Background: Intestinal barrier dysfunction may lead to a break in tolerance and development of food allergy (FA). There is contradictory evidence on whether intestinal permeability (IP) is altered in IgE-mediated FA. Thus, we sought to determine whether IP differed between children with eczema who did (FA group) or did not (atopic controls, ACs) develop FA and whether peanut sensitization, allergy and early introduction impacted IP using serum biomarkers zonulin, soluble CD14, and Intestinal Fatty Acid Binding Protein among randomly selected participants enrolled in the Learning Early About Peanut allergy trial. Methods: FA group was defined as having at least one FA at either baseline (4-11 months) or 60 months of age (V60). ACs had eczema at baseline and no FA at either visit. Serum IP markers (sIPMs) were measured by ELISA at baseline and V60 and their relationship with clinical characteristics of participants were analyzed using parametric tests and linear regression models. Results: We evaluated 237 FA subjects and 76 ACs. sIPM levels were similar in FA subjects and ACs at baseline and V60. Age when the child first developed any FA (<1 year vs >1 year), eczema severity, peanut sensitization, peanut allergy, and early peanut introduction were not statistically significantly associated with sIPM levels. Total IgE and eosinophil levels, peanut-specific IgE, IgG4 and IgG4/IgE ratio were not correlated with sIPM levels. Conclusion: No differences in sIPMs were detected to support altered IP in infants with FA compared to ACs or following early peanut introduction among peanut sensitized children.

Background: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort. Methods: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales and were generally well exclusively breastfed babies recruited at 3 months old and followed up until 11 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12m, 36m and 7-11y. Results: The prevalence of PA was 2.1% with only 1 child having PA resolution at 7-11y. PA children had larger SPT size, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p<0.001) compared to PS children at 36m and 7-11y. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant at both 36m and 7-11y (p<0.001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36m. New PA children had increased SPT and peanut-sIgE from 36m to 7-11y, but MAT remained low. PS children had low biomarkers across time. Conclusions: In this cohort, few children outgrow or develop new PA between 36m and 7-11y. Children with PA have significantly higher SPT, peanut-sIgE, Ara h 2-sIgE and MAT compared to PS children, evident from 12-36m of age.

Food Allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of 1) an intact epidermal barrier to prevent epicutaneous antigen presentation, 2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and 3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

Food Allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of 1) an intact epidermal barrier to prevent epicutaneous antigen presentation, 2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and 3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

Medical Algorithm: Early Introduction of Food Allergens in High Risk PopulationsHelen R Fisher,1,2 Gideon Lack,1,2,3 Graham Roberts,4,5,6 Henry T Bahnson,7 George Du Toit.1,2,31Paediatric Allergy Group, Department of Women and Children’s Heath, School of Life Course Sciences, King’s College London, London, United Kingdom2Paediatric Allergy Group, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom.3Children’s Allergy Service, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom.4The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, UK.5NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.6Faculty of Medicine, Clinical and Experimental Sciences, Human Development in Health Academic Units, University of Southampton, Southampton, UK.7Immune Tolerance Network, Benaroya Research Institute, Seattle, WashingtonCorresponding Authour:Professor George Du ToitPaediatric AllergyBlock B, South WingSt Thomas’ HospitalLondonSE1 7EHTel: 0207 188 9784Email: George.dutoit@gstt.nhs.ukWord Count: 602Tables: 0Figures: 1Oral Tolerance Induction (OTI) is the only RCT-proven effective intervention for preventing childhood food allergy.(1) OTI to peanut is effective in a general population, with the greatest effect, 81% RRR, noted in the high-risk population.(2) OTI also reduced egg allergy in the general population.(1) Many governmental and allergy societies now recommend introducing peanut in infancy and some suggest other foods, such as well-cooked egg, are also introduced. Choosing which infants should undergo OTI, at what age, to which foods, and under which circumstances is critical for successful OTI prevention in populations where food allergy is a public health concern.Infants with eczema are at increased risk of food allergy but infants from the general population are also at risk and contribute most cases at a population level. Risk of food sensitisation or food allergy increase with age; OTI is most likely to be successful when started in early infancy. Oral tolerance induction from 4 months of age, when completed using standard foods, is safe for nutrition, growth and general child health outcomes (3). Commencing multiple food OTI at 4 months of age, has no detrimental effect on established breastfeeding.(4) All children should adopt a diverse weaning diet, including allergenic foods such as well-cooked egg and peanut, as soon as weaning commences. High risk children should not delay weaning but start weaning and actively include peanut and well-cooked egg, as soon as developmentally ready; usually at about 4 months of age (Fig 1).A 2g/week dosing regime of peanut and well-cooked egg in early infancy is more effective in inducing oral tolerance than later introduction.(5) A lower dosing regime has not been shown to be effective in preventing allergy but, importantly, does not increase allergy risk above that of children who introduce allergenic foods in later infancy.(4) There are limited data regarding the efficacy of OTI to other allergenic foods, or the dose required.(1) All infants should aim to consume about 2g of peanut protein and well-cooked egg per week; parents of high-risk infants should give these amounts more diligently. Given the benefit observed for peanut and egg, it is reasonable for all weaning infants to additionally incorporate 2g of other common and nutritious food allergens; cow’s milk (e.g. as yoghurt), wheat, fish and sesame.Whether children should undergo allergy testing and/or have their first feed of peanut under medical supervision is contested. This cautious approach, potentially requiring large numbers of children to access specialist allergy care, must be balanced against the risks of severe allergic reaction, particularly as most allergic reactions occur on first oral exposure. RCTs of OTI using whole foods had no cases of anaphylaxis on first exposure (4, 6) although anaphylaxis has occurred to OTI using pasteurised whole egg powder.(7) Children with no personal food allergy risk factors do not require testing prior to, or medical supervision during, their first consumption of peanut or well-cooked egg. Children with moderate to severe eczema, or with an existing food allergy should undergo allergy testing +/- OFC at a specialist allergy centre(8), if doing so would not cause undue delay to OTI. It is likely that rapid access to allergy services will be further compromised as a consequence of the COVID-19 pandemic. It may however be that access to SpIgE is available through GP or paediatrician which, if ≥0.35KiU/L, will require referral for OFC. If negative (<0.35KiU/L) the food may be introduced at home following precautionary measures for the first feed: child is well; parent is aware of the signs of IgE mediated reaction has, access to medical support if required and age-appropriate form of the food is given incrementally (Figure 1).