Probiotics and prebiotics in chronic inflammatory bowel diseases

INTRODUCTION At birth, the gastrointestinal tract is a sterile environment. Initial exposure of the gut to microbes occurs during the birthing process from the maternal fecal and vaginal ? ora. Within a few months after birth, a relatively stable microbia…     

Prebiotics in chronic intestinal inflammation

Prebiotics are nondigestible fermentable fibers that are reported to have health benefits for the host. Older as well as more recent studies show beneficial effects in experimental colitis and lately also in human inflammatory bowel diseases (IBD), such as Crohn's disease, ulcerative colitis, and chronic pouchitis. In this review we give an overview of the benefits of prebiotics in rodent IBD models and in IBD patients and discuss their possible protective mechanisms. Commensal intestinal bacteria induce and perpetuate chronic intestinal inflammation, whereas others are protective. However, most of the current medications are directed against the exaggerated proinflammatory immune response of the host, some of them toxic and costly. Feeding prebiotics changes the composition of the intestinal microflora toward more protective intestinal bacteria and alters systemic and mucosal immune responses of the host. Therapy for IBD targeting intestinal bacteria and their function is just emerging. Prebiotics have the promise to be relatively safe, inexpensive, and easy to administer. Unraveling their protective mechanisms will help to develop rational applications of prebiotics. However, the initial promising results with dietary prebiotics in preclinical trials as well as small studies in human IBD will need to be confirmed in large randomized controlled clinical trials.     

Gut microbiota and inflammatory bowel disease

Bacteria play an important role in the pathogenesis of inflammatory bowel disease (IBD), its complications and its symptoms. Antibiotics can decrease tissue invasion and eliminate aggressive bacterial species. They are used in IBD to treat infective complications and for altering bacterial flora, which may result in specific anti-inflammatory effects. In addition, suppression of bacterial metabolic activities or direct effects of antibiotics on intestinal structures and functions may result in symptoms which cannot be differentiated from symptoms caused by inflammation. Although current clinical trials do not fulfill criteria of evidence-based treatment, a few placebo- or standard treatment-controlled studies suggest that metronidazole and ciprofloxacin are effective in Crohn's colitis and ileocolitis, perianal fistulae and pouchitis. Administration of probiotics, prebiotics and synbiotics can restore a predominance of beneficial species. However, beneficial effects of probiotics in IBD are modest, strain-specific and limited to certain manifestations of disease and duration of use of the probiotic. For probiotics there is reasonable evidence of efficacy in relapse prevention in chronic pouchitis and ulcerative colitis, and suggestive evidence for postoperative prevention in pouchitis. Therapeutic manipulation of the intestinal flora offers considerable promise for treating IBD, but must be supported by large controlled therapeutic trials before widespread clinical acceptance. These agents may become a component of treating IBD in combination with traditional anti-inflammatory and immunosuppressive agents. Probiotic strategies, based on metagenomic or metabonomic analyses, and new classes of probiotics might play an important role in the future management of IBD.     

Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics

Crohn's disease, ulcerative colitis, and pouchitis are caused by overly aggressive immune responses to a subset of commensal (nonpathogenic) enteric bacteria in genetically predisposed individuals. Clinical and experimental studies suggest that the relative balance of aggressive and protective bacterial species is altered in these disorders. Antibiotics can selectively decrease tissue invasion and eliminate aggressive bacterial species or globally decrease luminal and mucosal bacterial concentrations, depending on their spectrum of activity. Alternatively, administration of beneficial bacterial species (probiotics), poorly absorbed dietary oligosaccharides (prebiotics), or combined probiotics and prebiotics (synbiotics) can restore a predominance of beneficial Lactobacillus and Bifidobacterium species. Current clinical trials do not fulfill evidence-based criteria for using these agents in inflammatory bowel diseases (IBD), but multiple nonrigorous studies and widespread clinical experience suggest that metronidazole and/or ciprofloxacin can treat Crohn's colitis and ileocolitis (but not isolated ileal disease), perianal fistulae and pouchitis, whereas selected probiotic preparations prevent relapse of quiescent ulcerative colitis and relapsing pouchitis. These physiologic approaches offer considerable promise for treating IBD, but must be supported by rigorous controlled therapeutic trials that consider clinical disease before their widespread clinical acceptance. These agents likely will become an integral component of treating IBD in combination with traditional anti-inflammatory and immunosuppressive agents.     

