Food allergies: Novel mechanisms and therapeutic perspectives

Childhood food allergy (FA) rates have rapidly increased with significant direct medical costs for the health care system and even larger costs for the families with a food-allergic child. The possible causes of food allergy become the target of intense scrutiny in recent years. Increasing evidence underline the importance in early life of gut microbiome in the development of allergic diseases. There are a range of factors in the modern environment that may be associated with changes to both the gut microbiome and risk of FA, such as mode of delivery, antibiotic exposure, infant feeding practices, farming environment, and country of origin. Knowledge of the relationship between early life gut microbiome and allergic diseases may facilitate development of novel preventive and treatment strategies. Based on our current knowledge, there are no currently available approved therapies for food allergy. More studies are needed to evaluate the safety and efficacy of allergen-specific and allergen-nonspecific approaches, as well as combination approaches

The Potential Immunonutritional Role of Parmigiano Reggiano Cheese in Children with Food Allergy

Parmigiano Reggiano (PR) is a ripened cheese with high nutritional value. Throughout ripening the bacteria contained in PR promote an extensive hydrolysis of cow’s milk proteins resulting in peptides that exhibit positive immunoregulatory activities. Additional modulatory activities on immune system are induced by butyrate, a short chain fatty acid widely expressed in PR. These findings suggest a possible immunonutritional role for PR able to stimulate oral tolerance in children with food allergy (FA)

The Impact of Formula Choice for the Management of Pediatric Cow's Milk Allergy on the Occurrence of other Allergic Manifestations: The Atopic March Cohort Study

To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition

Efficacy of a New Hypotonic Oral Rehydration Solution Containing Zinc and Prebiotics in the Treatment of Childhood Acute Diarrhea: A Randomized Controlled Trial

Objective: To evaluate the efficacy of a hypotonic oral rehydration solution (ORS) containing zinc and prebiotics for treatment of acute diarrhea in children. Study design: We conducted a single-blind, prospective, controlled trial including children (age range, 3-36 months) with acute diarrhea randomly assigned to standard hypotonic ORS (group 1) or to new hypotonic ORS containing zinc and prebiotics (group 2). The main outcome was the rate of resolution of diarrhea at 72 hours. Results: A total of 60 children in group 1 (34 male; mean age, 18.58 months; 95% CI, 15.5-21.6) and 59 in group 2 (36 male; mean age, 19.26 months; 95% CI, 15.9-22.6) completed the study protocol. The rate of diarrhea resolution at 72 hours was higher in group 2 (50% versus 72.9%, P = .010). Total ORS intake in the first 24 hours was higher in group 2 (50 mL/kg; 95% CI, 41-59 versus 22 mL/kg; 95% CI, 17-29; P < .001). The mean number of missed working days by the parents of children in group 2 was lower (0.39; 95% CI, 0.08-0.70 versus 1.45; 95% CI 1.02-1.88; P < .001). Fewer patients in group 2 needed adjunctive drugs for the treatment of diarrhea 6/59 versus 19/60, P = .004. No adverse events were observed in either of the two groups. Conclusion: The addition of zinc and prebiotics to ORS limits diarrhea duration in children. Copyright © 2011 Mosby Inc. All rights reserved

Tolerability of a new amino acid-based formula for children with IgE-mediated cow's milk allergy

Amino acid-based formula (AAF) is a relevant dietary strategy for paediatric patients affected by cow's milk allergy (CMA). The present study was designed to evaluate the hypoallergenicity of a new AAF in children with immunoglobulin (Ig)E-mediated CMA

Randomized controlled trial on the influence of dietary intervention on epigenetic mechanisms in children with cow's milk allergy: the EPICMA study

