Importance of maternal diet in the training of the infant's immune system during gestation and lactation

Latest forecasts predict that half of the European population will be allergic within the coming 15 years, with food allergies contributing substantially to the total burden; preventive measures are urgently needed. Unfortunately, all attempted alimentary strategies for primary prevention of allergic diseases through allergen avoidance so far have failed. This also holds true for the prevention of food allergies in breastfed infants by the common practice of excluding certain foods with allergenic potential from the maternal diet. As a preventive measure, therefore, exclusion diets should be discouraged. They can exhaust nursing mothers and negatively impact both their nutritional status as well as their motivation to breastfeed. A prolonged exclusion diet may be indicated solely in cases of doctor-diagnosed food allergy following rigid medical tests (e.g. double-blind placebo-controlled food challenges). Indicated cases usually involve exclusion of only a few food items. Continued breastfeeding is generally important for many aspects of the infant's health, including the training of the infant's immune responses to foreign compounds and avoidance of overshooting inflammatory responses. Recent studies suggest that the presence of maternal dietary proteins in amniotic fluid, cord blood, and human milk might support the induction of tolerance towards solid foods in infants. These are exactly the same species of proteins or remnants thereof that, in comparatively few cases, trigger allergic responses. However, the insight that the proteins of maternal dietary origin in human milk are more likely to be cure (or, more precise, directing prevention) than curse has still largely evaded the attention of health care professionals consulted by worried breastfeeding mothers. In this paper, we summarize recent literature on the importance of exposure to dietary proteins in the establishment of immunological tolerance and hence prevention of allergic disease. Multiple organizations have used the scientific knowledge to build (local) guidelines (e.g. AAAAI, EAACI, BSACI) that can support health care professionals to provide the best strategy to prevent the onset of allergic diseases. We thus hope to clarify existing confusion about the allergenic propensities of dietary proteins during early life, which has contributed to exaggerated fears around the diet of pregnant and breastfeeding mothers

Mice co-administrated with partially hydrolysed whey proteins and prebiotic fibre mixtures show allergen-specific tolerance and a modulated gut microbiota

Non-breastfed infants at-risk of allergy are recommended to use a hydrolysed formula before the age of 6 months. The addition of prebiotics to this formula may reduce the allergy development in these infants, but clinical evidence is still inconclusive. This study evaluates (1) whether the exposure duration to different prebiotics alongside a partially hydrolysed whey protein (pHP) influences its' effectiveness to prevent allergy development and (2) whether the gut microbiota plays a role in this process. Mice orally sensitised with whey and/or cholera toxin were orally treated for six days before sensitization with phosphate buffered saline, whey or pHP to potentially induce tolerance. Two groups received an oligosaccharide diet only from day -7 until -2 (GFshort and GFAshort) whereas two other groups received their diets from day -15 until 37 (GFlong and GFAlong). On day 35, mice underwent an intradermal whey challenge, and the acute allergic skin response, shock score, and body temperatures were measured. At day 37, mice received whey orally and serum mouse mast cell protease-1, SLPI and whey-specific antibodies were assessed. Faecal samples were taken at day -15, -8 and 34. Feeding mice pHP alone during tolerance induction did not reduce ear swelling. The tolerance inducing mechanisms seem to vary according to the oligosaccharide-composition. GFshort, GFlong, and GFAlong reduced the allergic skin response, whereas GFAshort was not potent enough. However, in the treatment groups, the dominant Lactobacillus species decreased, being replaced by Bacteroidales family S24- 7 members. In addition, the relative abundance of Prevotella was significantly higher in the GFlong, GFAshort and GFAlong groups. Co-administration of oligosaccharides and pHP can induce immunological tolerance in mice, although tolerance induction was strongest in the animals that were fed oligosaccharides during the entire protocol. Some microbial changes coincided with tolerance induction, however, a specific mechanism could not be determined based on these data

The mycotoxin deoxynivalenol facilitates allergic sensitization to whey in mice

Intestinal epithelial stress or damage may contribute to allergic sensitization against certain food antigens. Hence, the present study investigated whether impairment of intestinal barrier integrity by the mycotoxin deoxynivalenol (DON) contributes to the development of whey-induced food allergy in a murine model. C3H/HeOuJ mice, orally exposed to DON plus whey once a week for 5 consecutive weeks, showed whey-specific IgG1 and IgE in serum and an acute allergic skin response upon intradermal whey challenge, although early initiating mechanisms of sensitization in the intestine appeared to be different compared with the widely used mucosal adjuvant cholera toxin (CT). Notably, DON exposure modulated tight-junction mRNA and protein levels, and caused an early increase in IL-33, whereas CT exposure affected intestinal γδ T cells. On the other hand, both DON- and CT-sensitized mice induced a time-dependent increase in the soluble IL-33 receptor ST2 (IL-1R1) in serum, and enhanced local innate lymphoid cells type 2 cell numbers. Together, these results demonstrate that DON facilitates allergic sensitization to food proteins and that development of sensitization can be induced by different molecular mechanisms and local immune responses. Our data illustrate the possible contribution of food contaminants in allergic sensitization in humans.Mucosal Immunology advance online publication, 17 February 2016; doi:10.1038/mi.2016.13

