A potential role of probiotics in colorectal cancer prevention: review of possible mechanisms of action

A number of investigations, mainly using in vitro and animal models, have demonstrated a wide range of possible mechanisms, by which probiotics may play a role in colorectal cancer (CRC) prevention. In this context, the most well studied probiotics are certain strains from the genera of lactobacilli and bifidobacteria. The reported anti-CRC mechanisms of probiotics encompass intraluminal, systemic, and direct effects on intestinal mucosa. Intraluminal effects detailed in this review include competitive exclusion of pathogenic intestinal flora, alteration of intestinal microflora enzyme activity, reduction of carcinogenic secondary bile acids, binding of carcinogens and mutagens, and increasing short chain fatty acids production. Reduction of DNA damage and suppression of aberrant crypt foci formation have been well demonstrated as direct anti-CRC effects of probiotics on intestinal mucosa. Existing evidence clearly support a multifaceted immunomodulatory role of probiotics in CRC, particularly its ability to modulate intestinal inflammation, a well known risk factor for CRC. The effectiveness of probiotics in CRC prevention is dependent on the strain of the microorganism, while viability may not be a prerequisite for certain probiotic anticancer mechanisms, as indicated by several studies. Emerging data suggest synbiotic as a more effective approach than either prebiotics or probiotics alone. More in vivo especially human studies are warranted to further elucidate and confirm the potential role of probiotics (viable and non-viable), prebiotics and synbiotics in CRC chemoprevention.     

几种益生元制剂对肠道菌群作用效果的研究

目的探讨几种益生元制剂对肠道菌群作用效果。方法通过体外实验和体内试验。结果低聚果糖、水苏糖、低聚木糖、低聚异麦芽糖均能促进双歧杆菌和乳杆菌的增殖,并能够酸化肠道的pH;能够显著提高肠道的B／E值（肠道内双歧杆菌和肠杆菌数量log值的比值）,增加肠道中有益菌的比例,有益于稳定肠道的微生态平衡。结论这几种益生元制剂对肠道菌群有较好的调节作用。     

Human flora-associated (HFA) animals as a model for studying the role of intestinal flora in human health and disease

Although the intestinal flora in animals plays an important role in health and disease, there is little direct information regarding the role of the human intestinal flora. By inoculating germfree animals with human faeces, the major components of the human flora can be transferred into the ex-germfree animals, i.e. human flora-associated (HFA) animals. HFA animals therefore provide a stable model for studying the ecosystem and metabolism of the human intestinal flora. Results with HFA animals suggest the role of the human intestinal flora is somewhat different from the role of the animal flora in conventional experimental animals. Studies using HFA animals, therefore, will provide much needed information on the precise role of the intestinal flora in relation to humans. HFA animals also can be used as models to investigate the interactions between the human intestinal flora, host factors, dietary manipulations, and therapeutics, such as probiotics, prebiotics, and antibiotics.     

肠道菌群与肠易激综合征相关研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种功能性肠病,目前已有研究表明IBS的致病机制、症状的产生和持续时间可能与肠道菌群失调有关,且不同IBS亚型患者体内的肠道菌群种类有差异。IBS的发病机制尚不完全清楚,临床表现存在较大的个体差异。IBS的诊断和治疗尚未形成统一的标准。但已经有较多研究提示IBS可能与胃肠道动力、内脏高敏感性、肠道免疫反应和模式识别受体等密切相关,并且可以通过益生菌、益生元、抗生素、粪菌移植和饮食习惯等调节肠道菌群的失调,从而改善IBS的症状。这也为未来治疗IBS提供了新的思路。本文就肠道菌群的概况、IBS患者肠道菌群的特点、肠道菌群失衡导致IBS发病的可能机制以及IBS肠道菌群的相关治疗方法的研究进展作一综述。     

Prebiotic effect of fructo-oligosaccharides on the inner ear of DBA/2 J mice with early-onset progressive hearing loss

