Sa1131 – Lactobacillus Rhamnosus Gg Colonization in Early Life Protects Intestinal Barrier of Offspring and Relieves Anxiety-Like Behavior in Adulthood

Background: Peanut allergy is increasing in prevalence, has no FDA-approved therapy and is associated with an increased risk of fatal food-induced anaphylaxis.We recently described an oral allergy-prone mouse strain identified through the Collaborative Cross (CC), denoted CC027/GeniUnc, that is sensitized and subsequently develops anaphylaxis upon oral exposure to peanut protein without an adjuvant.However, the underlying mechanism of allergy development in this model is not known.Methods: CC027/GeniUnc mice were co-housed with other CC strains and C3H/HeJ, BALB/cJ, and C57Bl/6J mice for stool microbiome studies.Stool was collected at baseline and after oral sensitization with crude peanut extract (CPE).Weekly oral gavage with 2 mg CPE for 3 weeks followed by oral gavage with 5 mg CPE in week four established sensitization.One week later, sensitized mice were challenged by oral gavage with 10 mg CPE, and body temperature was monitored every 15 minutes for 60 minutes via rectal temperature probe.For intestinal barrier studies, FITC-dextran 4 kDa (FD4) with or without CPE was administered by oral gavage, and plasma was collected at various timepoints for fluorescence measurement.Results: Peanut protein-sensitized CC027/GeniUnc mice have decreased stool total IgA and increased stool total IgG compared to that of C3H/HeJ and BALB/cJ mice.Stool microbial composition from naïve CC027/ GeniUnc mice clustered independently from that of naïve non-oral allergy-prone mouse strains and peanut-sensitized CC027/GeniUnc mice.Interestingly, stool microbial composition alpha-and beta-diversity were increased in CC027/GeniUnc mice.Sensitized CC027/ GeniUnc mice demonstrated increased plasma FD4 concentration that further increased with the addition of CPE.Conclusions: Oral peanut allergy-prone CC027/GeniUnc mice demonstrate unique gastrointestinal microbial communities that are altered by peanut exposure.Peanut exposure also induced less stool IgA and increased intestinal permeability in CC027/GeniUnc mice.Together, these peanut-induced changes are associated with oral sensitization and development of peanut allergy in CC027/GeniUnc mice.