Abstract

BackgroundAmino acid‐based formulas (AAFs) are used for the dietary management of cow's milk allergy (CMA). Whether AAFs have the potential to prevent the development and/or symptoms of CMA is not known.ObjectiveThe present study evaluated the preventive effects of an amino acid (AA)‐based diet on allergic sensitization and symptoms of CMA in mice and aimed to provide insight into the underlying mechanism.MethodsC3H/HeOuJ mice were sensitized with whey protein or with phosphate‐buffered saline as sham‐sensitized control. Starting 2 weeks before sensitization, mice were fed with either a protein‐based diet or an AA‐based diet with an AA composition based on that of the AAF Neocate, a commercially available AAF prescribed for the dietary management of CMA. Upon challenge, allergic symptoms, mast cell degranulation, whey‐specific immunoglobulin levels, and FoxP3+ cell counts in jejunum sections were assessed.ResultsCompared to mice fed with the protein‐based diet, AA‐fed mice had significantly lower acute allergic skin responses. Moreover, the AA‐based diet prevented the whey‐induced symptoms of anaphylaxis and drop in body temperature. Whereas the AA‐based diet had no effect on the levels of serum IgE and mucosal mast cell protease‐1 (mMCP‐1), AA‐fed mice had significantly lower serum IgG2a levels and tended to have lower IgG1 levels (P = .076). In addition, the AA‐based diet prevented the whey‐induced decrease in FoxP3+ cells. In sham‐sensitized mice, no differences between the two diets were observed in any of the tested parameters.ConclusionThis study demonstrates that an AA‐based diet can at least partially prevent allergic symptoms of CMA in mice. Differences in FoxP3+ cell counts and serum levels of IgG2a and IgG1 may suggest enhanced anti‐inflammatory and tolerizing capacities in AA‐fed mice. This, combined with the absence of effects in sham‐sensitized mice indicates that AAFs for the prevention of food allergies may be an interesting concept that warrants further research.

Highlights

  • acid‐based formulas (AAFs) are used as an option for the dietary management of cows milk allergy (CMA)

  • Whether AAFs have the potential to prevent allergic sensitization and/or symptoms associated with CMA is not known

  • A murine model of CMA was used to examine the preventive effects of an amino acid (AA) diet on allergic sensitization and clinical symptoms

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Summary

| INTRODUCTION

Cows milk allergy (CMA) is one of the most commonly occurring food allergies in infancy, affecting up to 3% of the children at 1 year of age in developed countries.[1,2] CMA in infancy represents an increasing global health and economic burden, which is caused by an increased prevalence over the last decades, and by an increased persistence, severity, and complexity of the condition.[3,4,5,6] Following ingestion of cows milk, affected children usually present moderate symptoms involving the skin, the gastrointestinal, and/or the respiratory tract, but life‐threatening systemic anaphylaxis may occur.[7,8] cows milk is described as one of the most common foods capable of inducing fatal anaphylactic reactions in infancy.[9,10] In addition to these acute clinical manifestations, CMA in early life can have long‐ lasting effects, including delays in growth and development,[11,12] as well as increased risk of developing atopic diseases later in life.[13,14] strategies to suppress or prevent the development of CMA are of major importance. Hydrolyzed formulas (eHFs) are recommended for infants with mild CMA, whereas for infants with severe CMA and for infants who either do not tolerate eHFs or for whom eHFs fail to resolve CMA symptoms, amino acid‐based formulas (AAFs) are recommended.[17] Besides being nutritionally adequate,[18] AAFs are consistently demonstrated to provide relief and a faster recovery from symptoms of CMA, including gastrointestinal (eg, vomiting and diarrhea) and skin conditions (eg, atopic dermatitis).[11,19,20,21] nutritional intervention with an AAF has been shown to fully normalize the growth of patients with CMA.[22,23] Studies show that intake of AAFs is very well‐tolerated, safe, and has no long‐term effects on protein‐metabolism.[22,23,24,25] In summary, AAFs are proven to be an effective and safe way of dietary management of CMA. The present study evaluated the preventive effects of an AA‐based diet on allergic sensitization and allergic symptoms of CMA, using an extensively validated murine model of orally induced CMA.[31]

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