Nutrition and dietary habits contribute to the onset and progression of sensorineural hearing loss (SNHL). Fructo-oligosaccharides (FOS) are non-digestible oligosaccharides and are known as prebiotics, which enhance short-chain fatty acid (SCFA) production and antioxidant activity. Although a substantial number of studies have shown that FOS play a role in the prevention of lifestyle-related diseases as prebiotics, little is known about the effects on the inner ear. The purpose of this study is to investigate the effect of FOS on gene expression and spiral ganglion neuron (SGN) protection in the inner ear of DBA/2 J mice, which is a model for early-onset progressive hearing loss. DBA/2 J mice were fed either control diet or FOS diet contained 10% (w/w) of FOS for 8 weeks. Analysis of mice fed the FOS diet revealed a change in intestinal flora including an inversion of the ratio of Bacteroidetes and Firmicutes, which was followed by a significant increase in SCFAs in the cecum and a decrease in an oxidative stress marker in the serum. In the inner ear, gene expression of neurotrophin, brain-derived neurotrophic factor (BDNF), its receptor, tyrosine kinase receptor b (Trkb), and the SCFA receptor, free fatty acid receptor 3 (FFAR3), were increased by FOS. In addition, the survival rate of SGNs in the inner ear was maintained in FOS-fed mice. Altogether, these results suggest that a compositional variation of the intestinal flora due to a prebiotic effect may be involved in the progression of SNHL.     

Effects of the prebiotics inulin and lactulose on intestinal immunology and hematology of preruminant calves

Prebiotics are suggested as an alternative to antibiotics in animal rearing. Fermentable substances such as inulin or lactulose have been proposed to stimulate the immune system and health by modulation of the intestinal flora and its fermentation products. In this study, effects of inulin and lactulose on the intestinal health and hematology of calves have been investigated. Both prebiotics significantly decreased thrombocyte counts in peripheral blood. Only inulin was able to increase hemoglobin concentration and hematocrit. Total leukocyte count was decreased by lactulose while both prebiotics tended to lower monocyte proportions. mRNA expression of inflammation-related markers in the intestine was also affected by both prebiotics hinting at a decreased inflammatory status. This may be due to a possible decrease in intestinal pathogen load that remains to be verified. Only mRNA amounts of interleukin 8 were increased by lactulose in mesenteric lymph nodes. In the ileum, expression of a proliferation marker was increased by inulin while an apoptosis-related gene was increased by both prebiotics. The results of this study show a clear effect of prebiotics on certain parameters associated with animal health and performance that remain to be studied in detail in future investigations.     

The intestinal microbiome associated with lipid metabolism and obesity in humans and animals

Intestinal microbiota is considered to play an integral role in maintaining health of host by modulating several physiological functions including nutrition, metabolism and immunity. Accumulated data from human and animal studies indicate that intestinal microbes can affect lipid metabolism in host through various direct and indirect biological mechanisms. These mechanisms include the production of various signalling molecules by the intestinal microbiome, which exert a strong effect on lipid metabolism, bile secretion in the liver, reverse transport of cholesterol and energy expenditure and insulin sensitivity in peripheral tissues. This review discusses the findings of recent studies suggesting an emerging role of intestinal microbiota and its metabolites in regulating lipid metabolism and the association of intestinal microbiota with obesity. Additionally, we discuss the controversies and challenges in this research area. However, intestinal micro-organisms are also affected by some external factors, which in turn influence the regulation of microbial lipid metabolism. Therefore, we also discuss the effects of probiotics, prebiotics, diet structure, exercise and other factors on intestinal microbiological changes and lipid metabolism regulation.     