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.     

益生菌对炎症性肠病的治疗作用和机制

炎症性肠病包括溃疡性结肠炎和克罗恩病.炎症性肠病患者肠道内存在茵群失调,若给患者补充正常细菌即益生菌,使肠道内菌群失调得到纠正,可使病情缓解.益生菌能改变肠道菌群比例、转化某些肠内物质、提高肠上皮的屏障功能、防止肠细菌易位以及通过调节细胞因子减轻炎症.本文对益生菌以上作用及机制作一综述.     

Rationale for probiotic treatment strategies in inflammatory bowel disease

Chronic inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, are recurrent and aggressive inflammatory disorders that are most likely the result of an overly aggressive immune response to ubiquitous intestinal antigens in a genetically susceptible host. Despite decades of intense research, our knowledge of factors causing IBD remains incomplete and, therefore, conventional therapy to induce and maintain remission works in a symptomatic fashion, merely suppressing the immune response. Probiotic bacteria have long been known to confer health benefits, especially with regard to intestinal disorders. Although there is mounting evidence from in vitro and animal experiments supporting the use of probiotics in IBD, clinical trials have not provided definite evidence for the therapeutic effect of probiotic therapy in IBD to date. This is with the notable exception of pouchitis and the maintenance of remission in ulcerative colitis, whereas Crohn’s disease and active ulcerative colitis do not seem amenable to probiotic intervention. The next 5 years will see more trials targeting specific clinical settings using tailor-made probiotic combinations, taking into account our increasing knowledge of individual probiotic properties and the diversity of these microorganisms.     

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.     

The role of antibiotic and probiotic therapies in current and future management of inflammatory Bowel disease

Abundant evidence indicates that the intestinal microflora have a role in the pathogenesis of inflammatory bowel disease (IBD). The composition of the gut microflora is altered in IBD patients with increased "pathogenic" bacteria and decreased bifidobacteria and lactobacilli. In light of this dysbiosis, various methods have been examined to alter the composition of the intestinal microflora, including the administration of antibiotics and introduction of probiotic species. This article summarizes studies evaluating the efficacy of antibiotics and probiotics in the induction and maintenance of remission of ulcerative colitis, Crohn’s disease, and pouchitis.     

Use of probiotics in the treatment of inflammatory bowel disease

The gut flora plays a fundamental role in maintaining normal intestinal function. A disturbance of this flora, or the host response to this flora, has been clearly demonstrated to play a role in the pathogenesis of inflammatory bowel disease (IBD). This has led to attempts to modify the bacterial flora with "live non-pathogenic organisms that confer health benefits by improving the microbial balance," otherwise known as probiotics. Recent attention has focused on this potential strategy to treat or prevent IBD. The potential therapeutic benefit is enhanced by the natural and apparently safe approach that probiotics offer. Animal models of colitis have provided the proof of principle that probiotics can prevent and treat established intestinal inflammation. Controlled clinical studies have demonstrated the efficacy of probiotics in the maintenance of remission of pouchitis, prophylaxis of pouchitis after the formation of an ileoanal reservoir, maintenance of remission of ulcerative colitis, and treatment of Crohn's disease. However, large controlled trials are needed to definitively establish the place for probiotics in the treatment of IBD and resolve issues such as the dose, duration, frequency of treatment, and use of single or multiple strains. Research is focusing on establishing the mechanism of action, so that treatments with individually tailored properties are developed and innovative approaches are explored.     

Probiotics and prebiotics in ulcerative colitis

The intestinal microbiota is one of the key players in the etiology of ulcerative colitis. Manipulation of this microflora with probiotics and prebiotics is an attractive strategy in the management of ulcerative colitis. Several intervention studies for both the induction and maintenance of remission in ulcerative colitis patients have been performed. Most of these studies evaluated VSL#3 or E. Coli Nissle 1917 and in general there is evidence for efficacy of these agents for induction and maintenance of remission. However, studies are frequently underpowered, lack a control group, and are very heterogeneous investigating different probiotic strains in different study populations. The absence of well-powered robust randomized placebo-controlled trials impedes the widespread use of probiotics and prebiotics in ulcerative colitis. However, given the promising results that are currently available, probiotics and prebiotics may find their way to the treatment algorithm for ulcerative colitis in the near future.     

