Long-term reduction in food allergy susceptibility in mice by combining breastfeeding-induced tolerance and TGF-ß-enriched formula after weaning.

BACKGROUND: Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence. OBJECTIVES: We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-ß supplementation after weaning would prolong it. METHODS: We quantified ovalbumin (OVA) and OVA-specific immunoglobulin levels by ELISA in milk from the EDEN birth cohort. As OVA-specific Ig was found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhoea in their 6- and 13-week-old progeny. In some experiments, a TGF-ß-enriched formula was given after weaning. RESULTS: At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhoea after six and seven OVA challenges vs. 44% and 72% in mice breastfed by naïve mothers (P = 0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA-specific IgE (P < 0.0001). At 13 weeks, although OVA-specific IgE remained low (P = 0.001), diarrhoea occurrence increased to 32% and 46% after six and seven OVA challenges in mice breastfed by OVA-exposed mothers. MMCP1 levels were not significantly inhibited. Supplementation with TGF-ß after weaning induced a strong protection in 13-week-old mice breastfed by OVA-exposed mothers compared with mice breastfed by naive mothers (0%, 13% and 32% of diarrhoea at the fifth, sixth and seventh challenges vs. 17, 42 and 78%; P = 0.05, 0.0043 and 0.0017). MMCP1 levels decreased by half compared with control mice (P = 0.02). Prolonged protection was only observed in mice rendered tolerant by breastfeeding and was associated with an improved gut barrier. CONCLUSIONS: In mice, prevention of food allergy by breastfeeding-induced tolerance is of limited duration. Nutritional intervention by TGF-ß supplementation after weaning could prolong beneficial effects of breast milk on food allergy prevention.

Beneficial effect of Lactococcus lactis NCC 2287 in a murine model of eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a severe inflammatory disease of the esophagus which is characterized histologically by an eosinophilic infiltration into the esophageal tissue. The efficacy of probiotics in the context of atopic diseases has been well investigated but, to date, there has been no study which has evaluated probiotic effects on EoE inflammation. This study sought to identify a probiotic which improves esophageal inflammation in experimental EoE. METHODS: Two candidate probiotics, Lactococcus lactis NCC 2287 and Bifidobacterium lactis NCC 2818, were tested in a murine model of EoE elicited by epicutaneous sensitization with Aspergillus fumigatus protein extract. Administration of bacterial strains in drinking water was used, respectively, as a preventive or treatment measure, or continuously throughout the study. Inflammatory parameters were assessed in the esophagus, skin, and lungs after allergen challenge. RESULTS: In this EoE model, supplementation with L. lactis NCC 2287 significantly decreased esophageal and bronchoalveolar eosinophilia but only when given as a therapeutic treatment. No significant effect on eosinophilia was observed when NCC 2287 was given as a preventive or a continuous intervention. NCC 2287 supplementation had no significant effect on immunoglobulin levels, skin symptom scores, or on transepidermal water loss. Supplementation with another probiotic, B. lactis NCC 2818, had no significant effect on esophageal eosinophilia. CONCLUSION: We identified a L. lactis strain, able to attenuate esophageal eosinophilic inflammation in a preclinical model of EoE. This effect is strain specific and depends on the timing and duration of bacterial supplementation. Confirmation of these observations in human clinical trials is warranted.

Genetic and molecular mechanisms leading to eosinophilic esophagitis.

From the epidemiologic studies, to the first genome wide association study in 2010, the understanding of the molecular pathogenesis of EoE has been both inspiring and puzzling. Epidemiologic studies have highlighted the contribution of the genetic in the EoE disease by emphasizing the presence of familial type of EoE, but has also revealed the complexity of its transmission that does not follow a Mendelian inheritance. The molecular pathogenesis advances have helped in the understanding of the mechanisms underlying this esophageal inflammation but has also allow the identification of candidate genes for which single nucleotide polymorphisms (SNP) are associated with the disease. Recently, the genome wide analysis of more than half a million single nucleotide polymorphism has allowed the identification of gene variations associated with the EoE disease and has led to substantial advance in the understanding of the molecular mechanisms leading to EoE. Undeniably, EoE is a complex polygenic disease and we certainly are only at the ground level of its detailed comprehension.

Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: Probiotics are defined as 'living micro-organisms that when administered in adequate amounts confer a health benefit to the host'. Different probiotic strains have been investigated for beneficial effects on allergic disorders. The purpose of the current study was to evaluate the effect of orally administering the probiotic Nestlé culture collection (NCC)2818 Bifidobacterium lactis strain on immune parameters and nasal symptom scores in subjects suffering from seasonal allergic rhinitis (SAR). SUBJECTS/METHODS: The study was a double-blinded, parallel, randomized placebo-controlled trial conducted during the peak of the pollen season. Adult subjects with clinical history of SAR and positive skin prick test to grass pollen were recruited. The subjects received B. lactis NCC2818 or placebo for 8 weeks and completed symptom questionnaires every week. Whole blood was collected at baseline (V1), 4 weeks (V2) and 8 weeks (V3) to measure immune parameters. RESULTS: Concentrations of Th-2 cytokines, secreted by stimulated blood lymphocytes, were significantly lower in the probiotic group compared with the placebo group at V3 (interleukin (IL)-5, P=0.016; IL-13, P=0.005). Total nasal symptom scores were significantly lower in the second month of the study (weeks 5-8) in the probiotic group compared with the placebo group (P=0.03). Also, percentages of activated CD63 expressing basophils were significantly lower in the probiotic group at V2 (P=0.02). CONCLUSIONS: Oral administration of the probiotic NCC2818 mitigates immune parameters and allergic symptoms during seasonal exposure. These promising results warrant that B. lactis NCC2818 be investigated further in large-scale trials for management of respiratory allergy.

A new dextran-graft-polybutylmethacrylate copolymer coated on 316L metallic stents enhances endothelial cell coverage.

Amphiphilic copolymers based on the copolymerization of hydrophilic and hydrophobic moieties offer versatility in various biomedical material applications. Here, a new biocompatible copolymer of dextran-graft-polybutylmethacrylate is synthesized for the coating of metallic endovascular stents. Coating of metallic surfaces is performed and analyzed by X-ray photoelectron spectroscopy, attenuated total reflection Fourier transform infrared spectroscopy, contact angle measurement, atomic force microscopy and scanning electron microscopy before and after deformation corresponding to stent deployment by a balloon catheter. In the conditions described here, the resulting coating is smooth and uniform with neither cracks nor detachment after stent expansion. Interestingly, surfaces coated with the copolymer greatly improve in vitro adhesion and growth of endothelial cells. This copolymer provides new opportunities for implanted biomaterials.

Dietary polyphenols in the prevention and treatment of allergic diseases.

Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations.

Polyphenol-enriched apple extract attenuates food allergy in mice.

BACKGROUND: The immune system may be modulated with nutrition to prevent the development or to treat the symptoms of allergy. Among other foods, consumption of apples has been linked to reduced incidence of atopic dermatitis and respiratory allergy. OBJECTIVE: We evaluated the efficacy and mechanisms of a polyphenol-enriched apple extract in reducing symptoms of food allergy. METHODS: In a model of food allergy to ovalbumin (OVA), BALB/c mice were fed with an apple extract either during sensitization or just before the challenge. After the challenge, allergic symptoms were scored, OVA-specific serum immunoglobulins were determined by ELISA, cytokine production by mesenteric lymph node (MLN) cells was measured by a multiplex assay and gene expression profiles in the intestine were addressed using quantitative real-time PCR. RESULTS: Consumption of the apple extract reduced symptoms of food allergy upon challenge. This was paralleled by reduced levels of intestinal mast cell protease, diminished cytokine secretion by MLN cells and reduced local intestinal mRNA expression of various T-helper type-2 associated and pro-inflammatory genes. Mechanistic studies suggested decrease of mediator release by effector cells and reduction of allergenicity by protein-polyphenol interaction as potential mechanisms responsible for protection. CONCLUSION: Polyphenol-enriched apple extract can attenuate food allergy symptoms in sensitized mice via two distinct possible mechanisms.

Comparative studies on the secretion and activation of MMPs in two reconstructed human skin models using HaCaT- and HaCaT-ras-transfected cell lines.

Matrix metalloproteinases play an important role in tissue regeneration, wound healing and tumor invasion. Our previous studies have shown a higher motility of HaCaT-ras-transfected cells compared with HaCaT or normal human keratinocytes (NHK) in correlation with a higher secretion of MMP-2 (72 kDa) or MMP-9 (92 kDa), according to the medium used for cell cultures. Presently, the expression and activity of MMPs were investigated in two reconstructed skin models, using a dead de-epidermized dermis (DED) or a dermal substitute including living fibroblasts. In all experiments, MMP-9 was essentially secreted by NHK and to a greater extent by HaCaT cells. Its active form (86 kDa) was only detected in both reconstructed skin models according to keratinocyte differentiation. MMP-2 was mainly secreted by living fibroblasts included in the dermal substitute skin model. In this case, its activation was up-regulated when HaCaT cell lines were seeded onto the dermal substitute according to their culture at air/liquid interface as shown for MMP-9. The collagenase MMP-1 and stromelysin-1 (MMP-3), susceptible to activate pro-MMP-2 and -9, respectively, were detected in their inactive form by ELISA. MMP-1 was expressed in both models but MMP-3 required the presence of living fibroblasts. Their activities were not detected using specific fluorogenic substrates. In the skin equivalent model using HaCaT, the extensive secretion and activation of MMP-2 and MMP-9 could explain the defect observed in basal membrane reconstruction, suggesting a direct interaction of HaCaT with fibroblasts.