Epigenetic mechanisms could drive the disease course of cow's milk allergy (CMA) and formula choice could modulate these pathways. We compared the effect of two different dietary approaches on epigenetic mechanisms in CMA children. Randomized controlled trial on IgE-mediated CMA children receiving a 12-month treatment with extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG (EHCF + LGG) or with soy formula (SF). At the baseline, after 6 and 12 months of treatment FoxP3 methylation rate and its expression in CD4+ T cells were assessed. At same study points IL-4, IL-5, IL-10, and IFN-γ methylation rate, expression and serum concentration, miRNAs expression were also investigated. 20 children (10/group) were evaluated. Baseline demographic, clinical and epigenetic features were similar in the two study groups. At 6 and 12 months, EHCF + LGG group showed a significant increase in FoxP3 demethylation rate compared to SF group. At the same study points, EHCF + LGG group presented a higher increase in IL-4 and IL-5 and a higher reduction in IL-10 and IFN-γ DNA methylation rate compared to SF group. A different modulation of miR-155, -146a, -128 and -193a expression was observed in EHCF + LGG vs. SF. Dietary intervention could exert a different epigenetic modulation on the immune system in CMA children

Differences in DNA methylation profile of Th1 and Th2 cytokine genes are associated with tolerance acquisition in children with IgE-mediated cow's milk allergy

Epigenetic changes in DNA methylation could regulate the expression of several allergy-related genes. We investigated whether tolerance acquisition in children with immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) is characterized by a specific DNA methylation profile of Th2 (IL-4, IL-5) and Th1 (IL-10, IFN-γ)-associated cytokine genes

The effect of different formulas in children with cow ' s milk allergy on the occurrence of other allergic manifestations and the time of immune tolerance acquisition: The atopic march II study

Background : Recent data suggest that the use of extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG (LGG) (EHCF+LGG) reduces the incidence of other AMs and hastens the development of immune tolerance in children with IgE- mediated cow ' s milk allergy (CMA). To see whether formula choice for CMA treatment could impact the occurrence of other AMs and the time of immune tolerance acquisition. Method : Prospective open non- randomized trial on a cohort of children with a diagnosis of IgE- mediated CMA in the first year of life, already in follow- up. The patients were treated with one of the following formulas: EHCF+LGG, rice hydrolyzed formula (RHF), soy formula (SF), extensively hydrolyzed whey formula (EHWF) or amino- acid based formula (AAF). All subjects were evaluated during a 36 months follow- up. The occurence of AMs (atopic eczema, allergic urticaria, asthma and oculorhinitis) was diagnosed Immune tolerance acquisition was evaluated every 12 month by the result of oral food challenge. Results : A total of 365 subjects completed the study, 73 per group. All children were from families of middle socio- economic status and lived in urban areas. At enrollment, all subjects were in stable clinical conditions without symptoms related to CMA. Demographic and anamnestic features were similar comparing the study cohorts at enrolment. Binomial regression revealed that the estimates of the incidence of the AMs are: EHCF+LGG: 0.22 (Bonferroni corrected 95%CI: 0.09 to 0.34); RHF: 0.52 (Bonferroni corrected 95%CI: 0.37 to 0.67); SF: 0.58 (Bonferroni corrected 95%CI: 0.43 to 0.72); EHWF : 0.51 (Bonferroni corrected 95%CI: 0.36 to 0.66); AAF: 0.77 (Bonferroni corrected 95%CI: 0.64 to 0.89). The incidence of the main outcome in the RHF, SF, EHWF and AAF groups vs the EHCF+LGG group was always higher than the pre- specified absolute difference of 0.25 and significantly higher at the pre- specified alphalevel of 0.0125 ( P - value <= 0.001 in all cases). The acquisition of immune tolerance was significantly higher in the EHCF+LGG group comparing to the other groups. The rate of immune tolerance acquisition for EHCF+LGG groups was (95%CI): at 12 months = 0.41 (0.30 to 0.52); at 24 months = 0.64 (0.53 to 0.75); at 36 months = 0.81 (0.72 to 0.90). Conclusion : The results of the study suggest that EHCF+LGG is superior to other formulas for the prevention of AMs and for the acquisition of immune tolerance in children with CMA

Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy

The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms. Short-chain fatty acids are crucial metabolic products of gut microbiota responsible for many protective effects against food allergy. These compounds are involved in epigenetic regulation of the immune system. These evidences provide a foundation for developing innovative strategies to prevent and treat food allergy. Here, we present an overview on the potential role of gut microbiota as the target of intervention against food allergy