alternative. However, at present, studies with probiotics have only yielded positive results in highly specific situations. Secondary physiopathological data from clinical trials suggest a beneficial effect. However, this effect should be confirmed either in studies with a larger number of patients or by applying strategies that more effectively modify the composition of intestinal flora.     

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 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,infection and immunity

PURPOSE OF REVIEW: Taking live bacteria by mouth to improve health (probiotics) is not intuitively rational yet it is a practice with a long history. As interest in the effects on health of the intestinal flora has developed, along with major advances in the technology for studying it, so has come a new interest in establishing the true benefits of probiotic therapy. This review summarizes the most recent contributions to this rapidly developing area. RECENT FINDINGS: Probiotic bacteria, mainly bifidobacteria and lactobacilli for historical reasons, can prevent or ameliorate some diseases. Many empirical studies have been done, but work to develop the ideal characteristics of probiotics lags behind. Current literature covers survival of probiotics in the gut, mucosal adherence, antibacterial/pathogen mechanisms, effects on immune function and clinical studies. SUMMARY: Probiotic bacteria are effective in preventing and reducing the severity of acute diarrhoea in children. They are also useful in antibiotic associated diarrhoea but not for elimination of Helicobacter pylori. In inflammatory bowel disease, especially ulcerative colitis, probiotics offer a safe alternative to current therapy. Probiotics have been used to prevent urogenital tract infection with benefit and, perhaps more intriguingly, to reduce atopy in children. Probiotics do not invariably work and study of mechanisms is urgently needed.     

A Gastroenterologist's Guide to Probiotics

The enteric microbiota contribute to gastrointestinal health, and their disruption has been associated with many disease states. Some patients consume probiotic products in attempts to manipulate the intestinal microbiota for health benefit. It is important for gastroenterologists to improve their understanding of the mechanisms of probiotics and the evidence that support their use in practice. Clinical trials have assessed the therapeutic effects of probiotic agents for several disorders, including antibiotic- or Clostridium difficile-associated diarrhea, irritable bowel syndrome, and the inflammatory bowel diseases. Although probiotic research is a rapidly evolving field, there are sufficient data to justify a trial of probiotics for treatment or prevention of some of these conditions. However, the capacity of probiotics to modify disease symptoms is likely to be modest and varies among probiotic strains-not all probiotics are right for all diseases. The current review provides condition-specific rationale for using probiotic therapy and literature-based recommendations.     

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 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.     

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.     

鼠李糖乳杆菌干预肠道菌群及脂质代谢治疗代谢相关性脂肪性肝病的研究进展

代谢相关性脂肪性肝病(metabolic associated fatty liver disease, MAFLD)现已成为全世界最常见的慢性肝病,发病率在逐年增加,目前无临床特效药,其发病机制复杂,主要涉及肥胖、肠道菌群、胰岛素抵抗、环境、遗传等。近年来,益生菌在预防和治疗MAFLD中被广泛研究,鼠李糖乳杆菌(Lactobacillus rhamnosus, LGG)属乳杆菌属的经典益生菌菌株。大量研究证明,LGG可通过调节肠道菌群、改善肠黏膜屏障及降低胆固醇改善MAFLD。本文主要阐述LGG干预MAFLD的相关可能机制。     

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.     

Bacterial supplementation in the irritable bowel syndrome. A randomised doubleblind placebo-controlled crossover study

