Non-Digestible Oligosaccharides and Short Chain Fatty Acids as Therapeutic Targets against Enterotoxin-Producing Bacteria and Their Toxins.

Enterotoxin-producing bacteria (EPB) have developed multiple mechanisms to disrupt gut homeostasis, and provoke various pathologies. A major part of bacterial cytotoxicity is attributed to the secretion of virulence factors, including enterotoxins. Depending on their structure and mode of action, enterotoxins intrude the intestinal epithelium causing long-term consequences such as hemorrhagic colitis. Multiple non-digestible oligosaccharides (NDOs), and short chain fatty acids (SCFA), as their metabolites produced by the gut microbiota, interact with enteropathogens and their toxins, which may result in the inhibition of the bacterial pathogenicity. NDOs characterized by diverse structural characteristics, block the pathogenicity of EPB either directly, by inhibiting bacterial adherence and growth, or biofilm formation or indirectly, by promoting gut microbiota. Apart from these abilities, NDOs and SCFA can interact with enterotoxins and reduce their cytotoxicity. These anti-virulent effects mostly rely on their ability to mimic the structure of toxin receptors and thus inhibiting toxin adherence to host cells. This review focuses on the strategies of EPB and related enterotoxins to impair host cell immunity, discusses the anti-pathogenic properties of NDOs and SCFA on EPB functions and provides insight into the potential use of NDOs and SCFA as effective agents to fight against enterotoxins.

Mineralization in newborn calves contributes to health, improve the antioxidant system and reduces bacterial infections.

The first phase of life of dairy calves has elevated mortality indices linked with low immunity and sanitary challenges, mainly bacterial infections are involved in the pathogenesis of diarrhea, the leading cause of death. Also, other important problem is the nutritional deficiencies, such as the mineral deficiency. Thus, the aim of this study was to evaluate whether an intramuscular mineral supplementation based on selenium, copper, potassium, magnesium and phosphorus possess beneficial effects on health of dairy calves. For this, ten calves were divided in two groups: the group A was supplemented with injectable mineral, while the group B was used as control group (without mineral supplementation). The mineral complex was administrated via intramuscularly at dose of 3 mL/animal on days 2 and 14 post-birth. The total blood was collected on days 2, 10, 20 and 30 of life of animals in order to analyze the antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)), blood count and seric biochemistry linked with proteic, lipid and carbohydrate metabolism. Feces samples were also collected on days 10, 20 and 30 of life of animals to perform the total bacterial count, parasitological exam and fecal consistency score. Moreover, the weight and corporal temperature were also evaluated. The mineral supplementation presented beneficial properties to calves from birth to the 30th of life through the increase on activity of antioxidant enzymes, improvement of immunity, and avoiding problems linked with diarrhea and anemia, can be considered an interesting approach to prevent these alterations linked with high mortality in the period of life.

Questioning the role of a neutropenic diet following hematopoetic stem cell transplantation.

The use of a neutropenic diet (ND) after hematopoietic stem cell transplantation (HSCT) was instituted more than 30 years ago as a means of preventing infection from organisms colonizing the gastrointestinal tract. Evidence supporting this practice is lacking, however, and the actual efficacy of the ND remains unknown. Institutional policy at Northwestern Memorial Hospital discontinued the use of ND in 2006. We conducted a retrospective study of 726 consecutive HSCT recipients, 363 who received an ND and 363 who received a general hospital diet, to determine the incidence of microbiologically confirmed infections during and after transplantation. Our findings indicate a higher rate of infections in the HSCT recipients who received an ND.

Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii.

BACKGROUND: Saccharomyces boulardii, a well-studied probiotic, can be effective in inflammatory gastrointestinal diseases with diverse pathophysiology, such as inflammatory bowel disease (IBD), and bacterially mediated or enterotoxin-mediated diarrhoea and inflammation. AIM: To discuss the mechanisms of action involved in the intestinal anti-inflammatory action of S. boulardii. METHODS: Review of the literature related to the anti-inflammatory effects of this probiotic. RESULTS: Several mechanisms of action have been identified directed against the host and pathogenic microorganisms. S. boulardii and S. boulardii secreted-protein(s) inhibit production of proinflammatory cytokines by interfering with the global mediator of inflammation nuclear factor kappaB, and modulating the activity of the mitogen-activated protein kinases ERK1/2 and p38. S. boulardii activates expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) that protects from gut inflammation and IBD. S. boulardii also suppresses 'bacteria overgrowth' and host cell adherence, releases a protease that cleaves C. difficile toxin A and its intestinal receptor and stimulates antibody production against toxin A. Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes. CONCLUSIONS: The multiple anti-inflammatory mechanisms exerted by S. boulardii provide molecular explanations supporting its effectiveness in intestinal inflammatory states.

Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions.

A study was conducted in healthy elderly living independently in senior housing to assess the impact of a probiotic yoghurt supplement on small intestinal bacterial overgrowth. Twenty-three participants with positive and thirteen participants with negative hydrogen breath test were studied before and after a period of 4 weeks of probiotic yoghurt administration. Intestinal permeability, plasma endotoxin levels, phagocytic activity of leucocytes, cytokine production by monocytes and free radical response of neutrophils were determined. Intestinal permeability was similar for the two groups and was unaffected by probiotic treatment. Both plasma endotoxin levels and the basal phagocytic activity of leucocytes decreased after yoghurt intake in the two groups. Exposure of monocytes and neutrophils ex vivo led to an increased cytokine response and free radical response, respectively. The normalisation of the various cytokine responses was more apparent in the group with positive breath test. In addition, the plasma levels of lipoplysaccharide binding protein and soluble CD14, lipoplysaccharide pattern recognition receptors and surrogate markers of lipoplysaccharide permeability were diminished by the end of the study. In conclusion, probiotic administration in the elderly normalises the response to endotoxin, and modulates activation markers in blood phagocytes, and therefore may help reduce low-grade chronic inflammation.

Bacterial population and innate immunity-related genes in rat gastrointestinal tract are altered by vitamin A-deficient diet.

Vitamin A and its derivatives have been shown to regulate the growth and differentiation of gastrointestinal epithelial cells; in addition, vitamin A deficiency has been convincingly shown to be associated with increased susceptibility to infection. The gastrointestinal mucosal barrier, which is a component of the innate immune system, is considered the first line of defense, as it provides a barrier between the external environment and the internal milieu. A disturbance in the integrity of the intestinal epithelium is one of the main factors involved in increased incidence of infections during vitamin A deficiency. In this study, the effects of vitamin A deficiency on microbial ecology and the expression of genes related to the intestinal mucosa's innate immunity were examined in a rat model. Using the 16s rDNA method, we demonstrate that a vitamin A-deficient (VAD) diet increases the total amount of bacteria in the gastrointestinal tract and alters the intestinal microflora. Results show a decrease in the relative proportion of Lactobacillus spp. and the simultaneous appearance of Escherichia coli strains. Lack of vitamin A significantly changed mucin (MUC) dynamics, as reflected by the enlarged goblet-cell "cup" area relative to controls; decreased MUC2 mRNA expression in the jejunum, ileum and colon of VAD rats and increased MUC3 mRNA expression in the ileum and colon of these rats. In addition, vitamin A deficiency down-regulated defensin 6 mRNA expression while up-regulating toll-like receptors 2 and 5 mRNA expressions. The current study indicates that vitamin A deficiency interferes with the integrity of the gastrointestinal mucosal barrier.

Indicators of zinc status at the population level: a review of the evidence.

The role of zinc deficiency as an important cause of morbidity and impaired linear growth has prompted the need to identify indicators of population zinc status. Three indicators have been recommended - prevalence of zinc intakes below the estimated average requirement (EAR), percentage with low serum zinc concentrations, and percentage of children aged < 5 years who are stunted. This review outlines steps to estimate the prevalence of inadequate intakes, and confirm their validity based on the EARs set by International Zinc Nutrition Collaborative Group. Next, the appropriateness of serum zinc as a biochemical marker for population zinc status is confirmed by a summary of: (a) the response of serum zinc concentrations to zinc intakes; (b) usefulness of serum zinc concentrations to predict functional responses to zinc interventions; (c) relationship between initial serum zinc and change in serum zinc in response to interventions. Height- or length-for-age was chosen as the best functional outcome after considering the responses of growth, infectious diseases (diarrhoea, pneumonia), and developmental outcomes in zinc supplementation trials and correlation studies. The potential of other zinc biomarkers such as zinc concentrations in hair, cells, zinc-metalloenzymes, and zinc-binding proteins, such as metallothionein, is also discussed. Molecular techniques employing reverse transcriptase (RT)-polymerase chain reaction to measure mRNA in metallothionein and ZIP1 transporter hold promise, as do kinetic markers such as exchangeable zinc pools (EZP) and plasma zinc turnover rates. More research is needed to establish the validity, specificity, sensitivity, and feasibility of these new biomarkers, especially in community-settings.

Bioactive substances of garlic and their role in dietoprophylaxis and dietotherapy.

