Abstract
Oral tolerance is a promising approach for allergy prevention in early life, but it strongly depends on allergen exposure and proper immune environment. Small tolerance-inducing peptides and dietary immunomodulatory components may comprise an attractive method for allergy prevention in at-risk infants. This study aimed to investigate whether early oral exposure to β-lactoglobulin-derived peptides (BLG-peptides) and a specific synbiotic mixture of short- and long- chain fructo-oligosaccharides (scFOS/lcFOS, FF) and Bifidobacterium breve (Bb) M-16V (FF/Bb) can prevent cow’s milk allergy (CMA). Three-week-old female C3H/HeOuJ mice were orally exposed to phosphate buffered saline (PBS), whey protein, or a mixture of four synthetic BLG-peptides combined with a FF/Bb-enriched diet prior to intragastric sensitization with whey protein and cholera toxin. To assess the acute allergic skin response and clinical signs of allergy, mice were challenged intradermally with whole whey protein. Serum immunoglobulins were analyzed after a whey protein oral challenge. Cytokine production by allergen-reactivated splenocytes was measured and changes in T cells subsets in the spleen, mesenteric lymph nodes, and intestinal lamina propria were investigated. Pre-exposing mice to a low dosage of BLG-peptides and a FF/Bb-enriched diet prior to whey protein sensitization resulted in a significant reduction of the acute allergic skin response to whey compared to PBS-pretreated mice fed a control diet. Serum immunoglobulins were not affected, but anaphylactic symptom scores remained low and splenocytes were non-responsive in whey-induced cytokine production. In addition, preservation of the Th1/Th2 balance in the small intestine lamina propria was a hallmark of the mechanism underlying the protective effect of the BLG-peptides–FF/Bb intervention. Prior exposure to BLG-peptides and a FF/Bb-enriched diet is a promising approach for protecting the intestinal Th1/Th2 balance and reducing the allergic response to whole whey protein. Therefore, it might have implications for developing successful nutritional strategies for CMA prevention.
Highlights
Food allergies are becoming a serious health concern worldwide
As a control for maximal oral tolerance induction, animals were pre-exposed to a high dose of whey protein prior to sensitization which resulted in the strongest reduction of the acute allergic skin response as expected (Figure 3A)
The present study demonstrates that a short pre-exposure to a low-dose mixture of four BLG-derived T cell epitopes was able to stimulate the development of oral tolerance to the major cow’s milk protein whey only when combined with a FF/Bifidobacterium breve (Bb) synbiotic diet
Summary
Food allergies are becoming a serious health concern worldwide. Cow’s milk allergy (CMA) is the most prevalent food allergy in infancy and the earliest to occur. Exposure to the intact antigen might result in sensitization or allergic symptoms development in infants at high risk of developing food allergy. Partially hydrolyzed whey proteins were shown to suppress allergic symptoms to cow’s milk in mice [10]. In follow-up studies, a reduced allergic sensitization to the major cow’s milk protein β-lactoglobulin (BLG) was observed when it was coadministered with BLG-derived peptides [13]. Meulenbroek et al further reported that oral pre-exposure to synthetic BLG-derived peptides reduces the allergic skin response to whole whey protein [14]. These studies support the hypothesis that specific protein fragments may be suitable for allergen-specific immunomodulation
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