Toomer Ondulla T, Ferguson Martine, Pereira Marion, Do Andrew, Bigley Elmer, Gaines Dennis, Williams Kristina
U.S. Food and Drug Administration, Laurel, MD 20708, United States.
U.S. Food and Drug Administration, Laurel, MD 20708, United States.
Immunobiology. 2014 May;219(5):367-76. doi: 10.1016/j.imbio.2014.01.003. Epub 2014 Jan 18.
Neonatal to early childhood is the critical period for establishing a balance of T helper 1 (Th1) versus T helper 2 (Th2) cellular immunity within the gut, which is strongly influenced by the source and establishment of gut microflora. Probiotic administration has been shown to attenuate Th2-biased cellular immunity and predisposition to food allergies. To test this hypothesis we provided ad libitum a probiotic-supplemented (Primalac 454 Feed Grade Microbials) or control diet to lactating dams with suckling pups and weaned pups until 10 weeks of age. Weaned mice were sensitized/challenged with egg allergen ovalbumin, saline or adjuvant at 6, 8 and 10 weeks of age. At 3, 6, 8 and 10 weeks, fecal samples were collected for microbial analysis, while blood samples were analyzed for ovalbumin-IgE and total plasma IgE levels. At termination, splenic T helper cell lymphocyte population subtypes were determined using FACS analysis and Th1/Th2/Th17 gene expression by PCR array. At 21 days of age, pups suckled by lactating dams fed the probiotic supplemented diet had significantly enhanced Lactobacillus acidophilus fecal counts compared to controls. Moreover, mice fed the probiotic supplemented diet had enhanced splenic naturally occurring and induced regulatory T cell populations, enhanced TGFβ gene expression and reduced expression of allergic mediator IL13 compared to controls. These results provide evidence that early probiotic supplementation may provide host protection from hypersensitivity reactions to food allergens by attenuating food allergen inflammatory responses.
从新生儿期到幼儿期是在肠道内建立辅助性T细胞1(Th1)与辅助性T细胞2(Th2)细胞免疫平衡的关键时期,这一平衡受到肠道微生物群的来源和建立的强烈影响。已证明给予益生菌可减弱以Th2为主的细胞免疫以及食物过敏的易感性。为了验证这一假设,我们随意给哺乳母鼠及其哺乳幼崽和断奶幼崽提供补充了益生菌(Primalac 454饲料级微生物)的饮食或对照饮食,直至幼崽10周龄。断奶小鼠在6、8和10周龄时用卵清蛋白过敏原、生理盐水或佐剂进行致敏/激发。在3、6、8和10周时,采集粪便样本进行微生物分析,同时分析血液样本中的卵清蛋白-IgE和总血浆IgE水平。在实验结束时,使用流式细胞术分析确定脾脏辅助性T细胞淋巴细胞群体亚型,并通过PCR阵列分析Th1/Th2/Th17基因表达。在21日龄时,与对照组相比,由喂食补充了益生菌饮食的哺乳母鼠哺乳的幼崽粪便中嗜酸乳杆菌计数显著增加。此外,与对照组相比,喂食补充了益生菌饮食的小鼠脾脏中天然存在的和诱导产生的调节性T细胞群体增加,TGFβ基因表达增强,过敏介质IL13的表达降低。这些结果证明,早期补充益生菌可能通过减弱食物过敏原炎症反应为宿主提供对食物过敏原超敏反应的保护。