Probiotics in gastroenterology

Probiotics are defined as live microorganisms of human origin. Their use may favorably influence human health and ameliorate or prevent certain diseases. Prebiotics are non-digestible foodstuffs (fiber, oligofructans - "colonic foods"), which enter the colon and are metabolized by the probiotics. Probiotics should fulfill the following criteria: Phenotypic and genotypic classification, no pathogenic properties, human origin, application in the living state, resistance to gastric acid and bile, ability to adhere to colonocytes, ability to colonize the gut, clinically proved favorable health-effect, and safety. Experimental and clinical studies supplied evidence of the possible use of probiotics in the following diseases: Traveler's diarrhea, antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, infantile diarrhea, rotavirus enteritis, inflammatory bowel disease, irritable bowel syndrome, colon cancer, peritonitis, acute pancreatitis, and diarrhea associated with HIV infection. Probiotics displayed the following effects in these studies: Involvement in production of essential nutrients of the colonic mucosa, beneficial effect on intestinal immunity, recovery of the disturbed gut mucosal barrier and prevention of microbial translocation, elimination of toxins and eradication of microbial pathogens, production of steroids from cholesterol and reduction of its pool in circulation, participation in regulation of intestinal functions, reduced incidence of chemically induced colon tumors in rodents. Probiotics open new therapeutic modalities in a number of diseases and it may be expected that their importance will increase with growing knowledge and experience.     

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.     

Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases

Probiotics are defined as nonpathogenic living microorganisms, including some commensal bacterial flora, which have beneficial effects on host health and disease prevention and/or treatment. Clinical trials have shown beneficial effects of probiotics on several human diseases, such as inflammatory bowel diseases (IBDs), which are among the most-studied diseases testing probiotics as a potential therapy. However, a significant question regarding clinical use of probiotics is the mechanism underlying the wide range of actions. Studies discussed in this review suggest 3 distinct cellular and molecular mechanisms for probiotic regulation in IBD therapy: 1) Probiotics block pathogenic bacterial effects by producing bactericidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium; 2) Probiotics regulate immune responses by enhancing the innate immunity and modulating pathogen-induced inflammation via toll-like receptor-regulated signaling pathways; and 3) Probiotics regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, enhancing barrier function, and stimulating protective responses. Probiotics modulate host cell signaling pathways, including Akt, mitogen-activated protein kinases, and nuclear factor-kappaB to mediate these intestinal epithelial functions. It is hoped that developing a mechanistic understanding of probiotic action will provide the rationale to support the development of new hypothesis-driven studies to define the clinical efficacy in preventive, adjunctive, or alternative treatments for IBD.     

Recommendations for probiotic use

Probiotics are live microbial organisms that are administrated as supplements or in foods to benefit the host. It is the recommendation that they may be helpful in the prevention and treatment of acute diarrhea in adults and children, the prevention of antibiotic-associated diarrhea in adults and children, and the maintenance of remission and prevention of pouchitis. Although early results indicate that probiotics may also be useful in immunologic modulation to prevent atopy, treatment of radiation intestinal disease, vaginosis, ulcerative colitis, and the irritable bowel syndrome, the studies available are not sufficient to say they are definitely helpful. Even fewer data are available to recommend probiotics for the treatment of H pylori and Crohn disease and for the prevention of cardiovascular risk factors or other degenerative diseases. Clearly, larger and better-designed studies of probiotics are necessary, including comparative and dose-ranging trials.     

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 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 and the gastrointestinal tract： Where are we in 2005？

Probiotic agents are live microbes or components ofmicrobes that have a positive effect on the host.Theyexert their action through interplay with the immunesystem of the host.Some of this effect is local andsome is systemic.The full story is yet to be discovered.Probiotics have a definite positive effect on rotavirusdiarrhea,post antibiotic diarrhea and pouchitis.Theirexact role in inflammatory bowel disease,irritablebowel syndrome,other forms of infectious diarrhea,and prevention of cancer is yet to be determined.Thisreview summarizes the data about probiotics in theseconditions.     

益生菌制剂在消化系统中的应用

益生菌制剂可以恢复肠道菌群平衡和黏膜屏障功能,从而治疗相关疾病,其安全性和有效性已在临床上得到验证。现就近年来益生菌制剂在抗生素相关性腹泻、溃疡性结肠炎、腹泻型肠易激综合征、功能性便秘和慢性肝病等常见消化道疾病中的临床应用作一概述,为更好地开发和医用益生菌制剂奠定基础。     

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.     

益生菌在肠病中的应用及安全性

益生菌是指含有活的、达到一定数量的特定微生物,能通过种植或定植改变某一部位的微环境,从而发挥其调节人体微生态平衡的独特作用。近10年来,作为一种新兴药物被广泛应用于治疗各类肠病,尤其体现在治疗溃疡性结肠炎和腹泻方面。益生菌主要通过增强肠道黏膜屏障、调节肠道免疫等来发挥其作用。此外,益生菌在用于治疗肠病方面还存在着安全性等问题。     

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.     

