Probiotics: their potential to impact human health

Probiotics—live microorganisms that when administered in adequate amounts confer a health benefit on the host—have been studied for both human and animal applications, and worldwide research on this topic has accelerated in recent years. This paper reviews the literature on probiotics, describes how probiotics work in human ecosystems, and outlines the impact of probiotics on human health and disease. The paper also addresses safety issues of probiotic use, suggests future developments in the field of probiotics, and provides research and policy recommendations. Product considerations and potential future developments regarding probiotics also are discussed. The authors conclude that controlled human studies have revealed a diverse range of health benefits from consumption of probiotics, due largely to their impact on immune function or on microbes colonizing the body. Additional, well-designed and properly controlled human and mechanistic studies with probiotics will advance the essential understanding of active principles, mechanisms of action, and degree of effects that can be realized by specific consumer groups. Recommendations include establishment of a standard of identity for the term “probiotic,” adoption of third-party verification of label claims, use of probiotics selectively in clinical conditions, and use of science-based assessment of the benefits and risks of genetically engineered probiotic microbes.

Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs

Data on the potential health benefits of dietary flavanols and procyanidins, especially in the context of cardiovascular health, are considerable and continue to accumulate. Significant progress has been made in flavanol analytics and the creation of phytonutrient-content food databases, and novel data emanated from epidemiological investigations as well as dietary intervention studies. However, a comprehensive understanding of the pharmacological properties of flavanols and procyanidins, including their precise mechanisms of action in vivo, and a conclusive, consensus-based accreditation of a causal relationship between intake and health benefits in the context of primary and secondary cardiovascular disease prevention is still outstanding. Thus, the objective of this review is to identify and discuss key questions and gaps that will need to be addressed in order to conclusively demonstrate whether or not dietary flavanols and procyanidins have a role in preventing, delaying the onset of, or treating cardiovascular diseases, and thus improving human life expectancy and quality of life.

The design of probiotic studies to substantiate health claims

The EC Regulation No. 1924/2006 on Nutrition and Health claims made on foods has generated considerable debate and concern among scientists and industry. At the time of writing, the European Food Safety Authority (EFSA) has not approved any probiotic claims despite numerous human trials and meta-analyses showing evidence of beneficial effects. On 29th and 30th September 2010, ten independent, academic scientists with a documented record in probiotic research, met to discuss designs for future probiotic studies to demonstrate health benefits for gut and immune function. The expert panel recommended the following: (i) always formulate a precise and concrete hypothesis, and appropriate goals and parameters before starting a trial; (ii) ensure trials have sufficient sample size, such that they are adequately powered to reach statistically significant conclusions, either supporting or rejecting the a priori hypothesis, taking into account adjustment for multiple testing (this might necessitate more than one recruitment site); (iii) ensure trials are of appropriate duration; (iv) focus on a single, primary objective and only evaluate multiple parameters when they are hypothesis-driven. The panel agreed that there was an urgent need to better define which biomarkers are considered valuable for substantiation of a health claim. As a first step, the panel welcomed the publication on the day of the meeting of EFSA's draft guidance document on immune and gut health, although it came too late for study designs and dossiers to be adjusted accordingly. New validated biomarkers need to be identified in order to properly determine the range of physiological functions influenced by probiotics. In addition, validated biomarkers reflecting risk factors for disease, are required for article 14 claims (EC Regulation No. 1924/2006). Finally, the panel concluded that consensus among scientists is needed to decide appropriate clinical endpoints for trials.

Memory for allergies and health foods: how younger and older adults strategically remember critical health information

Objectives. While older adults often display memory deficits, with practice they can sometimes selectively remember valuable information at the expense of less value information. We examined age-related differences and similarities in memory for health-related information under conditions where some information was critical to remember. Method. In Experiment 1, participants studied three lists of allergens, ranging in severity from 0 (not a health risk) to 10 (potentially fatal), with the instruction that it was particularly important to remember items to which a fictional relative was most severely allergic. After each list, participants received feedback regarding their recall of the high-value allergens. Experiment 2 examined memory for health benefits, presenting foods that were potentially beneficial to the relative’s immune system. Results. While younger adults exhibited better overall memory for the allergens, both age groups in Experiment 1 developed improved selectivity across the lists, with no evident age differences in severe allergen recall by List 2. Selectivity also developed in Experiment 2, although age differences for items of high health benefit were present. Discussion. The results have implications for models of selective memory in older age, and for how aging influences the ability to strategically remember important information within health-related contexts.