Prebiotics and calcium bioavailability

A prebiotic substance has been defined as a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon. Therefore, compared to probiotics, which introduce exogenous bacteria into the colonic microflora, a prebiotic aims at stimulating the growth of one or a limited number of the potentially health-promoting indigenous micro-organisms, thus modulating the composition of the natural ecosystem. In recent years, increasing attention has been focussed on the possible beneficial effects of prebiotics, such as enhanced resistance to invading pathogens, improved bowel function, anti-colon cancer properties, lipid lowering action, improved calcium bioavailability, amongst others. The objective of this review is to critically assess the available data on the effects of prebiotics on calcium bioavailability, and place it in the context of human physiology and, when possible, explain the underlying cellular and molecular mechanisms. The review will also try to highlight future areas of research that may help in the evaluation of prebiotics as potential ingredients for functional foods aimed at enhancing calcium bioavailability and protecting against osteoporosis.     

Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics

Most studies involving prebiotic oligosaccharides have been carried out using inulin and its fructo-oligosaccharide (FOS) derivatives, together with various forms of galacto-oligosaccharides (GOS). Although many intestinal bacteria are able to grow on these carbohydrates, most investigations have demonstrated that the growth of bifidobacteria, and to a lesser degree lactobacilli, is particularly favoured. Because of their safety, stability, organoleptic properties, resistance to digestion in the upper bowel and fermentability in the colon, as well as their abilities to promote the growth of beneficial bacteria in the gut, these prebiotics are being increasingly incorporated into the Western diet. Inulin-derived oligosaccharides and GOS are mildly laxative, but can result in flatulence and osmotic diarrhoea if taken in large amounts. However, their effects on large bowel habit are relatively minor. Although the literature dealing with the health significance of prebiotics is not as extensive as that concerning probiotics, considerable evidence has accrued showing that consumption of GOS and FOS can have significant health benefits, particularly in relation to their putative anti-cancer properties, influence on mineral absorption, lipid metabolism, and anti-inflammatory and other immune effects such as atopic disease. In many instances, prebiotics seem to be more effective when used as part of a synbiotic combination.     

Improvement of human faecal flora-associated mouse model for evaluation of the functional foods

AIMS: Animal models are required for evaluation of the functional foods such as pro/prebiotics exerting effects through the metabolism of the intestinal microflora. The object of this study was to establish new human flora-associated mice reflecting the environment of the human intestinal tract. METHODS AND RESULTS: We inoculated a human faecal suspension into segmented filamentous bacteria (SFB) monoassociated mice as a model system. In both human flora (HF) and SFB-associated mouse (HF-SFB mouse), intestinal characteristics such as the composition of intraepithelial lymphocytes, the expression of major histocompatibility complex (MHC) class II molecules and the number of immunoglobulin A-producing cells in the mucosa was closer to those of conventionally reared mice than was case with human flora-associated mice (HF mice) lacking SFB. Several predominant bacterial groups except lactobacilli in human flora were found in faeces of HF-SFB mice. Lactobacilli established small populations in the gut of HF-SFB mice when administered before inoculation with the human flora. Faecal enzymatic activities and organic acid concentration of HF-SFB mice proportionally reflected those of the donor subject. CONCLUSION: We established a new human flora-associated mouse (HF-SFB mouse), in which intestinal characteristics are normally developed and their major microbial composition reflect the human. SIGNIFICANCE AND IMPACT OF THE STUDY: HF-SFB mice are a valuable model for studying pro/prebiotic effects on the human intestine.     

Dysbacteriosis and preparations with probiotic function

Information on intestinal microecological disturbances (dysbacteriosis) and the preparations of probiotics, prebiotics and synbiotics used for the correction of resident normal colon microflora is presented. Probiotics are preparations containing live microbes or substances of microbial origin that, when introduced by natural methods are expected to confer beneficial physiologic, biochemical and immune effects to the host through the stabilization and the optimization of functions of normal microflora. Prebiotics are preparations containing a non-digestible food ingredient that beneficially affect the host by selectively stimulating the growth and the activity of a limited number of resident bacteria of normal microflora in the colon. Synbiotics are preparations obtained as the result of the rational combination of probiotics and prebiotics.     