BACKGROUND: Symptoms of at least a subgroup of patients with irritable bowel syndrome may be associated with an alteration in gut flora. Studies on bacterial based therapy have yielded mixed results. AIMS: To determine if oral administration of the probiotic Lactobacillus casei strain GG under randomized placebo controlled conditions improves symptoms in irritable bowel syndrome patients with bloating related symptoms. PATIENTS: A total of 25 patients with clinically confirmed irritable bowel syndrome (Rome criteria) were enrolled in the study. METHODS: This was a randomised double-blind placebo-controlled crossover trial. Lactobacillus GG was administered as enterocoated tablets constituting a daily dosage of 10(10) colony forming units. Symptoms were assessed by daily symptom diaries and periodic questionnaires. RESULTS: Twenty-four patients were randomised; 19 (80%) female, mean age 40 years (range 24-60), mean duration of symptoms 4.9 years (range 0.5-18). Nineteen (80%) patients completed the study. No significant differences were found between Lactobacillus casei strain GG and placebo mean symptom scores for pain, urgency or bloating. A trend was noted, however, for a reduction in the number of unformed bowel motions on Lactobacillus casei strain GG treatment for patients with diarrhoea. CONCLUSIONS: Lactobacillus casei strain GG alone did not significantly improve symptoms in this irritable bowel syndrome subgroup. A "diarrhoea predominant" subgroup may warrant further investigation.     

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.     

Probiotics for the treatment of postoperative complications following intestinal surgery

Probiotics are living micro-organisms that belong to the normal enteric flora and exert a beneficial effect on health and well-being. The rationale for the therapeutic use of probiotics in pouchitis (the most frequent long-term complication following pouch surgery for ulcerative colitis) and postoperative recurrence in Crohn's disease is based on convincing evidence suggesting a crucial role for the endogenous intestinal microflora in the pathogenesis of these conditions. Positive results have been obtained with the administration of highly concentrated probiotic preparations in preventing the onset and relapses of pouchitis. Further controlled studies are needed to establish the efficacy of probiotics in the prophylaxis of postoperative recurrences of Crohn's disease and in the treatment of mild pouchitis.     

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.     

Probiotics as a treatment strategy for gastrointestinal diseases?

Current interest in probiotics is motivated not only by the clinical data showing efficacy of some probiotic bacteria but also by the increasing antibiotic resistance of pathogenic bacteria (particularly in hospitals) and the rise of consumers' demand for natural substitutes of drugs. Only few randomized, double-blind placebo-controlled human trials are available, and some involved only small numbers of patients. They are difficult to compare because of differences in probiotic strains employed, doses and formulation. Among probiotic applications, reduction of diarrhea is probably the best-documented effect confirmed by recent meta-analyses. Literature on Helicobacter pylori indicates that probiotics are unable to eradicate the infection but could be useful in decreasing infection levels and as adjuvants of therapy-associated side effects. Studies performed in inflammatory bowel disease suggest that high doses of probiotics and most likely a combination of different lactobacilli and bifidobacteria are more effective in decreasing inflammatory score and maintaining patients in remission than a single probiotic strain. Probiotic studies evaluating amelioration of symptoms in irritable bowel syndrome would require more sustained patient numbers. However, accumulated data is encouraging and suggests that efficacy is strain-dependent. Finally, too few probiotic intervention trials have been reported on colon cancer to allow any firm conclusion.     

Probiotics in arthralgia and spondyloarthropathies in patients with inflammatory bowel disease. Prospective randomized trials are necessary.

Arthralgias and spondyloarthropathies of the peripheral and axial joints are common in inflammatory bowel disease. Evidence for a strong association between these clinical manifestations and diseases of the joints has been provided by several clinical and epidemiological studies. Immunological studies have shown the presence of shared inflammatory cells both in the gut and the synovium in spondyloarthropathies. Genetic factors play a crucial role in the pathogenesis of spondyloarthropathies and inflammatory bowel disease. The role of the ubiquitous bacterial flora and pathogenic microorganisms present in the intestinal lumen may induce these joint diseases in patients with inflammatory bowel disease. In this review we will focus on the pathogenesis of spondyloarthropathies and arthralgia in patients suffering from inflammatory bowel disease. Based on preliminary clinical observations in patients with arthralgia and IBD, we put forward the hypothesis that probiotics may be helpful in the management of common extraintestinal manifestations such as arthralgia in patients with ulcerative colitis and Crohn's disease.