Irritable bowel syndrome (IBS) is a disorder of chronic abdominal pain, altered bowel habit and abdominal distension. It is the commonest cause of referral to gastroenterologists in the developed world and yet current therapeutic strategies are often unsatisfactory. There is now increasing evidence linking alterations in the gastrointestinal (GI) microbiota and IBS. Changes in faecal and mucosa-associated microbiota, post-infectious IBS, a link with small intestinal bacterial overgrowth and an up-regulation of the GI mucosal immune system all suggest a role for the GI microbiota in the pathogenesis of IBS. Given this evidence, therapeutic alteration of the GI microbiota by probiotic bacteria could be beneficial. The present paper establishes an aetiological framework for the use of probiotics in IBS and comprehensively reviews randomised placebo-controlled trials of probiotics in IBS using multiple electronic databases. It highlights safety concerns over the use of probiotics and attempts to establish guidelines for their use in IBS in both primary and secondary care.

The problem of obesity in Scotland has reached epidemic proportions and this reality is recognised at Scottish Government level. The financial impact of treating obesity and obesity-related disease is substantial and in Scotland the cost was estimated at £171×106 in 2001 but only a small proportion of this estimate included weight-loss interventions. The Scottish Intercollegiate Guidelines Network (SIGN) define clinical guidelines as ‘systematically developed statements to help practitioner and patient decisions’ that ‘provide recommendations for effective practice in the management of clinical conditions where variations in practice are known to occur and where effective care may be known not to occur’. The evidence base for successful interventions has progressed since the publication by SIGN of Obesity in Scotland: Integrating Prevention with Weight Management in 1996 and Management of Obesity in Children and Young People in 2003. In 2007 SIGN commissioned a review of these two publications. In 2006 the National Institute for Health and Clinical Excellence (NICE) published a comprehensive obesity guideline and to avoid duplication of effort SIGN used the ADAPTE guideline adaptation framework to utilise and update evidence tables produced by NICE (where appropriate) as a basis for considered judgement. The new SIGN guideline is due for publication in 2010 and addresses children, young people (<18 years old) and adults. It will provide evidence-based recommendations on primary prevention of obesity (defined as intervention when individuals are at a healthy weight and/or overweight to prevent or delay the onset of obesity) within the clinical setting and treatment by lifestyle measures, drugs and surgery.

Much interest has been focused on the relationship between glycaemic index and body-weight loss, some of which is fuelled by popular media. However, there is a number of potential mechanisms that could be triggered by reducing the glycaemic index of the carbohydrate consumed in the diet. For example, the effect of foods on the gastrointestinal tract and the effect on blood glucose both could lead to potential appetite effects. Acute meal studies seem to point to an effect of glycaemic index on appetite regulation. However, the results of longer-term studies of weight loss are not as clear. In the present review a possible reason for this variation in outcome from the weight-loss studies will be discussed. The present review focuses on the possibility that the fermentable fibre content of the low-glycaemic-index diet may be important in weight-loss efficacy. A novel receptor that binds SCFA, the products of carbohydrate fermentation, has recently been described on the enteroendocrine L-cell in the colon. This cell releases a number of anorectic hormones and could offer an explanation of the appetite suppressant effects of fermentable carbohydrates. It could also explain the variability in the results of glycaemic-index weight-loss studies.

Obesity is a serious problem that affects children from diverse ethnic backgrounds in both industrialised and developing countries. Worldwide, an estimated twenty-two million children <5 years of age were overweight in 2007. In the UK if current trends continue an estimated one-quarter of all children <16 years of age will be obese by 2050. Recent evidence suggests that most obesity is established during the preschool years, and because one in five obese 4 year olds will become obese adults this situation has major implications for public health. The causes of obesity in preschool children are complex and multifactorial. Although 30–50% of the predisposition towards obesity in preschool children can be explained by genetic factors, environmental influences also play a crucial role. The preschool period in particular is a pivotal time during which long-term dietary and physical activity habits are established, with potential lifelong effects on health. However, research in this age-group is limited. Previous studies have aimed to improve diet, increase physical activity and achieve behavioural change. However, few of these studies have been successful and there is an urgent need, therefore, for the development of evidence-based interventions aimed at the prevention of preschool obesity.

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.