The production of anorexigenic substances by intestinal flora

The role of intestinal flora in the production of anorexigenic substance was investigated. Proteus mirabilis (P. mirabilis) and Escherichia coli (E. coli) were found to produce an anorexigenic substance, while Enterococcus faecalis (E. faecalis, type 1 and 2) and Staphylococcus intermedius (S. intermedius) did not. The anorexigenic substance was purified and was detected as, a single though broad band by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The specific activity of the final form of the purified substance was 120 units/mg carbohydrate. The substance contained no protein residue and appeared to be a lipopolysaccharide. The evidence that intestinal flora produces an anorexigenic substance leads to an interesting assumption that the intestinal flora may be responsible for regulating food intake.     

Microbial treatment in chronic constipation

Chronic functional constipation is a kind of common intestinal disease that occurs in children, adults and elderly people. This disease not only causes great influence to physiological function, but also results in varying degrees of psychological barriers. At present, constipation treatments continue to rely on traditional methods such as purgative therapy and surgery. However, these approaches can disrupt intestinal function. Recent research between intestinal diseases and gut microbiota has gradually revealed a connection between constipation and intestinal flora disturbance, providing a theoretical basis for microbial treatment in chronic constipation. Microbial treatment mainly includes probiotic preparations such as probiotics, prebiotics, synbiotics and fecal microbiota transplantation (FMT). Due to its safety, convenience and curative effect, probiotic preparations have been widely accepted, especially gradually developed FMT with higher curative effects. Microbial treatment improves clinical symptoms, promotes the recovery of intestinal flora, and has no complications during the treatment process. Compared with traditional treatments, microbial treatment in chronic constipation has advantages, and is worthy of further promotion from clinical research to clinical application.     

Identification of Brassinosteroid-like Active Substances in Plant-cell Cultures

The effects of the flower lipid-saccharide complex and unsaponifiable matter (1g/kg of diet) from the sunflower on liver lipid metabolism and intestinal flora was studied in rats given cholesterol-enriched diets. After six weeks of feeding, the microsomal cholesterol concentration in the liver had been significantly reduced with the sunflower diet. The ratio of cholesterol/phospholipid was also reduced by the sunflower diet. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of the sunflower groups was significantly lower than that of the control group. There was no significant difference in the cholesterol 7α-hydroxylase activity, although this tended to increase with dietary sunflower consumption. The number of Bacillus in the cecum flora was significantly higher in the lipid-saccharide complex group than in the other groups, while Bifidobacterium and Eubacterium in the cecum flora was significantly higher in the unsaponifiable matter group when compared to the control group. These results suggest that the lipidsaccharide complex and unsaponifiable matter in the sunflower are related to liver cholesterol synthesis and intestinal flora.     

Pro- and prebiotics – the tasty guardian angels?

It is generally accepted that the bacterial community resident in the human intestinal tract has a major impact on gastrointestinal function and thereby on human health and well-being. Considerable efforts have been made to influence the intestinal microbiota by dietary means in such a way that the health of the host is beneficially affected. Pro- and prebiotics are food products that are specially designed for this purpose. Parallel to the increase in the acceptance of such products by the consumer, the scientific interest in the mechanisms underlying their presumed effects, such as pathogen inhibition, immune modulation or anti-carcinogenicity, has grown continuously in recent years. Some of these effects have been established by several independent studies, but others are still controversial. This review relates the health claims made for the pro- and prebiotic food products to the facts established by in vivo and in vitro studies. The assessment of pro- and prebiotic effects on the microbial gut ecosystem is highly improved and facilitated by the application of molecular methods. Biotechnological aspects of the production of pro- and prebiotics are discussed.     

