Probiotics and prebiotics — renaissance of a therapeutic principle

Probiotics are nonpathogenic microorganisms mostly of human origin which, when administered in adequate amounts, confer a health benefit on the host and enable to prevent or improve some diseases. Probiotics may be a natural temporary constituent of the resident intestinal microflora, but their concentration is not sufficient for therapeutic purposes. The microbiota, the intestinal epithelium, and the mucosal immune system constitute the gastrointestinal ecosystem. All three components are essential for complete functional and developmental maturity of the system. The viability of intestinal microflora (including probiotic strains) requires the availability of nutritional substrates (prebiotics), i.e. various types of fiber and oligosaccharides. Prebiotics are cleaved by microbial enzymes to numerous substances (short-chain fatty acids, aminoacids, polyamines, growth factors, vitamins and antioxidants) indispensable for metabolic and functional activities of the intestinal mucosa. The principal probiotics in use include lactobacilli, bifidobacteria, some nonpathogenic strains of Escherichia coli, and Saccharomyces boulardii. These microbiota display favourable effects which qualify them for therapeutic use. For this purpose, probiotics have to fulfill a series of requirements verifying their efficacy and safety. Experimental and clinical studies examine the prerequisites for the administration of probiotics in digestive diseases, allergic and atopic affections, as well as in some extraintestinal conditions. Future goals of probiotic application include genomic analysis, controlled postnatal colonisation of the digestive tract, the use of probiotics as carriers of peroral vaccines, and recombinant probiotics with in-situ production and targeted application of therapeutic molecules.     

肠道菌群对高血压的作用

肠道微生物对机体的健康起重要作用,肠道菌群失调不仅引起胃肠道疾病,还对包括高血压在内的心血管疾病等造成影响。研究表明,用益生菌或其发酵产品干预后,可以调节肠道微生态,高血压状态也得以改善。关于益生菌降压的机制,有产生肽类等降压物质,改善血管氧化和炎症水平,短链脂肪酸的作用,肠道菌群与神经系统相互作用等。深入研究肠道菌群与高血压的关系,为高血压的营养治疗提供了一种新途径。     

The role of probiotics on each component of the metabolic syndrome and other cardiovascular risks

Introduction: Probiotics are defined as live microorganisms that when administered in adequate amounts confer health benefits to the host. The consumption of probiotics has gained increasing recognition from the scientific community due to the promising effects on metabolic health through gut microbiota modulation.

Areas covered: This article presents a review of scientific studies investigating probiotic species and their effects on different risk factors of the metabolic syndrome (MetS). This article also presents a summary of the major mechanisms involved with gut microbiota and the components of the MetS and raises the key issues to be considered by scientists in search of probiotics species for treatment of patients suffering from this metabolic disorder.

Expert opinion: Probiotics may confer numerous health benefits to the host through positive gut microbiota modulation. The strain selection is the most important factor for determining health effects. Further studies may consider gut microbiota as a novel target for prevention and management of MetS components and other cardiovascular risks.     

Microecology as a target for therapeutic intervention in inflammatory bowel disease

The gastrointestinal tract is populated by several hundred grams of bacteria. Recognition of the symbiosis between bacteria and host is drawing particular attention to the implications of bacteria in human health. Probiotics are living microorganisms that upon ingestion in certain numbers exert health benefits. Prebiotics are non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth or activity of a limited number of gut bacteria. In inflammatory bowel disease (IBD), the gut flora is the key factor driving the inflammatory process that leads to intestinal lesions. Interaction of certain commensal bacteria with the gut mucosa triggers mucosal inflammation. However, certain probiotic strains are able to downregulate inflammatory pathways. Restoring the microbial balance with prebiotics and probiotics offers promise for the control of IBD.     

