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复杂的膳食多糖可调节肠道免疫功能和微生物群,并促进预防自身免疫性糖尿病。

Complex dietary polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes.

机构信息

Department of Microbiology and Immunology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.

University of Illinois at Chicago, Chicago, IL, USA.

出版信息

Immunology. 2019 May;157(1):70-85. doi: 10.1111/imm.13048. Epub 2019 Mar 7.

Abstract

The dietary supplement and prebiotic values of β-glucan-rich products have been widely recognized and dietary approaches for modulating autoimmunity have been increasingly explored, we assess the impact of oral administration of high-purity yeast β-glucan (YBG) on gut immune function, microbiota and type 1 diabetes (T1D) using mouse models. Oral administration of this non-digestible complex polysaccharide caused a dectin-1-dependent immune response involving increased expression of interleukin-10 (IL-10), retinaldehyde dehydrogenase (Raldh) and pro-inflammatory cytokines in the gut mucosa. YBG-exposed intestinal dendritic cells induced/expanded primarily Foxp3 , IL-10 and IL-17 T cells, ex vivo. Importantly, prolonged oral administration of low-dose YBG at pre-diabetic stage suppressed insulitis and significantly delayed the appearance of T1D in non-obese diabetic (NOD) mice. Further, prolonged treatment with YBG showed increased Foxp3 T-cell frequencies, and a significant change in the gut microbiota, particularly an increase in the abundance of Bacteroidetes and a decrease in the Firmicute members. Oral administration of YBG, together with Raldh-substrate and β-cell antigen, resulted in better protection of NOD mice from T1D. These observations suggest that YBG not only has a prebiotic property, but also an oral tolerogenic-adjuvant-like effect, and these features could be exploited for modulating autoimmunity in T1D.

摘要

富含β-葡聚糖的产品的膳食补充剂和益生元价值已得到广泛认可,并且人们越来越多地探索通过饮食来调节自身免疫。我们使用小鼠模型评估了高纯度酵母β-葡聚糖(YBG)对肠道免疫功能、微生物群和 1 型糖尿病(T1D)的影响。口服这种不可消化的复杂多糖会引起依赖 dectin-1 的免疫反应,涉及肠道黏膜中白细胞介素-10(IL-10)、视黄醛脱氢酶(Raldh)和促炎细胞因子表达增加。YBG 暴露的肠道树突状细胞在体外诱导/扩增主要为 Foxp3+、IL-10+和 IL-17+T 细胞。重要的是,在糖尿病前期阶段延长口服低剂量 YBG 可抑制胰岛炎,并显著延迟非肥胖型糖尿病(NOD)小鼠 T1D 的出现。此外,YBG 的长期治疗显示 Foxp3+T 细胞频率增加,肠道微生物群发生显著变化,特别是拟杆菌门的丰度增加,厚壁菌门成员减少。YBG 与 Raldh 底物和β细胞抗原一起口服给药可使 NOD 小鼠更好地免受 T1D 的侵害。这些观察结果表明,YBG 不仅具有益生元特性,而且具有口服免疫耐受佐剂样作用,这些特性可用于调节 T1D 中的自身免疫。

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