Dataset Information

Prevention of Allergy to a Major Cow's Milk Allergen by Breastfeeding in Mice Depends on Maternal Immune Status and Oral Exposure During Lactation.

ABSTRACT: Background: The high incidence of food allergy in childhood points to the need of elucidating early life factors dictating allergy susceptibility. Here, we aim to address in a mouse model how the exposure to a major cow's milk allergen through breastmilk of mothers with different immune status influences food allergy outcome in offspring. Methods: BALB/cJ future dams were either kept naïve, or sensitized through the oral route using cholera toxin ("orally sensitized") or through the i.p. route using alum ("i.p. sensitized"), or rendered fully tolerant (oral gavage without any adjuvant) to bovine β-lactoglobulin (BLG). After mating with naïve males and delivery, mothers were orally exposed or not to BLG during the whole lactation. Then, eight groups of lactating mothers were considered: naïve, i.p. sensitized, orally sensitized, or tolerant, each exposed or not during lactation. In order to specifically address breastmilk effects on their allergy susceptibility, pups from naïve-synchronized mothers were cross-fostered by the different groups of treated dams and lactating mothers at delivery. In some experiments, mothers kept their own pups to address a possible in utero effect. BLG antigen, BLG-specific antibodies, and BLG-immune complexes were measured in breastmilk from the different lactating mother groups. Allergic sensitization was monitored in 5-weeks old female offspring (n = 7-8/group of lactating mothers) by determining BLG-specific antibodies in plasma and splenocytes cytokine secretion after i.p. injections of BLG/alum. Allergic reaction to oral BLG challenge was evaluated by measuring mMCP1 in plasma. Results: Offspring was protected from one allergic i.p. sensitization when nursed by i.p. sensitized mothers, independently of BLG exposure during lactation. Orally sensitized dams conferred protection in offspring solely when exposed to BLG during lactation, while naïve mothers did not provide any protection upon BLG exposure. The levels of protection correlated with the levels of BLG-specific antibodies and BLG-immune complex in breastmilk. There was a trend for decreased sensitization in offspring breastfed by tolerant and exposed mothers, which was not associated with transfer of specific antibodies through breastmilk. Protection provided by nursing by treated/exposed mothers was not persistent after a boost i.p. injection of the progeny and then did not protect them from an allergic reaction induced at this time point. No additional in utero effects were evidenced. Conclusion: Our study demonstrates the strong potential of breastmilk to modulate immune response to a major cow's milk allergen in the progeny. It highlights the importance of maternal immune status and of her consumption of the allergen during lactation in dictating the outcomes in offspring. This opens perspectives where modulating maternal immune status might increase the chance of cow's milk allergy prevention in breastfed children.