Benefaction of probiotics for human health: A review

Humans are a unique reservoir of heterogeneous and vivacious group of microbes, which together forms the human-microbiome superorganism. Human gut serves as a home to over 100–1000 microbial species, which primarily modulate the host internal environment and thereby, play a major role in host health. This spectacular symbiotic relationship has attracted extensive research in this field. More specifically, these organisms play key roles in defense function, eupepsia along with catabolism and anabolism, and impact brain-gut responses. The emergence of microbiota with resistance and tolerance to existing conventional drugs and antibiotics has decreased the drug efficacies. Furthermore, the modern biotechnology mediated nano-encapsulated multiplex supplements appear to be high cost and inconvenient. Henceforth, a simple, low-cost, receptive and intrinsic approach to achieve health benefits is vital in the present era. Supplementation with probiotics, prebiotics, and synbiotics has shown promising results against various enteric pathogens due to their unique ability to compete with pathogenic microbiota for adhesion sites, to alienate pathogens or to stimulate, modulate and regulate the host's immune response by initiating the activation of specific genes in and outside the host intestinal tract. Probiotics have also been shown to regulate fat storage and stimulate intestinal angiogenesis. Hence, this study aims to underline the possible beneficial impact of probiotics for human health and medical sectors and for better lifestyle.     

益生菌的肠道保健机制

益生菌是一类重要的微生物调节剂,对肠道健康具有极其重要的促进作用。益生菌不仅能调节肠道菌群环境、提供能量,还能激活肠道自身体液免疫与细胞免疫系统,达到保护机体的目的。本文论述了益生菌对肠道的保健作用机制。     

A Healthy Gut for a Healthy Brain: Preclinical,Clinical and Regulatory Aspects

A large body of research has shown the presence of a complex pathway of communications between the gut and the brain. It is now recognized that, through this pathway, the microbiota can influence brain homeostasis and plasticity under normal and pathological conditions.This review aims at providing an overview of preclinical and clinical pieces of evidence supporting the possible role of gut-brain axis modulation in physiological aging, in a neurodevelopmental disorder, the autism spectrum disorders and in a substance abuse disorder, the alcohol addiction.Since the normalization of gut flora can prevent changes in the behavior, we postulate that the gut-brain axis might represent a possible target for pharmacological and dietary strategies aimed at improving not only intestinal but also mental health. The present review also reports some regulatory considerations regarding the use of probiotics, illustrating the most debated issues about the possibility of considering probiotics not only as a food supplement but also as a “full” medicinal product.     

Probiotics in inflammatory bowel disease--therapeutic rationale and role

The intestinal flora has a conditioning effect on intestinal homeostasis, delivering regulatory signals to the epithelium, the mucosal immune system and to the neuromuscular activity of the gut. Beneficial metabolic activities of the enteric flora include nutrient production, metabolism of dietary carcinogens, conversion of prodrugs to active drugs. However, increasing evidence suggests that some components of the enteric flora are essential ingredients in the pathogenesis of inflammatory bowel disease (IBD); this has prompted interest in therapeutic manipulation of the flora with probiotics. Probiotics are biologic control agents-described as live microbial food supplements which confer a health benefit beyond inherent basic nutrition. Multiple potential beneficial effects have been attributed to the probiotic use of lactic acid bacteria, bifidobacteria and other non-pathogenic commensals. At present, much of the promise of probiotics remains outside the realm of evidence-based medicine and awaits the results of prospective trials, now underway. No reliable in vitro predictors of in vivo efficacy of putative probiotics have been identified. Rigorous comparisons of probiotic performance have not been performed and the suitability of a given probiotic for different individuals is largely unexplored. Notwithstanding, an improved understanding of the normal commensal flora and host-flora interactions has the potential to open up new therapeutic strategies for inflammatory disorders of the gut.     

