The present review focuses on the specific effects of nutrients on the development of the immune system in early life. There is a big gap regarding the specific mechanisms that regulate immunity at the intestinal level and their impact in the systemic immune function. For this reason, during the last few years there has been great interest in ascertaining the mechanisms that regulate the intestinal immune function, as well as to understand how specific nutrients interact with the gut-associated lymphoid tissue. We have reviewed this topic with special emphasis on how human milk, and its components, influence the early development of intestinal immunity in breast-fed infants compared with formula-fed infants. Interactions between nutrients and intestinal microbiota have also been reviewed. Some micronutrients such as nucleotides and gangliosides, which are present in human milk and also in most foods, are able to influence immune functionality at very low concentrations. The specific action of these micronutrients on some parameters of immunity, as well as their potential mechanisms of action, have been considered in detail. However, there are limited data on how other specific nutrients, namely protein and non-protein N-containing compounds, lipids, carbohydrates, and others, such as minerals, vitamins, fibre, non-nutritional dietary compounds (flavonoids, carotenoids, phyto-oestrogens, etc), influence immunity. In the present review we have provided data regarding the potential effects of these compounds on the immune response in early life. The increasing use of functional foods by the public to improve their general health and prevent the incidence of chronic diseases has become a major area of interest within the nutrition community. Of the many functional foods available, probiotics have been most studied in infancy and childhood, particularly with regard to the prevention of allergic diseases. Infant formulae and fermented milks containing large quantities of probiotics are produced and consumed by Europeans and in other industrialized countries. In the present review we cover the clinical effects of probiotics in preventing disease during early life, as well as the potential mechanisms of interaction between probiotics and the gastrointestinal tract.

Human milk is recommended as the only alimentary source for the first six months of life. Additionally there is a medical and social need for safe and effective alternative forms of nutrition for infants who cannot be fed with breast milk. Recently the safety and efficacy of some ingredients in infant formulae, such as nucleotides have been discussed. This systematic review analyzed the available evidence to establish the efficacy, safety and dose-response effect of ribonucleotide-supplemented infant formulae (RSIFs). Randomised controlled clinical trials (RCTs) comparing RSIFs to formulae without nucleotides or breast milk were considered in this review. Outcome measures were: antibody titres to common paediatric vaccinations, total lymphocytes, lymphocyte subclasses and NK-cells, episodes of diarrhoea and acute respiratory infection. Publication quality was determined using Jadad and CONSORT guidelines. Results were combined using a random effects model and reported through standardised mean differences (WMD) or risk ratio (RR). Systematic review and meta-analysis showed that RSIFs were associated with a better antibody response to immunisation with Haemopillus influenzae vaccine [SMD 1·74 (99 %CI 1·43–2·05), P = 0·001], diphtheria toxoid [SMD 0·94 (0·75–1·12), P = 0·001], oral polio vaccine [SMD 0·73 (0·51–0·95), P = 0·001], and fewer episodes of diarrhoea [RR 0·67 (0·58–0·76), P = 0·02]. We did not find a major risk of upper respiratory infections [RR 1·11 (0·90–1·36), P = 0·50]. Available evidence suggests a positive benefit of RSFIs on infant health without any risk. These benefits begin with nucleotide addition of 1·9 mg/418·4 kJ and are maintained or increased with 10·78 mg/418·4 kJ.

The composition of fourteen infant formulae and six follow-up milks with regard to their free amino acids (including taurine), free nucleotides, orotic acid, and free and total L-carnitine content was studied. The levels found were compared with the limits established in European legislation and with the composition of human and cows' milk samples. HPLC methodologies, optimized and validated for the matrices under study, were used, except for free and total L-carnitine contents that were quantified using a flow-injection manifold, also optimized and validated for the matrices under study. Global statistical treatment of the results by cluster analysis indicated similarities between the contents of the N compounds under study of infant formulae, follow-up milks and cows' milk and differences with regard to human milk composition. The principal component analysis showed that 60·2% of the variation in data was due to the first principal component, and the second component represented 23·8% of the total information. Nucleotide profiles, orotic acid, and free and total L-carnitine contents explain the main differences observed between human milk and the other milks studied (cows' milk, infant formulae and follow-up milks). Cows' milk is distinguished from infant formulae and follow-up milks mainly owing to the different uric acid contents and free amino acids profiles.