SUBMITTER: Adel-Patient K

PROVIDER: S-EPMC7396486 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Importance:Cow's milk formula (CMF) is used to supplement breastfeeding (BF) at birth without clear clinical evidence to support the practice. Objective:To determine whether avoiding supplementation with CMF at birth can decrease risks of sensitization to cow's milk protein and/or clinical food allergy, including cow's milk allergy (CMA), overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels. Design, Setting, and Participants:The Atopy Induced by Breastfeeding or Cow's Milk Formula (ABC) trial, a randomized, nonblinded clinical trial, began enrollment October 1, 2013, and completed follow-up May 31, 2018, at a single university hospital in Japan. Participants included 330 newborns at risk for atopy; of these, 312 were included in the analysis. Data were analyzed from September 1 through October 31, 2018. Interventions:Immediately after birth, newborns were randomized (1:1 ratio) to BF with or without amino acid-based elemental formula (EF) for at least the first 3 days of life (BF/EF group) or BF supplemented with CMF (?5 mL/d) from the first day of life to 5 months of age (BF plus CMF group). Main Outcomes and Measures:The primary outcome was sensitization to cow's milk (IgE level, ?0.35 allergen units [UA]/mL) at the infant's second birthday. Secondary outcomes were immediate and anaphylactic types of food allergy, including CMA, diagnosed by oral food challenge test or triggered by food ingestion, with food-specific IgE levels of at least 0.35 UA/mL. Subgroup analysis was prespecified by tertiles of serum 25(OH)D levels at 5 months of age. Results:Of the 312 infants included in the analysis (160 female [51.3%] and 152 male [48.7%]), 151 of 156 (96.8%) in the BF/EF and BF plus CMF groups were followed up until their second birthday. The primary outcome occurred in 24 infants (16.8%) in the BF/EF group, which was significantly fewer than the 46 infants (32.2%) in the BF plus CMF group (relative risk [RR], 0.52; 95% CI, 0.34-0.81). The middle tertile of the 25(OH)D subgroup, but not the low and high tertiles, had a significant interaction with the intervention (RR, 0.19; 95% CI, 0.07-0.50; P?=?.02). The prevalence of food allergy at the second birthday was significantly lower in the BF/EF than in the BF plus CMF groups for immediate (4 [2.6%] vs 20 [13.2%]; RR, 0.20; 95% CI, 0.07-0.57) and anaphylactic (1 [0.7%] vs 13 [8.6%]; RR, 0.08; 95% CI, 0.01-0.58) types. Conclusions and Relevance:The evidence suggests that sensitization to cow's milk and food allergy, including CMA and anaphylaxis, are primarily preventable by avoiding CMF supplementation for at least the first 3 days of life. Trial Registration:http://umin.ac.jp Identifier: UMIN000011577.

Project description:BackgroundCow's milk is a food allergen of public health importance both in the United States and globally. Its natural history and epidemiology have been most studied among infants and young children, but the public health burden it places on adults and older pediatric populations remains unclear. This study comprehensively characterizes the US population-level burden of cow's milk allergy (CMA), including its prevalence, severity, health care utilization, psychosocial impact, natural history, and other associated factors-including ability to tolerate extensively heated milk products-within a large, nationally-representative survey sample of US households.MethodsA cross-sectional survey was administered via web and telephone. Population level inference was based on data collected from participants recruited from National Opinion Research Center (NORC) at the University of Chicago's probability-based AmeriSpeak panel. Established dual-sample complex survey calibration methods were used to augment this sample with additional participants recruited through Survey Sampling International to increase the precision of the resulting estimates. In total, surveys were administered to a nationally representative sample of 51 819 US households from October 1, 2015, through September 31, 2016. Self-report responses from 40 453 adults and parent-proxy report for 38 408 children were analyzed.ResultsAnalyzing survey responses from 78 851 individuals, an estimated 4.7% (95% CI, 4.4%-4.9%) of the US population reported current CMA, whereas 1.9% (95% CI, 1.8%-2.1%) met symptom-report criteria for convincing IgE-mediated allergy. An estimated 0.9% (95% CI, 0.8%-1.0%) had CMA that met convincing symptom-report criteria and was physician diagnosed. Female and White respondents were more likely to report outgrowing CMA relative to males and those reporting other races and ethnicities. Individuals with CMA who reported tolerance to baked milk products were less likely to report severe reaction histories (33.5% vs 42.7%; p = .03), a lifetime history of food allergy-related emergency department visits (43.4% vs. 55.8%; p = .005), and treating a milk-allergic reaction with epinephrine (10.6 vs. 18.9%; p = .003). These individuals also exhibited less psychosocial burden on the validated Food Allergy Independent Measure (FAIM) than their counterparts with CMA who were allergic to baked forms of milk.ConclusionThese data indicate a discrepancy in reported rates of allergy to cow's milk among the US general population ranging from approximately 1 in 20 with reported CMA to fewer than 1 in 50 with physician-confirmed CMA. However, they suggest a substantial population-level burden of CMA, including substantial healthcare utilization, psychosocial burden and nutritional impacts-particularly among the approximately 30% of individuals with CMA who cannot tolerate baked forms of milk.

Dataset Information

Prevention of Allergy to a Major Cow's Milk Allergen by Breastfeeding in Mice Depends on Maternal Immune Status and Oral Exposure During Lactation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets