Using probiotics and prebiotics to improve gut health

Recent molecular-based investigations have confirmed the species diversity and metabolic complexity of the human gut microbiota. It is also increasingly clear that the human gut microbiota plays a crucial role in host health, both as a source of infection and environmental insult and, conversely, in protection against disease and maintenance of gut function. Although little is known about the health impact of the dominant groups of gut bacteria it is generally accepted that bifidobacteria and lactobacilli are important components of what might be termed the beneficial gut microbiota. The microbiota management tools of probiotics, prebiotics and synbiotics have been developed and, indeed, commercialized over the past few decades with the expressed purpose of increasing numbers of bifidobacteria and/or lactobacilli within the gastrointestinal tract.     

Bifidobacteria and lactobacilli in human health

The gastrointestinal microflora is a complex ecological system, normally characterized by a flexible equilibrium. The most important role of the microflora, from the point of view of the host, is probably to act in colonization resistance against exogenous, potentially pathogenic, microorganisms. Bifidobacteria and lactobacilli are Gram-positive lactic acid-producing bacteria constituting a major part of the intestinal microflora in humans and other mammals. Administration of antimicrobial agents may cause disturbances in the ecological balance of the gastrointestinal microflora with several unwanted effects such as colonization by potential pathogens. To maintain or reestablish the balance in the flora, supplements of intestinal microorganisms, mainly bifidobacteria and lactobacilli, sometimes called probiotics, have been successfully used. This article reviews the role of bifidobacteria and lactobacilli in human health.     

Enhanced delivery of bifidobacteria and fecal changes after multiple oral administrations of bifidobacteria-loaded alginate poly-l-lysine microparticles in human volunteers

Enhanced delivery of bifidobacteria and fecal changes were compared following multiple oral administrations of protected bifidobacteria-loaded alginate poly-l-lysine microparticles (bap-microparticles) and unprotected bifidobacteria cultures over a period of 1 month to healthy human volunteers as preliminary in vivo studies. When bap-microparticles were orally administered, enhanced delivery of bifidobacteria was achieved. The viability of the bifidobacteria was significantly increased approximately 11.5-30 times (1.06-1.48 log cycles) during the ingestion period when compared with the bifidobacteria culture group (p < 0.05). However, other gut microflora such as bifidobacteria, enterobacteriaceae, lactic acid bacteria, and staphylococci in feces were not significantly different between the two groups. Encapsulated bifidobacteria resulted in more frequent defecation and decreased fecal viscosity.     

Probiotics and prebiotics in inflammatory bowel disease: microflora 'on the scope'

The intestinal microflora is a large bacterial community that colonizes the gut, with a metabolic activity equal to an organ and various functions that affect the physiology and pathology of the host's mucosal immune system. Intestinal bacteria are useful in promotion of human health, but certain components of microflora, in genetically susceptible individuals, contribute to various pathological disorders, including inflammatory bowel disease. Clinical and experimental observations indicate an imbalance in protective and harmful microflora components in these disorders. Manipulation of gut flora to enhance its protective and beneficial role represents a promising field of new therapeutic strategies of inflammatory bowel disease. In this review, we discuss the implication of gut flora in the intestinal inflammation that justifies the role of probiotics and prebiotics in the prevention and treatment of inflammatory bowel disease and we address the evidence for therapeutic benefits from their use in experimental models of colitis and clinical trials.     

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.     

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.     

Impact of cefbuperazone on the colonic microflora in patients undergoing colorectal surgery

Cefbuperazone was given intravenously in a dose of 1 g at induction of anaesthesia, followed by a subsequent dose of 1 g 12 h after the first dose, to 10 patients undergoing colorectal surgery. A series of serum and faecal specimens were taken for analysis of cefbuperazone concentrations. Tissue samples from the gut wall were taken at surgery. The maximum serum concentrations (mean value 98.6 +/- 9.1 mg/l) during surgery were reached 30 min after cefbuperazone administration. The cefbuperazone concentration in the tissue samples varied between 7.3 and 40.5 mg/kg and the concentration in the faecal samples between 0 and 27.0 mg/kg. Faecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. The aerobic bacteria--streptococci, enterococci and enterobacteria--were suppressed significantly during the prophylaxis period. Among the anaerobic bacteria, cocci, bifidobacteria, eubacteria, lactobacilli, clostridia, fusobacteria and bacteroides decreased markedly during the same period. After four weeks the microflora was normalized in all patients. No postoperative infections occurred.     