Infant feeding choices: experience, self-identity and lifestyle

In England 78% of mothers initiate breastfeeding and in the UK less than 1% exclusively breastfeed until 6 months, despite WHO recommendations to do so. This study investigated women’s infant feeding choices using in-depth interviews with 12 mothers of infants aged 7-18 weeks. Using content analysis, four themes emerged: (1) Information, Knowledge and Decision Making, (2) Physical Capability, (3) Family and Social Influences, (4) Lifestyle, Independence and Self-Identity. Whilst women were aware of the ‘Breast is Best’ message, some expressed distrust in this information if they had not been breastfed themselves. Women felt their own infant feeding choice was influenced by the perceived norm amongst family and friends. Women described how breastfeeding hindered their ability to retain their self-identities beyond motherhood as it limited their independence. Several second-time mothers felt they lacked support from health professionals when breastfeeding their second baby, even if they had previously encountered breastfeeding difficulties. The study indicates that experience of breastfeeding, and belief in the health benefits associated with it are important factors for initiation of breastfeeding, whilst decreased independence and self-identity may influence duration of breastfeeding. Intervention and support schemes should tackle all mothers, not just first-time mothers.

Selective effects of Lactobacillus casei Shirota on T cell activation, natural killer cell activity and cytokine production

Modulation of host immunity is an important potential mechanism by which probiotics confer health benefits. This study was designed to investigate the effects of a probiotic strain, Lactobacillus casei Shirota (LcS), on immune function, using human peripheral blood mononuclear cells (PBMC) in vitro. In addition, the role of monocytes in LcS-induced immunity was also explored. LcS promoted natural killer (NK) cell activity and preferentially induced expression of CD69 and CD25 on CD8+ and CD56+ subsets in the absence of any other stimulus. LcS also induced production of IL-1β, IL-6, TNF-α, IL-12 and IL-10 in the absence of lipopolysaccharide (LPS). In the presence of LPS, LcS enhanced IL-1β production, but inhibited LPS-induced IL-10 and IL-6 production, and had no further effect on TNF-α and IL-12 production. Monocyte-depletion significantly reduced the impact of LcS on lymphocyte activation, cytokine production and NK cell activity. In conclusion, LcS preferentially activated cytotoxic lymphocytes in both the innate and specific immune system, which suggests that LcS could potentiate the destruction of infected cells in the body. LcS also induced both pro-inflammatory and anti-inflammatory cytokine production in the absence of LPS, but inhibited LPS-induced cytokine production in some cases. Monocytes play an important role in LcS-induced immunological responses.

Down-regulation of the CSLF6 gene results in decreased (1,3;1,4)-beta-D-glucan in endosperm of wheat

(1,3;1,4)-beta-d-Glucan (beta-glucan) accounts for 20% of the total cell walls in the starchy endosperm of wheat (Triticum aestivum) and is an important source of dietary fiber for human nutrition with potential health benefits. Bioinformatic and array analyses of gene expression profiles in developing caryopses identified the CELLULOSE SYNTHASE-LIKE F6 (CSLF6) gene as encoding a putative beta-glucan synthase. RNA interference constructs were therefore designed to down-regulate CSLF6 gene expression and expressed in transgenic wheat under the control of a starchy endosperm-specific HMW subunit gene promoter. Analysis of wholemeal flours using an enzyme-based kit and by high-performance anion-exchange chromatography after digestion with lichenase showed decreases in total beta-glucan of between 30% and 52% and between 36% and 53%, respectively, in five transgenic lines compared to three control lines. The content of water-extractable beta-glucan was also reduced by about 50% in the transgenic lines, and the M(r) distribution of the fraction was decreased from an average of 79 to 85 x 10(4) g/mol in the controls and 36 to 57 x 10(4) g/mol in the transgenics. Immunolocalization of beta-glucan in semithin sections of mature and developing grains confirmed that the impact of the transgene was confined to the starchy endosperm with little or no effect on the aleurone or outer layers of the grain. The results confirm that the CSLF6 gene of wheat encodes a beta-glucan synthase and indicate that transgenic manipulation can be used to enhance the health benefits of wheat products.

