Marie Bodinier

Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions

Probiotics and prebiotics, alone or together (synbiotics), can influence the intestinal microbiota and modulate the immune response. They may therefore be tools that can prevent or alleviate certain pathologies involving the gut immune system, such as allergies for which no treatment is yet available. This review focuses first on the definitions of probiotics, prebiotics, and synbiotics and key cells in the gut immune system. It then discusses their effects on mucosal immune stimulation. Experimental findings suggest that different probiotic species have similar effects on innate immunity by improving the mechanisms of pathogen destruction. On the contrary, their impacts seem to be variable on the adaptive immune system. Prebiotics can also exert an influence on the gut immune system via the stimulation of the autochthonous bacteria metabolism. Finally, this review focuses on the effects of food supplements on allergy. Different studies performed in humans or rodents have supported a potential role for selected probiotics and prebiotics in reducing some allergic parameters. Probiotic effects on allergy treatment are unclear, especially in human studies. However, they are potentially effective at short‐term for prevention when they are administered in perinatal conditions. A clinical study performed with an infant cohort revealed a beneficial effect of prebiotics in preventing allergic manifestations at long‐term. Further studies are nonetheless essential to confirm these findings. Food supplements offer potential tools for the prevention or treatment of allergy, but insufficient evidence is available at present to recommend their use in clinical practice.

Identification of IgE-binding epitopes on gliadins for patients with food allergy to wheat

Background:u2002 Food allergy to wheat induces different symptoms as atopic eczema/dermatitis syndrome (AEDS), urticaria and more severe reactions as wheat‐dependent exercise‐induced anaphylaxis (WDEIA). Different gliadin classes are involved in this allergy but IgE‐binding epitopes are known only on ω5‐gliadins and for WDEIA cases.

Allergy to deamidated gluten in patients tolerant to wheat: specific epitopes linked to deamidation

Gluten proteins can be modified by deamidation to enhance their solubility and technological applications. However, severe allergic reactions have been reported after the consumption of food products containing deamidated gluten (DG) in subjects tolerant to wheat. This work aimed to characterize allergen profiles for these patients in comparison with those of patients allergic to wheat and to identify IgE‐binding epitopes.

Immunoglobulin-E-binding epitopes of wheat allergens in patients with food allergy to wheat and in mice experimentally sensitized to wheat proteins.

Background At present, B cell epitopes involved in food allergy to wheat are known only for a few allergens and a few categories of patients.

Wheat gliadins modified by deamidation are more efficient than native gliadins in inducing a Th2 response in Balb/c mice experimentally sensitized to wheat allergens.

SCOPEnWheat gluten proteins such as gliadins constitute major food allergens. Gluten can be modified industrially by deamidation which increases its solubility and enhances its use as a food ingredient. Sensitization to deamidated gluten has been reported to cause severe allergic reactions with anaphylaxis. The aim of this study was therefore to compare the sensitization and elicitation potentials of native (NG) and deamidated (DG) gliadins. The reactivity pattern of mice IgE was also compared with that of DG-allergic patients.nnnMETHODS AND RESULTSnThe ability of DG to sensitize Balb/c mice using intra-peritoneal administration with aluminium hydroxide as an adjuvant, and to elicit an allergic response after a challenge, was tested in comparison with NG. Mice sensitized with DG secreted higher levels of total IgE, IL-4, gliadin-specific IgE and IgG1 than mice sensitized with NG. By contrast, mice sensitized with NG produced higher levels of gliadin-specific IgG2a and INFγ. After a challenge, histamine levels were higher in mice sensitised with DG.nnnCONCLUSIONSnDG can sensitize mice much more efficiently than NG. Moreover, this mouse model of allergy to DG revealed an IgE reactivity pattern against purified gliadins which was very similar to that of DG-allergic patients.

Sensitization and Elicitation of an Allergic Reaction to Wheat Gliadins in Mice

We developed a mouse model of allergy to wheat flour gliadins, a protein fraction containing major wheat allergens. We compared the antibody responses (i.e., specific IgE and IgG1) and the profiles of cytokines secreted by reactivated splenocytes induced after intraperitoneal injections of gliadins in three strains of mice, namely, Balb/cJ, B10.A, and C3H/HeJ. The intensities of the allergic reactions elicited by intranasal challenge were also compared. Both the sensitization and elicitation were the highest in Balb/cJ mice, whereas weak or no reaction was observed in the others strains. Interestingly, the specificity of the mouse IgE against the different gliadins (i.e., alpha-, beta-, gamma-, omega 1,2-, and omega 5-gliadin) was similar to that observed in children allergic to wheat flour. Balb/cJ mice may thus provide a relevant model for the study of sensitization and elicitation by wheat gliadins and for improving our understanding of the specific role and mechanisms of action of the different classes of gliadins.

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured.

Food allergy enhances allergic asthma in mice

BackgroundAtopic march refers to the typical transition from a food allergy in early childhood to allergic asthma in older children and adults. However the precise interplay of events involving gut, skin and pulmonary inflammation in this process is not completely understood.ObjectivesTo develop a mouse model of mixed food and respiratory allergy mimicking the atopic march and better understand the impact of food allergies on asthma.MethodsFood allergy to ovalbumin (OVA) was induced through intra-peritoneal sensitization and intra-gastric challenge, and/or a respiratory allergy to house dust mite (HDM) was obtained through percutaneous sensitization and intra-nasal challenges with dermatophagoides farinae (Der f) extract. Digestive, respiratory and systemic parameters were analyzed.ResultsOVA-mediated gut allergy was associated with an increase in jejunum permeability, and a worsening of Der f-induced asthma with stronger airway hyperresponsiveness and pulmonary cell infiltration, notably eosinophils. There was overproduction of the pro-eosinophil chemokine RANTES in broncho-alveolar lavages associated with an enhanced Th2 cytokine secretion and increased total and Der f-specific IgE when the two allergies were present. Both AHR and lung inflammation increased after a second pulmonary challenge.ConclusionGut sensitization to OVA amplifies Der f-induced asthma in mice.

Exposure to a galactooligosaccharides/inulin prebiotic mix at different developmental time points differentially modulates immune responses in mice.

Prebiotics constitute emerging tools to alleviate immune pathologies. This study aimed to evaluate the effect of prebiotic exposure during perinatal and postweaning periods on immune and gut regulations. Mice were fed either a galactooligosaccharides/inulin prebiotic mix-enriched diet or a control diet during the perinatal and/or postweaning periods. Biomarkers related to gut barrier function (SCFA, heat shock proteins, zonula occludens protein-1, and mucin-2) and immune mechanisms (IgA, IgE, IgG1, IgG2a, IL-10, TGF-β, IL-4, IL-17A, and IFN-γ) were analyzed. The milk of dams fed the prebiotic diet was more concentrated in both IgA and TGF-β when prebiotics were introduced during both the perinatal and postweaning periods; IL-10, IgA, and IgG2a were increased in pups; and expression of intestinal markers was more pronounced. Postweaning exposure to prebiotics alone induced higher INF-γ and TGF-β levels, whereas IgA levels fell. Combined exposure periods (perinatal/postweaning) to prebiotics increased tolerance-related immunoglobulins in pups and reinforced gut barrier functions.

Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice

Food allergies affect 4–8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice.