Abstract
Cow’s milk allergy (CMA) prevails in infants and brings increased risk of developing other allergic diseases. Oral administration of specific β-lactoglobulin (BLG)-derived peptides (PepMix) and a specific blend of short- and long-chain fructo-oligosaccharides and Bifidobacterium breve M-16V (FF/Bb) was found to partially prevent CMA development in mice. In this study, we aimed to expand the knowledge on the preventive potential and the underlying mechanisms of this approach. Three-week-old female C3H/HeOuJ mice were orally exposed to PepMix±FF/Bb prior to a 5-week oral sensitization with whole whey and cholera toxin as an adjuvant. The acute allergic skin response was determined after an intradermal challenge with whole whey protein. Following an oral challenge with whey, regulatory T cells (Tregs) in the small intestine lamina propria (SI-LP) and mRNA expression of immune markers in the Peyer’s patches (PP) were investigated. The early impact of PepMix and FF/Bb interventions on the immune system during the oral tolerance (OT) induction phase was investigated after the last OT administration. Pre-exposing mice to PepMix+FF/Bb partially prevented the acute allergic skin response compared to PBS and increased Tregs and activated T cells in the SI-LP compared to sham-sensitized mice. It also increased the mRNA expression of Tbet over GATA3 in the PP of whey-sensitized mice. Directly upon the 6-day OT phase, FF/Bb intervention enhanced cecal content levels of propionic and butyric acid in PepMix-fed mice and the former was positively correlated with Foxp3+ cell numbers in the colon. In the PP of PepMix+FF/Bb-exposed mice, IL-22 mRNA expression increased and IL-10 followed the same tendency, while the Foxp3 expression was increased over GATA3 and RorγT. In the colon, the Tbet mRNA expression increased over GATA3, while IL-22 decreased. In addition, the Foxp3+/GATA3+ and regulatory/effector T cell ratios in the mesenteric lymph nodes and the CD11b+/CD11b− conventional dendritic cells ratio in the SI-LP were increased. In conclusion, the FF/Bb diet facilitates the capacity of the specific BLG-peptides to partially prevent the allergic response after sensitization to whole whey protein, possibly by creating a tolerance-prone environment during the OT phase. Such a dietary intervention might contribute to tailoring successful strategies for CMA prevention.
Highlights
IgE-mediated food allergy is the most prominent cause of early life anaphylaxis [1]
In order to investigate whether the prevention of cow’s milk allergy (CMA) symptoms in the whey allergic mice is associated with changes in regulatory T cells (Tregs) numbers, small intestine (SI)-LP cells were isolated after the challenge phase and analyzed by flow cytometry (Figure 4A)
Mice that received either the whole whey protein, the peptide mixture (PepMix), or the PepMix+FF/Bifidobacterium breve M-16V (Bb) before the sensitization showed increased numbers of CD25+ T cells in the small intestine lamina propria (SI-LP) compared to the sham-sensitized animals (Figure 4B)
Summary
Even though associated with a high rate of natural tolerance and outgrow within the first 5 years of life, cow’s milk allergy (CMA) is the earliest food allergy in infancy and affects 2–3% of children [2]. Both casein and whey proteins from cow’s milk can trigger CMA. Allergenspecific immunotherapy is being developed and can lead to desensitization of patients while on therapy, CMA management in the clinic mainly involves the avoidance of the symptomeliciting food [4] This may affect children’s growth and impair the quality of life of patients and their families [5]
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