Diet therapy for inflammatory bowel diseases: The established and the new

Although patients with inflammatory bowel diseases(IBD) have a strong interest in dietary modifications as part of their therapeutic management, dietary advice plays only a minor part in published guidelines. The scientific literature shows that dietary factors might influence the risk of developing IBD, that dysbiosis induced by nutrition contributes to the pathogenesis of IBD, and that diet may serve as a symptomatic treatment for irritable bowel syndrome-like symptoms in IBD. The role of nutrition in IBD is underscored by the effect of various dietary therapies. In paediatric patients with Crohn’s disease(CD) enteral nutrition(EN) reaches remission rates similar to steroids. In adult patients, however, EN is inferior to corticosteroids. EN is not effective in ulcerative colitis(UC). Total parenteral nutrition in IBD is not superior to steroids or EN. The use of specific probiotics in patients with IBD can be recommended only in special clinical situations. There is no evidence for efficacy of probiotics in CD. By contrast, studies in UC have shown a beneficial effect in selected patients. For patients with pouchitis, antibiotic treatment followed by probiotics, like VSL#3 or Lactobacillus GG, is effective. When probiotics are used, the risk of bacterial translocation and subsequent bacteremia has to be considered. More understanding of the normal intestinal microflora, and better characterization of probiotic strains at the phenotypic and genomic levels is needed as well as clarification of the mechanisms of action in different clinical settings. A FODMAP reduced diet may improve symptoms in IBD.     

Intestinal microbiota: The explosive mixture at the origin of inflammatory bowel disease?

Inflammatory bowel diseases(IBDs), namely Crohn's disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origin of IBDs is closely linked to immune response alterations, which governs most medical decision-making, recent findings suggest that gut microbiota may be involved in IBD pathogenesis. Epidemiologic evidence and several studies have shown that a dysregulation of gut microbiota(i.e., dysbiosis) may trigger the onset of intestinal disorders such as IBDs. Animal and human investigations focusing on the microbiota-IBD relationship have suggested an altered balance of the intestinal microbial population in the active phase of IBD. Rigorous microbiota typing could, therefore, soon become part of a complete phenotypic analysis of IBD patients. Moreover, individual susceptibility and environmental triggers such as nutrition, medications, age or smoking could modify bacterial strains in the bowel habitat. Pharmacological manipulation of bowel microbiota is somewhat controversial. The employment of antibiotics, probiotics, prebiotics and synbiotics has been widely addressed in theliterature worldwide, with the aim of obtaining positive results in a number of IBD patient settings, and determining the appropriate timing and modality of this intervention. Recently, novel treatments for IBDs, such as fecal microbiota transplantation, when accepted by patients, have shown promising results. Controlled studies are being designed. In the near future, new therapeutic strategies can be expected, with non-pathogenic or modified food organisms that can be genetically modified to exert anti-inflammatory properties.     

Probiotics in the treatment of inflammatory bowel disease

The demonstration that immune and epithelial cells can discriminate between different microbial species has extended our understanding of the actions of probiotics beyond simple antimicrobial concepts. Several probiotic mechanisms of action, relative to inflammatory bowel disease, have been elucidated: (1) competitive exclusion, whereby probiotics compete with microbial pathogens; (2) immunomodulation and/or stimulation of an immune response; (3) antimicrobial activity and suppression of pathogen growth; (4) enhancement of barrier activity; and (5) induction of T cell apoptosis. The unraveling of these mechanisms of action has led to new support for the use of probiotics in the management of clinical inflammatory bowel disease. While level 1 evidence now supports the therapeutic use of some probiotics in the maintenance treatment of pouchitis, only level 2 and 3 evidence are currently available in support of the use of probiotics in the treatment of ulcerative colitis and Crohn's disease. Nevertheless, one significant and consistent finding has emerged over the course of research in the past year: not all probiotic bacteria have similar therapeutic effects. Rigorously designed, controlled clinical trials, to investigate the unresolved issues related to efficacy, dose, duration of use, single or multistrain formulation, and the concomitant use of prebiotics, synbiotics or antibiotics, are vital.     

