AUTHOR=Adel-Patient Karine , Guinot Marine , Guillon Blanche , Bernard Hervé , Chikhi Amina , Hazebrouck Stéphane , Junot Christophe 

TITLE=Administration of Extensive Hydrolysates From Caseins and Lactobacillus rhamnosus GG Probiotic Does Not Prevent Cow’s Milk Proteins Allergy in a Mouse Model

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01700

DOI=10.3389/fimmu.2020.01700

ISSN=1664-3224

ABSTRACT=Background: Early nutrition may influence the development of food allergy later in life. In absence of breastfeeding, hydrolysates from cow’s milk proteins (CMP) were indicated as a prevention strategy in at risk infants, but their proof of effectiveness in clinical and pre-clinical studies is still insufficient. Thanks to a validated mouse model, we then assessed specific and nonspecific preventive effects of administration of extensive hydrolysates from caseins (eHC) on the development of food allergy to CMP. The additional nonspecific effect of the probiotic Lactobacillus GG (LGG) was also assessed.
Methods: Groups of BALB/cByJ female mice were pretreated by gavage with either with PBS (control mice), or with non-hydrolyzed milk protein isolate (MPI), eHC or eHC+LGG (eq. of 10 mg of protein/gavage). All mice were then experimentally sensitized to CMP by gavage with CM and the Th2 mucosal adjuvant Cholera toxin. All mice were further chronically exposed to cow’s milk. Sensitization to both caseins and to the non-related whey protein b-lactoglobulin (BLG) was evaluated by measuring specific antibodies in plasma and specific ex vivo Th2/Th1/Th17 cytokine secretion. Elicitation of the allergic reaction was assessed by measuring mMCP1 in plasma obtained after oral food challenge (OFC). Th/Treg cell frequencies in gut associated lymphoid tissue and spleen were analyzed by flow cytometry. Robust statistical procedure combining non-supervised and supervised multivariate analyses and univariate analyses, was conducted to reveal any effect of the pretreatments.
Results: PBS pretreated mice were efficiently sensitized and demonstrated elicitation of allergic reaction after OFC, whereas mice pretreated with MPI were durably protected from allergy to CMP. eHC+/-LGG pretreatments had no protective effect on sensitization to casein (specific) or BLG (non-specific), nor on CMP-induced allergic reaction. Surprisingly, eHC+LGG mice demonstrated significantly enhanced  immune responses after sensitization with CMP. Only some subtle changes were evidenced by flow cytometry.
Conclusions: Neither specific nor nonspecific preventive effects of administration of casein-derived peptides on the development of CMP food allergy were evidenced in our experimental setup. Further studies should be conducted to delineate the mechanisms involved in the immunostimulatory potential of LGG and to clarify its significance in clinic.