Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Clin Exp Allergy. 2009 Dec;39(12):1842-51. doi: 10.1111/j.1365-2222.2009.03326.x. Epub 2009 Sep 3.
Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear.
To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs).
Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex.
The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1 beta), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples.
Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.
在致敏婴儿中，唾液分泌型免疫球蛋白 A（SIgA）水平较高的婴儿比水平较低的婴儿更不容易出现过敏症状。此外，早期定植某些肠道微生物群，如乳杆菌和双歧杆菌属，可能与较少的过敏发展有关。尽管动物和体外研究强调了共生肠道微生物群在免疫系统发育中的作用，但肠道微生物群对婴儿免疫发育的影响尚不清楚。
评估某些肠道微生物群物种的早期定植是否与黏膜和全身免疫反应相关，即唾液 SIgA 以及自发的 Toll 样受体（TLR）2 和 TLR4mRNA 表达和外周血单个核细胞（PBMC）中脂多糖（LPS）诱导的细胞因子/趋化因子反应。
从 64 名瑞典婴儿出生后 1 周、1 个月和 2 个月收集粪便样本，并前瞻性随访至 5 岁。使用针对艰难梭菌、四种双歧杆菌、两组乳杆菌和脆弱拟杆菌的实时 PCR 分析细菌 DNA。在 6 个月和 12 个月以及 2 岁和 5 岁时收集唾液，并使用 ELISA 测量 SIgA。在出生后 12 个月收集 PBMC，使用实时 PCR 分析 TLR2 和 TLR4mRNA 表达。此外，用 LPS 刺激 PBMC，并使用 Luminex 测量细胞因子/趋化因子反应。
早期粪便样本中双歧杆菌的数量与 6 个月时唾液总 SIgA 水平显著相关。早期定植双歧杆菌、乳杆菌组或艰难梭菌不会影响 PBMC 中的 TLR2 和 TLR4 表达。然而，早期定植大量脆弱拟杆菌的婴儿的 PBMC 自发表达的 TLR4mRNA 水平较低。此外，LPS 诱导的炎症细胞因子和趋化因子（如 IL-6 和 CCL4（MIP-1β））的产生与早期粪便样本中脆弱拟杆菌的相对数量呈负相关。
双歧杆菌多样性可能增强黏膜 SIgA 系统的成熟，而脆弱拟杆菌的早期定植可能会下调婴儿期 LPS 的反应性。