Garlic is characterised by medicinal properties due to the content of over 2000 biologically active substances. Numerous commercially processed garlic forms, which differ in the content of bioactive compounds, especially sulphuric, are available on the market. The knowledge of the types of bioactive substances present in garlic and its products, their changes during treatment and pro-health influence is of crucial importance to the diet supplement producers, doctors, pharmacists and consumers. Therefore, this work has aimed to characterise the most important bioactive substances of garlic, its preparations and describe in detail the role of garlic in dietoprophylaxis and dietotherapy.

Review article: bacterial translocation in the critically ill--evidence and methods of prevention.

BACKGROUND: Delayed sepsis, systemic inflammatory response syndrome (SIRS) and multiorgan failure remain major causes of morbidity and mortality on intensive care units. One factor thought to be important in the aetiology of SIRS is failure of the intestinal barrier resulting in bacterial translocation and subsequent sepsis. AIM: This review summarizes the current knowledge about bacterial translocation and methods to prevent it. METHODS: Relevant studies during 1966-2006 were identified from a literature search. Factors, which detrimentally affect intestinal barrier function, are discussed, as are methods that may attenuate bacterial translocation in the critically ill patient. RESULTS: Methodological problems in confirming bacterial translocation have restricted investigations to patients undergoing laparotomy. There are only limited data available relating to specific interventions that might preserve intestinal barrier function or limit bacterial translocation in the intensive care setting. These can be categorized broadly into pre-epithelial, epithelial and post-epithelial interventions. CONCLUSIONS: A better understanding of factors that influence translocation could result in the implementation of interventions which contribute to improved patient outcomes. Glutamine supplementation, targeted nutritional intervention, maintaining splanchnic flow, the judicious use of antibiotics and directed selective gut decontamination regimens hold some promise of limiting bacterial translocation. Further research is required.

Kefir: a symbiotic yeasts-bacteria community with alleged healthy capabilities.

Kefir is a fermented milk beverage. The milk fermentation is achieved by the of kefir grains, a cluster of microorganisms held together by a polysaccharide matrix named kefiran. Kefir grains are an example of symbiosis between yeast and bacteria. They have been used over years to produce kefir, a fermented beverage that is consumed all over the world, although its origin is Caucasian. A vast variety of different species of organisms forming the kefir grains, comprising yeast and bacteria, have been isolated and identified. Kefir is a probiotic food. Probiotics have shown to be beneficial to health, being presently of great interest to the food industry. Kefir has been accredited with antibacterial, antifungal and antitumoural activities among other beneficial attributes. This review includes a critical revision of the microbiological composition of kefir along with its beneficial properties to human health.

Kefir: a symbiotic yeasts-bacteria community with alleged healthy capabilities

El kéfir es una bebida láctea fermentada. Los gránulo de kéfir, comunidades de microorganismos que se agrupan en una matriz polisacárida denominada kefirano, son los responsables de esta fermentación. Estos gránulos son un ejemplo de simbiosis entre levaduras y bacterias y se han utilizado a través del tiempo para producir el kéfir, que es consumido por todo el mundo a pesar de su origen caucásico. En esa relación simbiótica, que son los gránulos de kéfir, se han aislado e identificado una amplia variedad de especies microbianas que comprenden levaduras y bacterias. El kéfir es un alimento prebiótico. Los prebióticos han demostrado ser beneficiosos para la salud, siendo de gran interés para la industria alimentaria en la actualidad. Según se afirma, el kéfir ha mostrado actividades antibacterianas, antifúngicas y antitumorales, entre otros atributos beneficiosos. Este trabajo incluye una revisión crítica de la composición microbiológica del kéfir junto con sus propiedades beneficiosas para la salud humana(AU)

Kefir is a fermented milk beverage. The milk fermentation is achieved by the of kefir grains, a cluster of microorganisms held together by a polysaccharide matrix named kefiran. Kefir grains are an example of symbiosis between yeast and bacteria. They have been used over years to produce kefir, a fermented beverage that is consumed all over the world, although its origin is Caucasian. A vast variety of different species of organisms forming the kefir grains, comprising yeast and bacteria, have been isolated and identified. Kefir is a probiotic food. Probiotics have shown to be beneficial to health, being presently of great interest to the food industry. Kefir has been accredited with antibacterial, antifungal and antitumoural activities among other beneficial attributes. This review includes a critical revision of the microbiological composition of kefir along with its beneficial properties to human health(AU)

The use of bacterial spore formers as probiotics.