The phenotype of an individual is the result of complex interactions between genome, epigenome and current, past and ancestral environment leading to a lifelong remodelling of the epigenomes. The genetic information expression contained in the genome is controlled by labile chromatin-associated epigenetic marks. Epigenetic misprogramming during development is widely thought to have a persistent effect on the health of the offspring and may even be transmitted to the next generation. The epigenome serves as an interface between the environment and the genome. Dietary factors, including folate involved in C1 metabolism, and other social and lifestyle exposures have a profound effect on many aspects of health including ageing and do so, at least partly, through interactions with the genome, which result in altered gene expression with consequences for cell function and health throughout the life course. Depending on the nature and intensity of the environmental insult, the critical spatiotemporal windows and developmental or lifelong processes involved, epigenetic alterations can lead to permanent changes in tissue and organ structure and function or to phenotypic changes that can (or cannot) be reversed using appropriate epigenetic tools. Moreover, the flexibility of epigenetic marks may make it possible for environmental, nutritional and hormonal factors or endocrine disruptors to alter, during a particular spatiotemporal window in a sex-specific manner, the sex-specific methylation or demethylation of specific CpG and/or histone modifications underlying sex-specific expression of a substantial proportion of genes. Moreover, genetic factors, the environment and stochastic events change the epigenetic landscape during the lifetime of an individual. Epigenetic alterations leading to gene expression dysregulation accumulate during ageing and are important in tumorigenesis and age-related diseases. Several encouraging trials suggest that prevention and therapy of age- and lifestyle-related diseases by individualised tailoring to optimal epigenetic diets or drugs are conceivable. However, these interventions will require intense efforts to unravel the complexity of these epigenetic, genetic and environment interactions and to evaluate their potential reversibility with minimal side effects.

The WHO estimate that >1×106 deaths in Europe annually can be attributed to diseases related to excess body weight, and with the rising global obesity levels this death rate is set to drastically increase. Obesity plays a central role in the metabolic syndrome, a state of insulin resistance that predisposes patients to the development of CVD and type 2 diabetes mellitus. Obesity is associated with low-grade chronic inflammation characterised by inflamed adipose tissue with increased macrophage infiltration. This inflammation is now widely believed to be the key link between obesity and development of insulin resistance. In recent years it has been established that activation of pro-inflammatory pathways can cross talk with insulin signalling pathways via a number of mechanisms including (a) down-regulation of insulin signalling pathway proteins (e.g. GLUT4 and insulin receptor substrate (IRS)-1), (b) serine phosphorylation of IRS-1 blocking its tyrosine phosphorylation in response to insulin and (c) induction of cytokine signalling molecules that sterically hinder insulin signalling by blocking coupling of the insulin receptor to IRS-1. Long-chain (LC) n-3 PUFA regulate gene expression (a) through transcription factors such as PPAR and NF-κB and (b) via eicosanoid production, reducing pro-inflammatory cytokine production from many different cells including the macrophage. LC n-3 PUFA may therefore offer a useful anti-inflammatory strategy to decrease obesity-induced insulin resistance, which will be examined in the present review.

The consumption of flavonoid-rich foods and beverages has been suggested to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance. Flavonoids mediate these effects via a number of routes, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation and a potential to promote memory, learning and cognitive function. Originally, it was thought that such actions were mediated by the antioxidant capacity of flavonoids. However, their limited absorption and their low bioavailability in the brain suggest that this explanation is unlikely. Instead, this multiplicity of effects appears to be underpinned by three separate processes: first, through their interactions with important neuronal and glial signalling cascades in the brain, most notably the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways that regulate pro-survival transcription factors and gene expression; second, through an ability to improve peripheral and cerebral blood flow and to trigger angiogenesis and neurogenesis in the hippocampus; third, by their capacity to directly react with and scavenge neurotoxic species and pro-inflammatory agents produced in the brain as a result of both normal and abnormal brain ageing. The present review explores the potential inhibitory or stimulatory actions of flavonoids within these three systems and describes how such interactions are likely to underlie neurological effects.

The interaction between nutrition and infection was the subject of important work by several groups in the 1960s. The explosion of knowledge in immunology, including innate immunity, has led to increased understanding of the impact of nutrition on host defence, but much more work needs to be done in this area. In the last decade an increasing volume of work has opened up the previously obscure world of human endogenous flora. This work suggests that the microbiome, the total genetic pool of the microbiota, contributes to the already complex interaction between nutrition and infectious disease. The established concept that nutritional status, host defence and infection all impact on each other now has to be expanded into a multiple interaction, with the microbiota interacting with all three other elements. There is good evidence that the microbiome programmes host defence and drives a metabolome that impacts on energy balance, and indeed on some micronutrients. In turn, host defence shapes the microbiome, and nutritional status, particularly micronutrient status, helps determine several elements of host defence. While interventions in this area are in their infancy, the understanding of interactions that already have an enormous impact on global health is now at a threshold. The present review explores the evidence for these interactions with a view to putting potential interventions into the context of a conceptual framework.