Probiotics for the Treatment of Inflammatory Bowel Disease

Probiotics are organisms which provide a desired and beneficial effect on human health. With recent evidence implicating a disruption in the balance of the gastrointestinal microbiome and intestinal immunity as a potential trigger for inflammatory bowel disease (IBD), there has been growing interest in using probiotics as an adjunct to standard anti-inflammatory and immune suppressing therapy. Animal models describe potential and plausible mechanisms of action for probiotics to counter inflammation of colonic mucosa. Although there are insufficient data to recommend probiotics in ulcerative colitis or Crohn's disease, good evidence supports the use of specific probiotics for maintenance of remission in pouchitis. Although there are limited regulatory standards for the agents, probiotics are relatively safe with minimal reported side effects or contraindications. More rigorous studies need to be published supporting efficacy and safety of these agents before they become a mainstay of IBD medical treatment.     

益生菌与消化道健康

人体胃肠道内细菌与宿主具有特殊的关系。胃肠道内细菌,特别是益生菌对维持肠黏膜屏障功能、调节机体免疫功能和促进营养物质的吸收具有重要作用,与人体健康密切相关。肠道菌群紊乱与功能性消化不良、腹泻、便秘、炎症性肠病等胃肠道症状和多种疾病有关,补充外源性益生菌具有较好的临床疗效。本文对肠内益生菌与消化健康的关系作一简要概述。     

Probiotics in inflammatory bowel disease: a critical review

Intestinal bacteria play a key role in inflammatory bowel disease. Probiotics attempt to modify disease by favourably altering bacterial composition, immune status, and inflammation. Until recently, probiotic therapy was considered 'folk' medicine, but there now is emerging interest on the part of the general public and scientific communities in the use of probiotics in human disease. This practical, evidence-based review examines probiotics as therapy for inflammatory bowel disease in humans. There are very few such published randomized clinical trials, but some data exist that possibly show an efficacy of probiotics as maintenance therapy in chronic relapsing pouchitis. Obstacles to providing probiotic therapy include selection of appropriate strains, poorly regulated probiotic quality standardization, processing and human biologic factors which impair probiotic viability, difficulty in maintaining new bacterial populations in the gut, and local product unavailability. Studies have focused on specific inflammatory bowel disease subgroups, limiting general applicability for the practitioner. Basic research highlights the importance of bacteria in these conditions, and the possibility that probiotics will modify physiological parameters. Well-designed, randomized clinical studies are still required to define the role of probiotics as therapeutic agents in inflammatory bowel disease.     

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.     

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.     

Probiotics and irritable bowel syndrome: rationale, putative mechanisms, and evidence of clinical efficacy

The irritable bowel syndrome (IBS) follows an acute, presumably infectious diarrheal illness in approximately 15% of patients. There may be a persistent, mild inflammatory state with changes in mucosal function or structure. Changes in the colonic bacterial flora reported in IBS seem related to predominant bowel. Colonic bacteria normally metabolize nutrients with the formation of gas and short chain fatty acids. The latter may induce propulsive contractions and accelerate colonic transit or they may enhance fluid and sodium absorption in the colon. This review addresses the mechanisms, rationale and current evidence for the efficacy of probiotics, including Lactobacilli, Bifidobacteria, and VSL#3, in the treatment of IBS. The mechanisms influenced by probiotics include immune function, motility, and the intraluminal milieu. Probiotics may suppress the low-grade inflammation associated with IBS or restore normal local immune function. Lactobacilli and Bifidobacteria subspecies are able to deconjugate and absorb bile acids, potentially reducing the colonic mucosal secretion of mucin and fluids that may contribute to functional diarrhea or IBS with diarrhea. Therapeutic trials show the potential benefit of Bifidobacteria or Lactobacilli species alone or in the specific probiotic combination, VSL#3, on symptoms in IBS. Colonic transit was retarded in IBS patients treated with VSL#3 without induction of significant changes in bowel function. In summary, probiotics are promising therapies in IBS.     

肠道菌群失调与功能性腹泻

功能性腹泻(functional diarrhea,FD)主要表现为排便频次的增多及粪便性状的改变,且至少75%不伴有腹痛。它是临床上常见的一种功能性肠病,其发病率仅位居肠易激综合征之后,我国的发病率显著低于西方国家,但在亚洲相对较高。FD的病因和发病机制复杂,而肠道菌群失调被认为是其主要致病因素之一,因此,调节肠道菌群失调、恢复肠道微生态平衡是治疗FD的有效途径,且国内外多项研究表明,应用微生态制剂可有效调节肠道菌群失调,并能明显缓解FD的症状。本文着重就FD和肠道菌群失调的关系及应用微生态制剂治疗FD的疗效作一概述。     

Intestinal microbiota,probiotics and prebiotics in inflammatory bowel disease

It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn’s disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment.     

Probiotics in the management of colonic disorders

Probiotics have been used in humans for almost a century and widely recommended for the treatment of a variety of ills assumed to be of colonic origin, including diarrhea, constipation, bloating, and flatulence. More recently, probiotics have been evaluated in the management of specific colonic disorders such as inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile colitis. It is evident that no two probiotics are exactly alike; why then should we expect reproducible results from studies that employ different species or strains, variable formulations, and diverse dosing schedules? When probiotics have been studied with the rigor appropriate to a new therapeutic modality, some coherent results have emerged: specific strains are effective in certain diarrheal states, irritable bowel syndrome, ulcerative colitis, and pouchitis, as well as in the prevention of C. difficile-related colitis. Even here, not to mention other colonic disorders, further adequately powered and appropriately designed trials are needed.