The use of life cycle assessment to compare the environmental impact of production and feeding of conventional and genetically modified maize for broiler production in Argentina

The paper presents the methods and results of a life-cycle assessment (LCA) applied to the production of maize grain from a conventional variety compared with maize grain from a variety genetically modified to be herbicide tolerant and insect protected and to contain an enhanced oil and lysine content, and its impact when fed to broiler chickens. The findings show that there are both environmental and human health benefits of growing GM maize including lower impacts on global warming, ozone depletion, freshwater ecotoxicity and human toxicity. However, when considered in terms of the use of maize as a feed input to broiler chicken production, the benefits of the GM alternative become negligible compared to the use of conventional maize.

An illustration of the modelling of cost and efficacy data from a clinical trial

Health care providers, purchasers and policy makers need to make informed decisions regarding the provision of cost-effective care. When a new health care intervention is to be compared with the current standard, an economic evaluation alongside an evaluation of health benefits provides useful information for the decision making process. We consider the information on cost-effectiveness which arises from an individual clinical trial comparing the two interventions. Recent methods for conducting a cost-effectiveness analysis for a clinical trial have focused on the net benefit parameter. The net benefit parameter, a function of costs and health benefits, is positive if the new intervention is cost-effective compared with the standard. In this paper we describe frequentist and Bayesian approaches to cost-effectiveness analysis which have been suggested in the literature and apply them to data from a clinical trial comparing laparoscopic surgery with open mesh surgery for the repair of inguinal hernias. We extend the Bayesian model to allow the total cost to be divided into a number of different components. The advantages and disadvantages of the different approaches are discussed. In January 2001, NICE issued guidance on the type of surgery to be used for inguinal hernia repair. We discuss our example in the light of this information. Copyright © 2003 John Wiley & Sons, Ltd.

UV irradiance as a major influence on growth, development and secondary products of commercial importance in Lollo Rosso lettuce 'Revolution' grown under polyethylene films

The growth and production of anthocyanin, flavonoid and phenolic compounds were evaluated in Lollo Rosso lettuce 'Revolution' grown continuously under films varying in their ability to transmit LTV radiation (completely transparent to IN, transparent above 320, 350, 370 and 3 80 nm and completely opaque to LTV radiation). Plants were grown from seed under UV transparent and UV blocking films and destructively harvested 3-4 weeks after transplanting. Plants under a complete UV blocking film (UV400) produced up to 2.2 times more total above ground dry weight than plants under the UV transparent film. In contrast, anthocyanin content in plants under the UV blocking film was approximately eight times lower than in plants under a UV transparent film. Furthermore, there was a curvilinear relationship between the anthocyanin content and LTV wavelength cutoff such that above 370 run there was no further reduction in anthocyanin content. Fluorescence measurements indicated that photosynthetic performance index was 15% higher under the presence of UVB and UVA (UV280) than under the presence of UVA (UV320) and 53% higher than in the absence of UV radiation suggesting protection of the photosynthetic apparatus possibly by phenolic compounds. These findings are of particular importance as the potential of UV transmitting films to increase secondary compounds may offer the opportunity to produce plants commercially with increased health benefits compared to those grown under conventional films.