炎症性肠疾病的微生态调节治疗

炎症性肠病包括溃疡性结肠炎、克罗恩病等,表现为肠黏膜免疫系统对肠内共生细菌产生异常反应的一类慢性肠道疾病,有明显家族聚集性但病因不明,肠道与其共栖微生物的稳态平衡一旦破坏即可发病。不同遗传个体对有害菌、无害菌或益生菌等肠内共生菌呈现不同的反应性,而肠内共生菌对肠道卫生以及天然免疫和获得免疫间的互动具有重要作用。     

The place of probiotics in human intestinal infections

A number of studies have been carried out on the effect of several probiotic species on treatment and prevention of intestinal infections. The most commonly used microorganisms are lactic-acid producing bacteria such as lactobacilli and bifidobacteria belonging to the human normal microflora. In vitro and animal studies have shown that probiotic microorganisms interfere with the colonisation of Helicobacter pylori and of enteropathogenic microorganisms. In humans the significance is more uncertain. Clinically significant benefits of probiotics have been demonstrated in the treatment of rotavirus induced diarrhoea and of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea (AAD). In patients suffering from inflammatory bowel disease, several probiotic strains have been shown to be as effective as traditional medication in preventing relapses. Standardised and well performed studies are needed to elucidate further the mechanisms of action and the clinical significance of probiotics.     

Enhanced Delivery of Bifidobacteria and Fecal Changes after Multiple Oral Administrations of Bifidobacteria-loaded Alginate Poly-l-lysine Microparticles in Human Volunteers

Enhanced delivery of bifidobacteria and fecal changes were compared following multiple oral administrations of protected bifidobacteria-loaded alginate poly-l-lysine microparticles (bap-microparticles) and unprotected bifidobacteria cultures over a period of 1 month to healthy human volunteers as preliminary in vivo studies. When bap-microparticles were orally administered, enhanced delivery of bifidobacteria was achieved. The viability of the bifidobacteria was significantly increased ～ 11.5–30 times (1.06–1.48 log cycles) during the ingestion period when compared with the bifidobacteria culture group (p < 0.05). However, other gut microflora such as bifidobacteria, enterobacteriaceae, lactic acid bacteria, and staphylococci in feces were not significantly different between the two groups. Encapsulated bifidobacteria resulted in more frequent defecation and decreased fecal viscosity.     

Inhibitory effects ofBifidobacterium Spp. isolated from a healthy korean on harmful enzymes of human intestinal microflora

Five hundreds of bifidobacteria were isolated from a healthy Korean and the inhibitory effects of these isloated bacteria on harmful enzymes of human intestinal microflora were examined by cocultivation of the isolated bifidobacteria withE. coli or total human intestinal microflora. In comparison with the results ofE. coli or intestinal microflora cultivation,Bifidobacterium breve K-110,B. breve K-111 andB. infantis K-525 effectively inhibited harmful enzymes (β-glucuronidase and tryptophanase) of f.coli and lowered the pH of the culture media. Also they inhibited the harmful enzymes (β-glucosidase, β-glucuronidase, tryptophanase and urease) and ammonia production of intestinal microflora, and lowered pH of the culture media by increasing lactic acid bacteria of intestinal microflora. When these isolated bifidobacteria were administered on mice, fecal harmful enzymes were also inhibited. Among tested bifidobacteria,B. breve K-110 had the highest inhibitory effect of fecal harmful enzymes.     

Effect of red pepper Capsicum annuum var. conoides and garlic Allium sativum on plasma lipid levels and cecal microflora in mice fed beef tallow.

Antihyperlipidemia or hypocholesterolaemic and antibacterial activities of red hot pepper and garlic are well known. To determine the effect of the dietary spices ingested to suppress blood lipids on the intestinal condition, we examined plasma lipid levels and cecal microflora in mice that were fed diets containing 19% (w/w) beef tallow and 2% red pepper Capsicum annuum var. conoides 'Takanotume' (RP) or garlic Allium sativum 'White' (GP) for 4-weeks. Plasma triacylglyceride level was suppressed by the spices. RP lowered cecal bacteroidaceae, a predominant bacterial group (from 9.4 to 9.0 log CFU/g), bifidobacteria (from 8.7 to 7.6 log CFU/g), and staphylococci. Although GP increased the cecal weight including their contents, significant differences were not shown in the cecal microflora. These results suggest that RP can affect the intestinal condition and host health through the disturbance of intestinal microflora.     

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.     

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.     