Значение мотивации персонала на предприятии

Основная цель – систематизировать сведения о мотивации персонала и его значении на предприятии

Mouse genetic model for antigen-induced airway manifestations of asthma

Allergic asthma is a genetically complex disease characterized by allergen-specific immunoglobulin (Ig)E, eosinophilic inflammation of the lungs and airway hyper-responsiveness to bronchospasmogenic stimuli. In this study, we compared 13 recombinant congenic ( RC) mouse strains in an ovalbumin model of allergic asthma. Different intensities and types of responses are observed throughout the RC strains. Intensities range from resistance to asthma in CcS05, to a very severe bronchoconstrictive reaction upon methacholine challenge for the parental STS strain. All strains show a 'modified' Th2 response except CcS14, which shows a 'true' Th2 response. When data from all strains are pooled, airway reactivity shows significant correlations with the serum Ig levels and the levels of interleukin (IL)-4, IL-5 and IL-13 in the broncho-alveolar lavage (BAL), at low dosage of methacholine (below 25 mg/ml), whereas at high dosage airway reactivity only correlates with BAL neutrophil levels. This indicates that at least two different mechanisms are involved in the airway reactivity to methacholine. None of these correlations can be found in every individual strain, which demonstrates that the asthma traits in this mouse model are genetically dissociated and that the loci can be genetically mapped

The development of allergic inflammation in a murine house dust mite asthma model is suppressed by synbiotic mixtures of non-digestible oligosaccharides and Bifidobacterium breve M-16V

PURPOSE: The incidence and severity of allergic asthma is rising, and novel strategies to prevent or treat this disease are needed. This study investigated the effects of different mixtures of non-digestible oligosaccharides combined with Bifidobacterium breve M-16V (BB) on the development of allergic airway inflammation in an animal model for house dust mite (HDM)-induced allergic asthma. METHODS: BALB/c mice were sensitized intranasally (i.n.) with HDM and subsequently challenged (i.n.) with PBS or HDM while being fed diets containing different oligosaccharide mixtures in combination with BB or an isocaloric identical control diet. Bronchoalveolar lavage fluid (BALF) inflammatory cell influx, chemokine and cytokine concentrations in lung homogenates and supernatants of ex vivo HDM-restimulated lung cells were analyzed. RESULTS: The HDM-induced influx of eosinophils and lymphocytes was reduced by the diet containing the short-chain and long-chain fructo-oligosaccharides and BB (FFBB). In addition to the HDM-induced cell influx, concentrations of IL-33, CCL17, CCL22, IL-6, IL-13 and IL-5 were increased in supernatants of lung homogenates or BALF and IL-4, IFN-γ and IL-10 were increased in restimulated lung cell suspensions of HDM-allergic mice. The diet containing FFBB reduced IL-6, IFN-γ, IL-4 and IL-10 concentrations, whereas the combination of galacto-oligosaccharides and long-chain fructo-oligosaccharides with BB was less potent in this model. CONCLUSION: These findings show that synbiotic dietary supplementation can affect respiratory allergic inflammation induced by HDM. The combination of FFBB was most effective in the prevention of HDM-induced airway inflammation in mice

Identification of peptides with tolerogenic potential in a hydrolysed whey-based infant formula

BACKGROUND: Failure to induce oral tolerance may result in food allergy. Hydrolysed cow's milk-based infant formulas are recommended in subjects with a high risk of developing allergic disease. Presentation of T cell epitopes is a prerequisite to generate regulatory T cells that could contribute to oral tolerance. OBJECTIVE: To investigate whether a specific hydrolysed whey-based infant formula contains peptides that function as T cell epitopes to support the development of oral tolerance to whey. METHODS: First, a novel liquid chromatography-mass spectrometry (LC-MS) method was developed to characterize β-lactoglobulin-derived peptides present in a specific infant formula with a focus on region AA#13-48 of β-lactoglobulin, which has previously been described to contain T cell epitopes with tolerogenic potential. Second, the formula was subjected to the ProImmune ProPresent® antigen presentation assay and MHC class II binding algorithm to identify relevant HLA-DRB1-restricted peptides. Third, identified peptides were tested on human cow's milk protein-specific T cell lines to determine T cell recognition. RESULTS: Thirteen peptides of minimal 9AAs long that overlap with AA#13-48 of β-lactoglobulin were identified. Six of them were found across all batches analysed. It was further confirmed that these peptides were processed and presented by human dendritic cells. The identified HLA-DRB1-restricted peptides were correlated to AA#11-30 and AA#23-39 of β-lactoglobulin. Importantly, the proliferation assay showed that the synthetic peptides were recognized by cow's milk protein-specific T cell lines and induced T cell proliferation. CONCLUSION AND CLINICAL RELEVANCE: This study demonstrates that the tested hydrolysed infant formula contains functional HLA-DRB1-restricted T cell epitopes, which can potentially support the development of oral tolerance to whey