Mechanisms of probiosis and prebiosis: considerations for enhanced functional foods

The technologies of metagenomics and metabolomics are broadening our knowledge of the roles the human gut microbiota play in health and disease. For many years now, probiotics and prebiotics have been included in foods for their health benefits; however, we have only recently begun to understand their modes of action. This review highlights recent advances in deciphering the mechanisms of probiosis and prebiosis, and describes how this knowledge could be transferred to select for enhancing functional foods targeting different populations. A special focus will be given to the addition of prebiotics and probiotics in functional foods for infants and seniors.

Potential prebiotic activity of oligosaccharides obtained by enzymatic conversion of durum wheat insoluble dietary fibre into soluble dietary fibre

Background and aims: Epidemiological evidence indicates that cereal dietary fibre (DF) may have several cardiovascular health benefits. The underlying mechanisms have not yet been elucidated. Here, the potential nutritional effects of physico-chemical. properties modifications of durum wheat dietary fibre (DWF) induced by enzyme treatment have been investigated. Methods and results: The conversion of the highly polymerised insoluble dietary fibre into soluble feruloyl oligosaccharides of DWF was achieved by a tailored enzymatic treatment. The in vitro fermentation and release of ferulic acid by intestinal microbiota from DWF before and after the enzymatic treatment were assessed using a gut model validated to mimic the human colonic microbial environment. Results demonstrated that, compared to DWF, the enzyme-treated DWF (ETD-WF) stimulated the growth of bifidobacteria and lactobacilli. Concurrently, the release of free ferulic acid by ET-DWF was almost three times higher respect to the control. No effect on the formation of short chain fatty acids was observed. Conclusions: The conversion of insoluble dietary fibre from cereals into soluble dietary fibre generated a gut microbial fermentation that supported bifidobacteria and lactobacilli. The concurrent increase in free ferulic acid from the enzyme-treated DWF might result in a higher plasma ferulic acid concentration which could be one of the reasons for the health benefits reported for dietary fibre in cardiovascular diseases. (c) 2008 Elsevier B.V. All rights reserved.

Green tea (Camellia sinensis) catechins and vascular function

The health benefits of green tea (Camellia sinensis) catechins are becoming increasingly recognised. Amongst the proposed benefits are the maintenance of endothelial function and vascular homeostasis and an associated reduction in atherogenesis and CVD risk. The mounting evidence for the influential effect of green tea catechins on vascular function from epidemiological, human intervention and animal studies is subject to review together with exploration of the potential mechanistic pathways involved. Epigallocatechin-3-gallate, one of the most abundant and widely studied catechin found in green tea, will be prominent in the present review. Since there is a substantial inconsistency in the published data with regards to the impact of green tea catechins on vascular function, evaluation and interpretation of the inter- and intra-study variability is included. In conclusion, a positive effect of green tea catechins on vascular function is becoming apparent. Further studies in animal and cell models using physiological concentrations of catechins and their metabolites are warranted in order to gain some insight into the physiology and molecular basis of the observed beneficial effects.

Bioactive peptides from food proteins: new opportunities and challenges

Food proteins such as milk and soy are a rich source of bioactive peptides. In the last decade, research into this area has intensified and new bioactive peptide sequences have been discovered with a range of apparent biological functions; for example, antihypertensive, antioxidant, and antimicrobial effects and opiate-like qualities have been reported. These peptides could therefore lead to the development of important functional food products and ingredients for the prevention and even treatment of chronic diseases such as cardiovascular disease and cancer. Peptides can be produced by fermentation with dairy starters for instance, and by enzymatic hydrolysis with pancreatic and microbial enzymes. Further purification is typically carried out by membrane filtration and/or chromatographic methods. The production of novel bioactive peptides and their incorporation into functional food products poses several technological challenges as well as regulatory and marketing issues. Proof of efficacy is of paramount importance; this should be verified by conducting appropriate tests in vivo in animals and in humans. In addition, tests for cytotoxicity and allergenicity must be conducted. Despite all of these hurdles, scientific evidence is increasingly demonstrating the health benefits of diet-based disease prevention, and therefore new developments in this area are likely to continue both at the research and the commercialisation level.