The field of probiosis has emerged as a new science with applications in farming and aqaculture as alternatives to antibiotics as well as prophylactics in humans. Probiotics are being developed commercially for both human use, primarily as novel foods or dietary supplements, and in animal feeds for the prevention of gastrointestinal infections, with extensive use in the poultry and aquaculture industries. The impending ban of antibiotics in animal feed, the current concern over the spread of antibiotic resistance genes, the failure to identify new antibiotics and the inherent problems with developing new vaccines make a compelling case for developing alternative prophylactics. Among the large number of probiotic products in use today are bacterial spore formers, mostly of the genus Bacillus. Used primarily in their spore form, these products have been shown to prevent gastrointestinal disorders and the diversity of species used and their applications are astonishing. Understanding the nature of this probiotic effect is complicated, not only because of the complexities of understanding the microbial interactions that occur within the gastrointestinal tract (GIT), but also because Bacillus species are considered allochthonous microorganisms. This review summarizes the commercial applications of Bacillus probiotics. A case will be made that many Bacillus species should not be considered allochthonous microorganisms but, instead, ones that have a bimodal life cycle of growth and sporulation in the environment as well as within the GIT. Specific mechanisms for how Bacillus species can inhibit gastrointestinal infections will be covered, including immunomodulation and the synthesis of antimicrobials. Finally, the safety and licensing issues that affect the use of Bacillus species for commercial development will be summarized, together with evidence showing the growing need to evaluate the safety of individual Bacillus strains as well as species on a case by case by basis.

Inulin and oligofructose: impact on intestinal diseases and disorders.

A large and diverse variety of bacteria have evolved and adapted to live in the human intestinal habitat in a symbiotic arrangement that influences both physiology and pathology in the host. Symbiosis between host and flora can be optimised by prebiotics. Inulin-type fructans have been shown to improve the metabolic functions of the commensal flora. Clinical and experimental data suggest that they also improve the gut mucosal barrier. Furthermore, modulation of the trophic functions of the flora by these prebiotics could help in the prevention of inflammatory bowel diseases. The anti-inflammatory effects of inulin or oligofructose have been assessed in the rat model of distal colitis induced by dextran sodium sulphate, which histologically resembles human ulcerative colitis, and in the trinitrobenzene sulphonic acid model that resembles human Crohn's disease. Both inulin and oligofructose stimulate colonic production of SCFA and favour the growth of indigenous lactobacilli and/or bifidobacteria. These effects are associated with reduced mucosal inflammation and decreased mucosal lesion scores. Inulin has also been tested in a placebo-controlled clinical trial in patients with relapsing pouchitis. Treatment reduced endoscopic and histological parameters of inflammation of the pouch mucosa. Inulin and oligofructose may offer an opportunity to prevent chronic inflammatory intestinal disorders, and this potential should be tested in further clinical studies.

"Starve a fever and feed a cold": feeding and anorexia may be adaptive behavioral modulators of autonomic and T helper balance.

Anorexia is a common symptom accompanying infections, but the teleology of the phenomenon remains unexplained. We hypothesize that anorexia may represent a prehistoric behavioral adaptation to fight infection by maintaining T helper (Th)2 bias, which is particularly vital in fighting bacterial pathogens. Specifically, we propose that anorexia may avert the reduction of Th2/Th1 ratio by preventing feeding-induced neurohormonal and vagal output from the gut. Emerging evidence suggests that the vagal and neurohormonal output of the gut during feeding promotes Th1 function, which is desirable in fighting viral infections. Since fever may be an adaptation to fight bacteria and "colds" are generally viral in origin, the adage "starve a fever and feed a cold" may reflect a sensible behavioral strategy to tilt autonomic and Th balance in directions that are optimal for fighting the particular type of infection. The ability to modulate T helper balance through the neurohormonal and autonomic axis by adjusting food intake may be the mechanism behind other unexplained clinical observations such as the improved outcomes of ICU patients after enteric versus parenteric feedings. Compared to the prehistoric period when bacterial infection was commonplace, the anorexic response may be less adaptive today when viruses and cancers have become common triggers of anorexia. By promoting host anorexia, cachexia, and insomnia, cancers and viruses can deter behaviors such as digestion and sleep that would raise vagal and Th1 activity against tumors and viruses. Hydration and sleep, unexplained but widely accepted recommendations for flu patients, may also work by promoting vagal and Th1 functions. Modulating feeding, hydration, and sleep may prove beneficial in treating other conditions associated with abnormal autonomic and Th balance.

Gut flora in health and disease: potential role of probiotics.

In a young evolving science, there are always more questions than answers. That is also the situation in the emerging field of Probiotics, and this was made very clear at the International Probiotics Workshop in Amsterdam. In the report of this workshop, we present a selection of the most urgent questions in the field of probiotics. In addition, we propose a few strategies for the future of probiotics research. During the workshop, 120 experts--from disciplines including Human Nutrition, Gastroenterology, Nutritional Therapy, Cell Biology, Microbiology and Immunology--discussed new views on microbe-host interactions and the role of probiotics in prevention and alleviation of gastro-intestinal, atopic and auto-immune diseases. There is a general consensus among the experts that administering defined strains can help in preventing and curing gut flora related diseases: the first clinical trials show a promising role for probiotics. But the system is very complex, and most underlying mechanisms are still unclear. Rapid progress in this field will depend largely on the collaboration between fundamental researchers from different disciplines and medical specialists. Besides, more clinical studies are required to convince authorities and the public of the value of microbial therapies.

Probiotics and health: new facts and ideas.

Many trials on probiotics are now published that use established methods to demonstrate their clinical efficacy. Convincing progress has been made in the field of inflammatory bowel disease and allergy prevention in infants. Experimental studies show clear differences (and even sometimes opposite effects) between apparently closely related probiotics and suggest new mechanisms for the observed effects, such as immunostimulation by bacterial DNA and interaction with Toll-like receptors and dendritic cells in the gastrointestinal tract.

Probiotics as modulators of the gut flora.

Probiotic ingestion can be recommended as a preventative approach to maintaining the balance of the intestinal microflora and thereby enhance 'well-being'. Research into the use of probiotic intervention in specific illnesses and disorders has identified certain patient populations that may benefit from the approach. Undoubtedly, probiotics will vary in their efficacy and it may not be the case that the same results occur with all species. Those that prove most efficient will likely be strains that are robust enough to survive the harsh physico-chemical conditions present in the gastrointestinal tract. This includes gastric acid, bile secretions and competition with the resident microflora. A survey of the literature indicates positive results in over fifty human trials, with prevention/treatment of infections the most frequently reported output. In theory, increased levels of probiotics may induce a 'barrier' influence against common pathogens. Mechanisms of effect are likely to include the excretion of acids (lactate, acetate), competition for nutrients and gut receptor sites, immunomodulation and the formation of specific antimicrobial agents. As such, persons susceptible to diarrhoeal infections may benefit greatly from probiotic intake. On a more chronic basis, it has been suggested that some probiotics can help maintain remission in the inflammatory conditions, ulcerative colitis and pouchitis. They have also been suggested to repress enzymes responsible for genotoxin formation. Moreover, studies have suggested that probiotics are as effective as anti-spasmodic drugs in the alleviation of irritable bowel syndrome. The approach of modulating the gut flora for improved health has much relevance for the management of those with acute and chronic gut disorders. Other target groups could include those susceptible to nosocomial infections, as well as the elderly, who have an altered microflora, with a decreased number of beneficial microbial species. For the future, it is imperative that mechanistic interactions involved in probiotic supplementation be identified. Moreover, the survival issues associated with their establishment in the competitive gut ecosystem should be addressed. Here, the use of prebiotics in association with useful probiotics may be a worthwhile approach. A prebiotic is a dietary carbohydrate selectively metabolised by probiotics. Combinations of probiotics and prebiotics are known as synbiotics.

Probiotics and non-intestinal infectious conditions.

Orally ingested probiotic micro-organisms do not exert health effects exclusively in the intestine. Some strains can alleviate or prevent bacterial, fungal or viral infections in other organs by stimulation of the immune system. By preservation or improvement of the barrier function of the intestinal mucosa, they may inhibit translocation of potential pathogens and thus prevent infections of the blood stream and other tissues and organs. Modulation of the intestinal microflora can affect the local microflora of the urogenital tract and possibly of the oral cavity. Finally, some strains of orally ingested bacteria reach target organs like the urogenital tract in a viable state; alternatively they can be applied locally. Despite the infection-preventing properties of probiotic bacteria, lactic acid bacteria have rarely been identified in infections of the blood stream, heart valves and other organs, usually only in patients with severe disease. It is the general opinion that in most cases the source of infection was the commensal microflora of the intestine or the oral cavity. Until now only one case of infection associated with administration of a probiotic strain has been published. The most promising health-promoting effects have been seen in vaginosis, urinary tract infections, Helicobacter pylori gastritis and infections of the respiratory tract in children. More controlled clinical trials with sufficient numbers of participants are needed to determine the scientific basis for the use of probiotic bacteria in infections in locations of the body other than the intestine.