Human Breast Milk miRNAs: Their Diversity and Potential for Preventive Strategies in Nutritional Therapy.

The endogenous miRNAs of breast milk are the products of more than 1000 nonprotein-coding genes, giving rise to mature small regulatory molecules of 19-25 nucleotides. They are incorporated in macromolecular complexes, loaded on Argonaute proteins, sequestrated in exosomes and lipid complexes, or present in exfoliated cells of epithelial, endothelial, or immune origins. Their expression is dependent on the stage of lactation; however, their detection depends on progress in RNA sequencing and the reappraisal of the definition of small RNAs. Some miRNAs from plants are detected in breast milk, opening the possibility of the stimulation of immune cells from the allergy repertoire. Each miRNA harbors a seeding sequence, which targets mRNAs, gene promoters, or long noncoding RNAs. Their activities depend on their bioavailability. Efficient doses of miRNAs are estimated to be roughly 100 molecules in the cytoplasm of target cells from in vitro and in vivo experiments. Each miRNA is included in networks of stimulation/inhibition/sequestration, driving the expression of cellular phenotypes. Three types of stress applied during lactation to manipulate miRNA supply were explored using rodent offspring: a foster mother, a cafeteria diet, and early weaning. This review presents the main mature miRNAs described from current mothers' cohorts and their bioavailability in experimental models as well as studies assessing the potential of miR-26 or miR-320 miRNA families to alter offspring phenotypes.

Early weaning leads to disruption of homeostatic and hedonic eating behaviors and modulates serotonin (5HT) and dopamine (DA) systems in male adult rats.

Early weaning is associated with disruption of eating behavior. However, little is known about the mechanisms behind it. 5HT and DA systems are key regulators of homeostatic and hedonic eating behaviors, respectively. Thus, this study aims to evaluate the effects of early weaning on feeding behavior and 5HT and DA systems. For this, rats were submitted to regular (PND30) or early weaning (PND15) and between PND250 and PND300 were evaluated food intake of standard diet in response to 4 h food deprivation, during the 24 h period and per phase of the circadian cycle, in addition to the palatable food intake. Additionally, body mass and mRNA expression of 5HT1B, 5HT2C, SERT, DRD1 and DRD2 were evaluated in the hypothalamus and brainstem. The results demonstrate that early weaning promoted an increase in standard food intake in response to a 4 h food deprivation in the 24 h period and in the dark phase of the circadian cycle, in addition to an increased palatable food intake. No differences in body mass between regular or early weaning were observed. In the hypothalamus, increased mRNA expression of SERT and DRD1 was observed, but decreased 5HT1B mRNA expression. In the brainstem, the expression of 5HT1B, SERT, 5HT2C, DRD1 and DRD2 was increased in early weaned rats. In a nutshell, the stress promoted by early weaning has programmed the animals to be hyperphagic and to increase their palatable food intake, which was associated with modulation of 5HT and DA systems.

Effectiveness of an antenatal maternal supplementation with prebiotics for preventing atopic dermatitis in high-risk children (the PREGRALL study): protocol for a randomised controlled trial.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory disease affecting 10%-15% of children in Europe. There is a need for new primary preventive therapeutic strategies in at-risk populations. Recent research has indicated that atopic diseases are associated with a disrupted gut microbial 'balance' in early life raising the possibility that interventions which yield optimal patterns of microflora could improve host's health. Prebiotics, sugars with immunomodulatory properties that stimulate the diversity of the digestive microbiota, are ideal candidates for such research. So far, most clinical trials have focused on improving infant gut colonisation postnatally. However, prenatal life is a crucial period during which different tolerance mechanisms are put in place. We aim to determine whether antenatal prebiotics supplementation prevents AD in high-risk children. METHODS AND ANALYSIS: This is a randomised, multicentre, double-blind, trial to evaluate the effectiveness of antenatal prebiotic maternal supplementation (galacto-oligosaccharide/inulin) in pregnant women versus placebo on the occurrence of AD at 1 year of age in at-risk children (defined as having a maternal history of atopic disease). Participating women will be randomised to daily ingestion of a prebiotics or placebo (maltodextrin) from 20 weeks' gestation until delivery. The primary outcome is the prevalence of AD at 1 year of age, using the version of the UK Working Party Diagnostic Criteria optimised for preventive studies. Key secondary endpoints are AD severity, quality of life and prebiotics tolerance. The target sample size is 376 women (188 patients per group) which will provide 80% power to detect a 33% reduction of the risk of AD in the verum group (α=0.05). The primary analysis will be based on the intention-to-treat principle. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and at international conferences. Ethics approval for the study was obtained from the institutional ethical review board of 'Comité de Protection des Personnes Sud Ouest-Outre-Mer III' of the University Hospital Centre of Bordeaux (2017/13). TRIAL REGISTRATION NUMBER: NCT03183440; Pre-results.

[The new paradigm of the developmental origin of health and diseases (DOHaD)--Epigenetics and environment: evidence and missing links]. / Le nouveau paradigme de l'origine développementale de la santé et des maladies (DOHaD)--Épigénétique, environnement: preuves et chaînons manquants.

According to the new paradigm of the Developpemental Origins of Health and Disease (DOHaD), the environmental factors to which an individual is exposed throughout his life can leave an epigenetic footprint on the genome. A crucial period is the early development, where the epigenome is particularly sensitive to the effects of the environment, and during which the individual builds up his health capital that will enable him to respond more or less well to the vagaries of life. The research challenge is to decipher the modes of action and the epigenetic mechanisms put into play by environmental factors that lead to increased disease susceptibility or resilience. The challenge for health is to translate these scientific discoveries into action through, among others, the establishment of preventive recommendations to slow down the growing incidence of non communicable diseases.