1 Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health, Sichuan University and Healthy Food Evaluation Research Center, Chengdu 610041, Sichuan, China P.R.
2 West China Second University Hospital/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Sichuan University, Chengdu 610041, Sichuan, China P.R.
Benef Microbes. 2018 Sep 18;9(5):815-828. doi: 10.3920/BM2018.0005. Epub 2018 Jun 11.
This study aimed to demonstrate whether exposure to bifidobacteria during early life influences immunity and alleviates the risk of immunoglobulin E (IgE)-mediated allergies in adulthood. BALB/c neonatal mice (n=54) were administered with a lyophilised cell preparation of Bifidobacterium bifidum TMC3115 (TMC3115) for 3 weeks. Following the intervention, the mice were immunised with intraperitoneal ovalbumin (OVA). The morphology and function of the intestinal epithelium were determined using histopathological examinations. Intestinal microbiota was detected using quantitative PCR and characterised using next-generation sequencing of 16S rRNA genes from faecal DNA. Caecal short-chain fatty acids (SCFAs) were measured using gas chromatography-mass spectrometry. Serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and immunoglobulin E (IgE) and the percentage of splenic CD4+ T cells were examined using enzyme-linked immunosorbent assay and flow cytometry, respectively. TMC3115 did not significantly affect body weight, and cause any severe systemic inflammation or other clinical symptoms among the neonatal or adult mice, although the crypt depths and Muc2-positive cells in some intestinal segments of neonatal mice were significantly lower than control. Oral TMC3115 administration significantly increased faecal microbial diversity, relative abundance of Bacteroidetes and caecal SCFAs production in neonatal mice. Following the intervention, neonatal mice treated with TMC3115 exhibited less increase in serum IgE levels induced by OVA in adults and significantly higher TNF-α and IL-10 levels than in control. Our findings indicate that the oral administration of bifidobacteria, particularly certain strains, such as TMC3115, during early life could alleviate the risk of IgE-mediated allergies in adult host animals. Modifications of intestinal microbiota, SCFAs metabolism and anti-inflammatory cytokine IL-10 production by bifidobacteria may at least in part be a key mechanism underlying the effect of bifidobacteria on the IgE-mediated immune sensitivity of hosts to attacks by allergens at both neonatal and adult stages.
本研究旨在证明生命早期接触双歧杆菌是否会影响免疫功能，并降低成年后免疫球蛋白 E（IgE）介导过敏的风险。BALB/c 新生小鼠（n=54）给予冻干双歧杆菌 TMC3115（TMC3115）细胞制剂 3 周。干预后，用腹腔内卵清蛋白（OVA）免疫小鼠。通过组织病理学检查确定肠道上皮的形态和功能。通过定量聚合酶链反应检测肠道微生物群，并通过粪便 DNA 16S rRNA 基因的下一代测序进行特征分析。通过气相色谱-质谱法测量盲肠短链脂肪酸（SCFA）。使用酶联免疫吸附测定法检测血清肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-10 和免疫球蛋白 E（IgE）水平，通过流式细胞术检测脾 CD4+T 细胞的百分比。TMC3115 对新生或成年小鼠的体重没有显著影响，也不会导致任何严重的全身炎症或其他临床症状，尽管新生小鼠某些肠道段的隐窝深度和 Muc2 阳性细胞明显低于对照组。口服 TMC3115 给药可显著增加新生小鼠粪便微生物多样性、拟杆菌门相对丰度和盲肠 SCFA 产生。干预后，TMC3115 处理的新生小鼠在成年时对 OVA 诱导的血清 IgE 水平增加幅度较小，且 TNF-α和 IL-10 水平明显高于对照组。我们的研究结果表明，生命早期口服双歧杆菌，特别是某些菌株，如 TMC3115，可降低成年宿主动物 IgE 介导过敏的风险。双歧杆菌对肠道微生物群、SCFA 代谢和抗炎细胞因子 IL-10 产生的调节至少部分是双歧杆菌对宿主 IgE 介导的对过敏原敏感性的影响的关键机制，这种影响在新生和成年阶段均可观察到。
