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

被引:47
|
作者
Gudi, Radhika [1 ]
Perez, Nicolas [2 ]
Johnson, Benjamin M. [1 ]
Sofi, M. Hanief [1 ]
Brown, Robert [1 ]
Quan, Songhua [2 ,3 ]
Karumuthil-Melethil, Subha [2 ,4 ]
Vasu, Chenthamarakshan [1 ]
机构
[1] Med Univ South Carolina, Coll Med, Dept Microbiol & Immunol, Charleston, SC 29425 USA
[2] Univ Illinois, Chicago, IL USA
[3] Northwestern Univ, Feinberg Sch Med, Dept Radiat Oncol, Chicago, IL 60611 USA
[4] Univ N Carolina, Dept Neurol, Chapel Hill, NC 27515 USA
基金
美国国家卫生研究院;
关键词
autoimmunity; gut microbiota; immune modulation; immune regulation; type; 1; diabetes; yeast; -glucan; CD103(+) DENDRITIC CELLS; ADMINISTERED BETA-GLUCAN; TRANS-RETINOIC ACID; T-CELLS; MACROPHAGE FUNCTION; ORAL INSULIN; DECTIN-1; RESPONSES; IMPACT; SAMPLE;
D O I
10.1111/imm.13048
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The dietary supplement and prebiotic values of -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 -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 -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.
引用
收藏
页码:70 / 85
页数:16
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