益生菌益生元复合制剂对头孢曲松引起的肠道菌群及免疫异常改善效果的研究

摘要：目的 探究由乳双歧杆菌HN019、乳双歧杆菌V9与益生元共同组成的益生菌、益生元复合制剂对头孢曲松引起的 小鼠免疫异常以及肠道菌群失调的改善效果。方法 45只四周龄雄性Balb/c小鼠随机分为3组,分别灌胃生理盐水、头孢曲松以 及头孢曲松+益生菌复合制剂30d后,检测受试小鼠的体重、逆转录实时荧光定量PCR(RT-qPCR)分析脾脏细胞中免疫細胞因子的 mRNA表达、用RT-qPCR和高通量测序技術检测粪便双歧杆菌含量以及粪便细菌的构成。结果 头孢曲松+复合制剂组受试小鼠 体重显著低于空白组(P<0.05)。头孢曲松组脾脏IL-10 mRNA表达量有下降趋势,头孢曲松+益生菌复合制剂组受试小鼠脾脏IL- 10 mRNA表达量显著高于头孢曲松组(P<0.05)。头孢曲松组受试小鼠粪便双歧杆菌含量有下降趋势,头孢曲松+益生菌复合制剂 组受试小鼠粪便双歧杆菌含量显著高于头孢曲松组(P<0.05)。头孢曲松组和头孢曲松+复合制剂组与空白组相比,受试小鼠α-多 样性有不同程度的降低。头孢曲松组拟杆菌门减少,厚壁菌门和肠球菌属增多。头孢曲松+复合制剂组与头孢曲松组相比,受 试小鼠厚壁菌门与肠球菌属的相对丰度减少,放线菌门增加。结论 头孢曲松可导致宿主免疫功能异常,肠道双歧杆菌等有益 菌减少,肠道菌群整体结构紊乱。益生菌、益生元复合制剂可通过促进抗炎因子的产生改善了宿主免疫功能,并通过增加双歧 杆菌和减少某些致病菌在一定程度上改善了头孢曲松导致的宿主肠道菌群异常、促进肠道健康。     

常见药物毒性相关的肠道菌群研究进展

肠道菌群在物质信息传递、代谢等方面发挥重要作用，随着生物技术的进步，人们对肠道菌群与宿主健康的关系有了进一步的认识。近年来的研究发现，肠道菌群与某些药物毒性存在相关性。文章总结了药物肝毒性、肾毒性、神经毒性和生殖及幼龄毒性相关的肠道菌群研究成果，以期为药物毒理研究提供参考。     

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.     

Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats

Splenda is comprised of the high-potency artificial sweetener sucralose (1.1%) and the fillers maltodextrin and glucose. Splenda was administered by oral gavage at 100, 300, 500, or 1000 mg/kg to male Sprague-Dawley rats for 12-wk, during which fecal samples were collected weekly for bacterial analysis and measurement of fecal pH. After 12-wk, half of the animals from each treatment group were sacrificed to determine the intestinal expression of the membrane efflux transporter P-glycoprotein (P-gp) and the cytochrome P-450 (CYP) metabolism system by Western blot. The remaining animals were allowed to recover for an additional 12-wk, and further assessments of fecal microflora, fecal pH, and expression of P-gp and CYP were determined. At the end of the 12-wk treatment period, the numbers of total anaerobes, bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria were significantly decreased; however, there was no significant treatment effect on enterobacteria. Splenda also increased fecal pH and enhanced the expression of P-gp by 2.43-fold, CYP3A4 by 2.51-fold, and CYP2D1 by 3.49-fold. Following the 12-wk recovery period, only the total anaerobes and bifidobacteria remained significantly depressed, whereas pH values, P-gp, and CYP3A4 and CYP2D1 remained elevated. These changes occurred at Splenda dosages that contained sucralose at 1.1-11 mg/kg (the US FDA Acceptable Daily Intake for sucralose is 5 mg/kg). Evidence indicates that a 12-wk administration of Splenda exerted numerous adverse effects, including (1) reduction in beneficial fecal microflora, (2) increased fecal pH, and (3) enhanced expression levels of P-gp, CYP3A4, and CYP2D1, which are known to limit the bioavailability of orally administered drugs.     

Probiotics and immune regulation of inflammatory bowel diseases

Intestinal microflora play an important role in the pathogenesis of inflammatory bowel diseases (IBD). Certain probiotic bacteria provide beneficial effects for human health and intervention of IBD. Possible mechanisms underlying these effects are diverse and include many aspects of the interaction of the host with its commensal microflora, with immunological and non-immunological effects. This review paper will focus on the recent progress in the use of probiotics in the treatment of IBD, and discuss the potential immunological mechanisms underlying their effects, such as the modulation of mucosal T cell, B cell, epithelial cell, dendrtic cell, macrophage, nature killer cell, antibody, and cytokine responses.     

Probiotics: potential pharmaceutical applications.

Realisation of the importance of human gut microbiota in health restoration and maintenance has kindled an interest in probiotics. Probiotics are defined as the microbial food supplements, which beneficially affect the host by improving its intestinal microbial balance. Probiotics are the health enhancing functional food ingredients used therapeutically to prevent diarrhea, improve lactose tolerance and modulate immunity. They may also have potential to prevent cancer and lower serum cholesterol levels. Lactobacillus, Bifidobacterium and several other microbial species are perceived to exert such effects by changing the composition of the gut microbiota. However, it is important that exogenously administered bacteria reach and establish themselves in the large intestine in an intact form. The use of non-digestible oligosaccharides ('prebiotics') can fortify intestinal microflora and stimulate their growth. The present review encompasses information regarding the probiotics and their proposed uses. It addresses the concepts of prebiotics and synbiotics, the application of genetic engineering to produce newer probiotics. Finally, the list of commercially available products are reviewed with discussion of questions regarding the reliability, utility and the safety of these products.