Probiotics and inflammatory bowel disease: is there a scientific rationale?

Most conventional forms of drug therapy suppress or modify the host immunoinflammatory response and neglect the other contributor to disease pathogenesis-the environmental microflora. Probiotics are live microbial food ingredients that alter the enteric microflora and have a beneficial effect on health. The rationale for using probiotics in IBD is mainly based on evidence from human studies and experimental animal models implicating intestinal bacteria in the pathogenesis of these disorders. The relationship between bacteria and intestinal inflammation is complex and does not appear to reflect a simple cause and effect. Similarly, the field of probiotics is complex and in need of rigorous research. Until the indigenous flora are better characterized and mechanisms of probiotic action defined, the promise of probiotics in IBD is unlikely to be fulfilled. Because of strain-specific variability and clinical and therapeutic heterogeneity within Crohn's disease and ulcerative colitis, it cannot be assumed that a given probiotic is equally suitable for all individuals. Although preliminary results of probiotic therapy in animal models and humans with ulcerative colitis and pouchitis have been encouraging, their efficacy in treatment or maintenance of remission of Crohn's disease remains to be clarified. However, the circumstantial evidence for some form of biotherapeutic modification of the enteric flora in Crohn's disease seems compelling. In the future, probiotics may offer a simple adjunct to conventional therapy with the emphasis on diet shifting from one of nutritional replenishment alone to a more functional role.     

The intestinal microbiota and chronic disorders of the gut

Mucosal surfaces of the gut are colonized by large numbers of heterogeneous bacteria that contribute to intestinal health and disease. In genetically susceptible individuals, a 'pathogenic community' may arise, whereby abnormal gut flora contributes to alterations in the mucosa and local immune system leading to gastrointestinal disease. These diseases include enteric infections, such as Clostridium difficile infection, small intestinal bacterial overgrowth, functional gastrointestinal disorders (including IBS), IBD and colorectal cancer. Prebiotics, probiotics and synbiotics (a combination of prebiotics and probiotics) have the capacity to reverse pathologic changes in gut flora and local immunity. Intestinal health and disease need to be thoroughly characterized to understand the interplay between the indigenous microbiota, the immune system and genetic host factors. This Review provides a broad overview of the importance of the intestinal microbiota in chronic disorders of the gut.     

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.     

Rationale for probiotic and antibiotic treatment strategies in inflammatory bowel diseases

Inflammatory bowel diseases (IBD), commonly referred to as Crohn's disease and ulcerative colitis are chronic aggressive disorders which share many similarities concerning pathomechanism and clinical course, but have very distinct features. Both entities are mainly located in areas with high bacterial concentrations, such as the terminal ileum and cecum in Crohn's disease and the rectum in ulcerative colitis. In recent years, overwhelming evidence accumulated, supporting the hypothesis that IBD are characterized by a genetically determined, overly aggressive immune response towards ubiquitous luminal antigens, especially commensal bacteria and their products. Trials in both human IBD and experimental colitis have demonstrated that broad-spectrum antibiotics may influence the course of ulcerative colitis and Crohn's disease and antibiotics with narrow activity against the anaerobic fraction of the flora can prevent relapse in Crohn's disease after surgically induced remission. Since relevant antibiotic strategies can be associated with some side effects, the ongoing research recently focused on alternative methods to modify the intestinal flora in patients with IBD. Clinical observations including few controlled trials, basic research, and animal studies have suggested a potential role for probiotic bacteria within the treatment regimens for IBD. However, the mode of action of these organisms is still largely unclear and in vitro studies are inconclusive. This review summarizes recent in vitro and in vivo data regarding the role of the intestinal microflora in the pathogenesis of chronic intestinal inflammation and possible therapeutic mechanisms of probiotic bacteria relevant to IBD. Furthermore, we will review clinical trials examining the efficacy of antibiotic and probiotic treatment strategies in IBD.     

西方国家与我国炎症性肠病的过去、现在和将来

20世纪以来,炎症性肠病(IBD)的发病率呈持续上升趋势,其病因尚未完全阐明,目前普遍的观点认为,肠道菌群在遗传易感者肠道启动了持续的免疫和炎症反应。本文就过去对IBD的描述、现在对IBD发病机制的重要发现和治疗以及将来对IBD研究的设想作一概述。     

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.