Rekima A, Macchiaverni P, Turfkruyer M, Holvoet S, Dupuis L, Baiz N, Annesi-Maesano I, Mercenier A, Nutten S, Verhasselt V
University of Nice Sophia Antipolis, TIM, EA 6302, Nice, France.
Institute of Biomedical Sciences - University of São Paulo, São Paulo, Brazil.
Clin Exp Allergy. 2017 Apr;47(4):565-576. doi: 10.1111/cea.12864. Epub 2017 Jan 26.
Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence.
We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-β supplementation after weaning would prolong it.
We quantified ovalbumin (OVA) and OVA-specific immunoglobulin levels by ELISA in milk from the EDEN birth cohort. As OVA-specific Ig was found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhoea in their 6- and 13-week-old progeny. In some experiments, a TGF-β-enriched formula was given after weaning.
At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhoea after six and seven OVA challenges vs. 44% and 72% in mice breastfed by naïve mothers (P = 0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA-specific IgE (P < 0.0001). At 13 weeks, although OVA-specific IgE remained low (P = 0.001), diarrhoea occurrence increased to 32% and 46% after six and seven OVA challenges in mice breastfed by OVA-exposed mothers. MMCP1 levels were not significantly inhibited. Supplementation with TGF-β after weaning induced a strong protection in 13-week-old mice breastfed by OVA-exposed mothers compared with mice breastfed by naive mothers (0%, 13% and 32% of diarrhoea at the fifth, sixth and seventh challenges vs. 17, 42 and 78%; P = 0.05, 0.0043 and 0.0017). MMCP1 levels decreased by half compared with control mice (P = 0.02). Prolonged protection was only observed in mice rendered tolerant by breastfeeding and was associated with an improved gut barrier.
In mice, prevention of food allergy by breastfeeding-induced tolerance is of limited duration. Nutritional intervention by TGF-β supplementation after weaning could prolong beneficial effects of breast milk on food allergy prevention.
早期生活中诱导口服耐受是预防食物过敏的一种有前景的方法。其成功需要确定其持续存在所必需的因素。
我们旨在评估小鼠中通过母乳喂养诱导的口服耐受预防过敏的持续时间，以及断奶后口服补充转化生长因子-β（TGF-β）是否会延长该时间。
我们通过酶联免疫吸附测定法（ELISA）对EDEN出生队列的母乳中的卵清蛋白（OVA）和OVA特异性免疫球蛋白水平进行定量。由于在所有样本中均发现了OVA特异性Ig，我们评估了在哺乳期接触OVA的经OVA免疫的小鼠是否可以预防其6周龄和13周龄后代出现过敏性腹泻。在一些实验中，断奶后给予富含TGF-β的配方奶。
在6周龄时，由接触OVA的母亲母乳喂养的小鼠在接受6次和7次OVA激发后，分别只有13%和34%出现腹泻，而由未接触过OVA的母亲母乳喂养的小鼠这一比例分别为44%和72%（P = 0.02和0.01）。这种保护作用与小鼠肥大细胞糜蛋白酶1（MMCP1）水平和OVA特异性IgE水平降低有关（P < 0.0001）。在13周龄时，尽管OVA特异性IgE水平仍然较低（P = 0.001），但由接触OVA的母亲母乳喂养的小鼠在接受6次和7次OVA激发后，腹泻发生率分别增至32%和46%。MMCP1水平未受到显著抑制。与由未接触过OVA的母亲母乳喂养的小鼠相比，断奶后补充TGF-β对由接触OVA的母亲母乳喂养的13周龄小鼠有很强的保护作用（在第5次、第6次和第7次激发时腹泻发生率分别为0%、13%和32%，而未接触过OVA的母亲母乳喂养的小鼠分别为17%、42%和78%；P = 0.05、0.0043和0.0017）。与对照小鼠相比，MMCP1水平降低了一半（P = 0.02）。仅在通过母乳喂养产生耐受的小鼠中观察到了延长的保护作用，且这与肠道屏障改善有关。
在小鼠中，通过母乳喂养诱导耐受预防食物过敏的持续时间有限。断奶后补充TGF-β进行营养干预可以延长母乳对食物过敏预防的有益作用。