Probiotics: Isolated bacteria strain or mixtures of different strains? Two different approaches in the use of probiotics as therapeutics

Probiotics are cultures of beneficial bacteria from the healthy gut microflora that improve the balance of the intestinal milieu by modifying the intestinal microflora and suppressing enhanced inflammatory responses. Probiotics are currently the subject of intense and widespread research as functional foods since they are known to induce health benefits, may be used as pharmaceutical preparations, and have achieved a "generally recognized as safe" (GRAS) status. Lactobacillus strains can also be genetically engineered for use in oral immunotherapeutic applications, such as vaccination and delivery of immunoregulatory substances. In the present review we evaluate the two different approaches to the therapeutic use of probiotics. We also focus on recent findings in the field of molecular biology and genetics of the intestinal immune response related to the microflora and intestinal ecology, in order to understand the mechanisms of action of probiotics and their present indications in gastrointestinal diseases. Finally, with a view to future perspectives we provide some examples of probiotics that are being assessed and have great potential in improving the health of animals and man.     

益生菌治疗自身免疫病的研究进展

益生菌是一类活的非致病性微生物,大量摄入能够使人体肠道菌群正常化,并对健康有潜在益处。自身免疫病是一类由于自身免疫耐受被打破而导致器官组织损害的慢性炎症性疾病,包括常见的类风湿性关节炎、系统性红斑狼疮、多发性硬化等,其发病率呈逐年上升趋势,已有研究证实其发生与菌群失调有关,传统的自身免疫病治疗药物常引发较严重的不良反应,使得疗效受限。益生菌已被证实对多种疾病的治疗具有潜在益处,且具有菌株特异性,探究益生菌用于治疗自身免疫病是目前一大焦点,对此方面的研究进展进行综述,旨在为临床选择治疗方案提供理论支持。     

Interactions of gut microbiota with functional food components and nutraceuticals

The human gut is populated by an array of bacterial species, which develop important metabolic and immune functions, with a marked effect on the nutritional and health status of the host. Dietary component also play beneficial roles beyond basic nutrition, leading to the development of the functional food concept and nutraceuticals. Prebiotics, polyunsaturated fatty acids (PUFAs) and phytochemicals are the most well characterized dietary bioactive compounds. The beneficial effects of prebiotics mainly relay on their influence on the gut microbiota composition and their ability to generate fermentation products (short-chain fatty acids) with diverse biological roles. PUFAs include the ω-3 and ω-6 fatty acids, whose balance may influence diverse aspects of immunity and metabolism. Moreover, interactions between PUFAs and components of the gut microbiota may also influence their biological roles. Phytochemicals are bioactive non-nutrient plant compounds, which have raised interest because of their potential effects as antioxidants, antiestrogenics, anti-inflammatory, immunomodulatory, and anticarcinogenics. However, the bioavailability and effects of polyphenols greatly depend on their transformation by components of the gut microbiota. Phytochemicals and their metabolic products may also inhibit pathogenic bacteria while stimulate the growth of beneficial bacteria, exerting prebiotic-like effects. Therefore, the intestinal microbiota is both a target for nutritional intervention and a factor influencing the biological activity of other food compounds acquired orally. This review focuses on the reciprocal interactions between the gut microbiota and functional food components, and the consequences of these interactions on human health.     

Modification of intestinal flora in the treatment of inflammatory bowel disease

Because the intestinal microflora play an important role in the development of inflammatory bowel disease (IBD), there is currently some interest in the manipulation of the composition of the microflora towards a potentially more remedial community. This review summarizes the clinical and experimental efficacy of the manipulation of microflora by the use of prebiotics, probiotics, synbiotics, and antibiotics in IBD. Prebiotics, defined as nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth or activity of one or a limited number of bacterial species already resident in the colon, can modulate the colonic microbiota by increasing the number of specific bacteria and thus changing the composition of the microbiota. Prebiotics for IBD include lactosucrose, oligofructose, inulin, bran, psyllium, and germinated barley foodstuff (GBF). GBF, which mainly consists of dietary fiber and glutamine-rich protein, is a prebiotic foodstuff for ulcerative colitis. GBF has shown to be converted into a preferential nutrient for colonocytes through Eubacterium and Bifidobacterium and also inactivate nuclear factor kappa B (NFkB). Moreover, it exhibits a potent water-holding capacity and bile-acid binding capacity. Probiotics, which are microbial food supplements that beneficially affect the host by improving the intestinal microbial balance, have been used to change the composition of colonic microbiota. The approaches for IBD include VSL#3, Nissle1917, Clostridium butyricum and Bifidobacterium-fermented milk. Use of Lactococci secreting IL-10 provides excellent results. The combination of prebiotics and probiotics in a synbiotic has not been studied in IBD but is promising. The use of antibiotics continues to be of interest. Although these strategies hold great promise and appear to be useful in some settings, more clinical study is needed to firmly establish the relevance of these therapies.     

Gut microbiota: a potential new territory for drug targeting

The significant involvement of the gut microbiota in human health and disease suggests that manipulation of commensal microbial composition through combinations of antibiotics, probiotics and prebiotics could be a novel therapeutic approach. A systems perspective is needed to help understand the complex host-bacteria interactions and their association with pathophysiological phenotypes so that alterations in the composition of the gut microbiota in disease states can be reversed. In this article, we describe the therapeutic rationale and potential for targeting the gut microbiota, and discuss strategies and systems-oriented technologies for achieving this goal.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Review article: prebiotics in the gastrointestinal tract

BACKGROUND: Prebiotics are short-chain carbohydrates that alter the composition, or metabolism, of the gut microbiota in a beneficial manner. It is therefore expected that prebiotics will improve health in a way similar to probiotics, whilst at the same time being cheaper, and carrying less risk and being easier to incorporate into the diet than probiotics. AIM: To review published evidence for prebiotic effects on gut function and human health. METHODS: We searched the Science Citation Index with the terms prebiotic, microbiota, gut bacteria, large intestine, mucosa, bowel habit, constipation, diarrhoea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, calcium and cancer, focussing principally on studies in humans and reports in the English language. Search of the Cochrane Library did not identify any clinical study or meta-analysis on this topic. RESULTS: Three prebiotics, oligofructose, galacto-oligosaccharides and lactulose, clearly alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus numbers. These carbohydrates are fermented and give rise to short-chain fatty acid and intestinal gas; however, effects on bowel habit are relatively small. Randomized-controlled trials of their effect in a clinical context are few, although animal studies show anti-inflammatory effects in inflammatory bowel disease, while calcium absorption is increased. CONCLUSIONS: It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.     

Review article: probiotics and prebiotics in irritable bowel syndrome

Background  The human gut harbours a complex community of bacteria whose relationship with their host is normally mutually beneficial. Recent studies suggest a disturbance of this relationship in irritable bowel syndrome (IBS) and the potential to correct this using prebiotics and probiotics.
Aim  To review the mechanisms of action of probiotics and prebiotics in IBS and to assess their performance in clinical trials.
Methods  Articles relating to modes of action and randomized control trials of treatment were reviewed by searching PubMed using terms 'probiotic', 'prebiotic' and 'irritable bowel'. Small uncontrolled studies in IBS were excluded.
Results  Probiotics can enhance gut barrier function, inhibit pathogen binding and modulate gut inflammatory response. They can also reduce visceral hypersensitivity associated with both inflammation and psychological stress. Probiotics can alter colonic fermentation and stabilize the colonic microbiota. Several large randomized, placebo-controlled trials of adequate design have shown an improvement in flatulence and abdominal distension with a reduction in composite IBS symptoms scores.
Conclusions  Each probiotic has unique features and IBS patients are heterogeneous. Future efforts should be directed to identifying biomarkers of responsiveness to facilitate better targeting of treatment and hence improved efficacy.     

Metabolic endotoxemia and cardiovascular disease: A systematic review about potential roles of prebiotics and probiotics

Translocation of microbiome-derived lipopolysaccharide (LPS) to the bloodstream (metabolic endotoxaemia) is associated with a significantly increased risk of cardiovascular diseases (CVD); however, the direction of this association is not fully understood. It has been revealed by some studies that alterations in the intestinal microbiota (dysbiosis) lead to increased intestinal permeability and translocation of LPS to the blood circulation. LPS may trigger toll-like receptor 4- (TLR-4) mediated inflammatory responses; this could lead to a chronic low-grade pro-inflammatory condition named metabolic endotoxaemia (ME), which is typically observed in CVD patients. ME is promoted by increased intestinal permeability. Moreover, dysbiosis leads to production of trimethylamine-N-oxide (TMAO), a gut bacterial metabolite suggested as a new risk factor in CVD development. Probiotics, extensively reviewed for decades, are live microorganisms which, when taken in adequate amounts, have beneficial effects on the host metabolism. Prebiotics are a type of dietary fibre that act as nourishment for the good bacteria in the gut and decrease the population of pathogen bacteria that produce greater amounts of endotoxins. Although an association has been postulated between ME and CVD, the results of studies investigating the role of antibiotic therapy in preventing the disease have been inconsistent. In this review, we discuss how prebiotics and probiotics modulate gut microbiota and consequently might help with prevention and/or treatment of CVD associated with ME.     

Probiotics: "living drugs".

The uses, mechanisms of action, and safety of probiotics are discussed. Probiotics are live microorganisms or microbial mixtures administered to improve the patient's microbial balance, particularly the environment of the gastrointestinal tract and the vagina. The yeast Saccharomyces boulardii and the bacterium Lactobacillus rhamnosus, strain GG, have shown efficacy in clinical trials for the prevention of antimicrobial-associated diarrhea. Other probiotics that have demonstrated at least some promise as prophylaxis for this type of diarrhea are Lactobacillus acidophilus, Bifidobacterium longum, and Enterococcus faecium. The use of S. boulardii as an adjunctive treatment to therapy with metronidazole or vancomycin has been found in controlled studies to decrease further recurrences of Clostridium difficile-associated disease. Other gastrointestinal disorders for which probiotics have been studied include traveler's diarrhea, acute infantile diarrhea, and acute diarrhea in adults. Several Lactobacillus species given in yogurt or in tablet or suppository form have shown clinical efficacy as a treatment for vaginal infections. Lactobacillus strains have also been examined as a treatment for urinary-tract infections. Putative mechanisms of action of probiotics include production of pathogen-inhibitory substances, inhibition of pathogen attachment, inhibition of the action of microbial toxins, stimulation of immunoglobulin A, and trophic effects on intestinal mucosa. The available probiotics are considered nonpathogenic, but even benign microorganisms can be infective when a patient is severely debilitated or immunosuppressed. Probiotics have demonstrated an ability to prevent and treat some infections. Effective use of probiotics could decrease patients' exposure to antimicrobials. Additional controlled studies are needed to clearly define the safety and efficacy of these agents.     

Next generation probiotics in disease amelioration

Studies on the role of gut commensal bacteria in health development have rapidly attracted much more attention beyond the classical pathogens over the last decade. Many important reports have highlighted the changes in the gut microbiota (dysbiosis) are closely related to development of intra- and extra-intestinal, chronic inflammation related diseases such as colitis, obesity/metabolic syndromes, diabetes mellitus, liver diseases, cardiovascular diseases and also cancer and neurodegenerative diseases. To circumvent these difficulties, the strategy of modulating the structure of the gut microbiota has been under intensive study and shed more light on amelioration of these inflammation related diseases. While traditional probiotics generally show marginal ameliorative effects, emerging next generation probiotics start to reveal as new preventive and therapeutic tools. Recent studies have unraveled many potential next generation probiotics (NGP). These include Prevotella copri and Christensenella minuta that control insulin resistance, Parabacteroides goldsteinii, Akkermansia muciniphila and Bacteroides thetaiotaomicron that reverse obesity and insulin resistance, Faecalibacterium prausnitzii that protects mice against intestinal diseases, and Bacteroides fragilis that reduces inflammation and shows anticancer effect. New agents will soon be revealed for targeted therapy on specific inflammation related diseases. The important roles of next generation probiotics and gut microbiota normobiosis on the maintenance of intestinal integrity and homeostasis are emphasized.