Diet and exercise are primary strategies recommended for the control of the obesity epidemic. Considerable attention is being paid to the effect of both on the immune system. However, little research has been done on the effect of diet, nutrients or exercise on the mucosal immune system. The gastrointestinal tract (gut) is not only responsible for the entry of nutrients into the organism, but also for triggering the primary immune response to orally ingested antigens. The gut-associated lymphoid tissue contains a large amount of immune cells, disseminated all along the intestine in Peyer's patches and lamina propria. Specific nutrients or their combinations, as well as the microflora, are capable of modulating the immune system through cell activation, production of signalling molecules or gene expression. We have observed an increase in T-cells as well as a decrease in B-cells from Peyer's patches, induced by diets high in fats or carbohydrates in Balb/c mice. It has also been demonstrated that exercise modulates the immune system, where moderate levels may improve its function by increasing the proliferation of lymphocytes from various sites, including gut-associated lymphoid tissue, whereas exhaustive acute exercise may cause immunosuppression. High-fat diets combined with exercise are able to induce an increase in CD3+ lymphocytes due to increased CD8+ cells and a decrease in B-cells. Explanations and consequences of the effects of diet and exercise on the gut mucosal immunity are still being explored.

Several immune functions are markers of health, biological age and predictors of longevity. A chronic oxidative and inflammatory state is the main cause of ageing and the immune system is involved in the rate of ageing. Thus, several murine models of premature ageing have been proposed owing to their early immunosenescence and oxidative stress, such as ovariectomised rats and mice, obese rats and anxious mice. In the last model, the most extensively studied by us, mice showing anxiety have an aged immune function and redox status as well as a shorter longevity in comparison with animals without anxiety of the same chronological age, being denominated prematurely ageing mice. A confirmation of the above is that the administration of diets supplemented with antioxidants improves the redox status and immune functions and increases the longevity of prematurely ageing mice. Antioxidant precursors of glutathione such as thioproline or N-acetylcysteine, which have a relevant role in ageing, have been the most widely investigated in adult prematurely ageing mice in our laboratory. In the present work, we have studied the effects of the ingestion for 5 weeks of a diet supplemented with 0·1% (w/w) thioproline+N-acetylcysteine on several functions of leucocytes from chronological old (69–73 weeks of age) prematurely ageing mice of two strains (Swiss and BALB/c). The results show an improvement of the immune functions, with their values becoming closer to those in adult animals (24±2 weeks). Thus, an adequate nutrition with antioxidants, even in aged subjects, could be a good strategy to retard ageing.

Obesity is a major public health issue as it is causally related to several chronic disorders, including type-2 diabetes, CVD and cancer. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, transplantation of the microbiota of either obese or lean mice influences body weight in the germ-free recipient mice, suggesting that the gut ecosystem is a relevant target for weight management. Indigenous gut microbes may regulate body weight by influencing the host's metabolic, neuroendocrine and immune functions. The intestinal microbiota, as a whole, provides additional metabolic functions and regulates the host's gene expression, improving the ability to extract and store energy from the diet and contributing to body-weight gain. Imbalances in the gut microbiota and increases in plasma lipopolysaccharide may also act as inflammatory factors related to the development of atherosclerosis, insulin resistance and body-weight gain. In contrast, specific probiotics, prebiotics and related metabolites might exert beneficial effects on lipid and glucose metabolism, the production of satiety peptides and the inflammatory tone related to obesity and associated metabolic disorders. This knowledge is contributing to our understanding of how environmental factors influence obesity and associated diseases, providing new opportunities to design improved dietary intervention strategies to manage these disorders.

Probiotics are bacteria, but sometimes fungi, which when taken by the oral route may give some health benefits. The most compelling evidence for beneficial effects of probiotics is in the prevention and reduction in the duration of symptoms related to gut infectious disease. There is also evidence to show that some specific probiotics are beneficial in Clostridium difficile diarrhoea in the elderly. As further and better controlled clinical studies have appeared, some specific probiotics also appear to have beneficial effects in perhaps preventing and reducing the duration of symptoms due to acquired upper respiratory tract infections. In an attempt to explain these effects, attention has turned to the effects of some specific probiotics on the immune system. There is evidence that some specific probiotics can alter monocyte and natural killer cell function in the blood. Evidence is also accumulating that taking some specific probiotics can boost antibody responses to oral and systemically administered vaccines. The effect when shown is modest and is not always seen in different studies to all vaccines, but there is enough of a trend to make the area worthy of further investigation, particularly to tease out the mechanisms involved.