肺部菌群和肠道菌群在两种常见肺疾病中 作用的研究进展

哮喘、慢性阻塞性肺疾病(COPD)是常见高发的肺部疾病,相关发病机制尚待阐明。近年来,菌群对哮喘、COPD的发生发展的作用越来越引起重视。本文梳理了近期肺部菌群和肠道菌群在哮喘、COPD中的作用及机制相关文献,分别从肺部菌群和肠道菌群的角度,分析它们对哮喘、COPD的作用机制以及肺部菌群和肠道菌群之间相互调控的联系,以期进一步深入了解菌群在常见肺部疾病中的意义,为寻找更有效的防治哮喘、COPD的作用靶点或者分子提供相关可借鉴的思路。     

Effects of inulin and lactulose on the intestinal morphology of calves

For some time now prebiotics have been proposed to improve health by stimulation of beneficial bacteria in the intestine of humans and animals. The current study is aiming to show effects of feeding of either 2% inulin or 2% lactulose in milk replacer on performance and intestinal morphology of male Holstein-Friesian calves. After 20 weeks of feeding inulin led to significantly higher daily weight gains than lactulose while control animals ranged between the experimental feedings. Ingestion of milk replacer was reduced in lactulose treated animals. Additionally differences of villus height in jejunum (P = 0.07) and ileum (P = 0.03) could be found with an increase for lactulose treated animals and a decrease for inulin treated animals. In ileum the density of proliferative epithelial cells tended to be lower in inulin treated and higher in lactulose treated animals (P = 0.08). Both inulin and lactulose tended to decrease the quantity of goblet cells in the tips of ileal villi (P = 0.07). Both prebiotics can affect performance and intestinal morphology of calves and may as such affect animal health. But effects differ between substances.     

益生菌在炎症性肠病治疗中的研究进展

益生菌（Probiotics）是一类能够促进肠道微生物菌群平衡,对宿主健康或生理功能产生有益作用的活性微生物。目前广泛应用于生命健康领域、科学研究、生物工程、工农业以及食品安全。大量国内外研究表明益生菌在降血压、降血糖、降血脂、抗过敏、抗炎、调节免疫、维持肠道菌群平衡等方面具有积极作用。炎症性肠病的病因和发病机制尚未完全明确,现多认为与遗传、环境、感染、免疫以及肠道微生物多因素相互作用有关。益生菌通过多种机制介导,在临床治疗炎症性肠病中扮演着重要角色。     

基于肠道微生态改善的益生菌抗糖尿病作用机制研究进展

2型糖尿病(type 2 diabetes, T2D)会引起糖脂代谢紊乱,严重危害人类健康,为了防治这一流行病,急需寻找安全和无副作用的抗糖尿病的方法,其中,基于微生物方法治疗T2D最常见的策略是补充益生菌,其可通过对不同组织和代谢通路的调节来实现抗糖尿病的功效。益生菌摄入可通过降低慢性低度炎症,减少氧化应激,调节肠道菌群,增加短链脂肪酸含量来达到调控血糖的目的;通过增加胆固醇与胆盐的共沉淀作用,胆固醇在胃肠道内转化为粪甾醇,降低肝脏中3-羟基-3-甲基戊二酸单酰辅酶A还原酶活性,降低胆固醇转运体的表达及对脂肪细胞的调节来达到降脂的目的。本综述系统总结了益生菌抗糖尿病现状和基于肠道微生态的抗糖尿病分子机制,以期为益生菌作为降糖降脂等保健产品的开发利用提供理论依据。     

The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice

The presence of a complex and diverse intestinal flora is functionally important for regulating intestinal mucosal immune responses. However, the extent to which a balanced intestinal flora regulates systemic immune responses is still being defined. In order to specifically examine whether the acquisition of a less complex flora influences responses to immunization in the pre-weaning stages of life, we utilize a model in which infant mice acquire an intestinal flora from their mothers that has been altered by broad-spectrum antibiotics. In this model, pregnant dams are treated with a cocktail of antibiotics that alters both the density and microbial diversity of the intestinal flora. After challenge with a subcutaneous immunization, the antibiotic altered flora infant mice have lower antigen specific antibody titers compared to control age-matched mice. In a second model, we examined germ free (GF) mice to analyze how the complete lack of flora influences the ability to mount normal antibody responses following subcutaneous immunization. GF mice do not respond well to immunization and introduction of a normal flora into GF mice restores the capacity of these mice to respond. These results indicate that a gastrointestinal flora reduced in density and complexity at critical time points during development adversely impacts immune responses to systemic antigens.