State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, P. R. China.
Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Mol Nutr Food Res. 2017 Aug;61(8). doi: 10.1002/mnfr.201601006. Epub 2017 Mar 24.
Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in nonobese diabetic mice.
Female nonobese diabetic mice were weaned to long- and short-chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks. T1D incidence, pancreatic-gut immune responses, gut barrier function, and microbiota composition were analyzed. ITF(l) but not ITF(s) supplementation dampened the incidence of T1D. ITF(l) promoted modulatory T-cell responses, as evidenced by increased CD25 Foxp3 CD4 regulatory T cells, decreased IL17A CD4 Th17 cells, and modulated cytokine production profile in the pancreas, spleen, and colon. Furthermore, ITF(l) suppressed NOD like receptor protein 3 caspase-1-p20-IL-1β inflammasome in the colon. Expression of barrier reinforcing tight junction proteins occludin and claudin-2, antimicrobial peptides β-defensin-1, and cathelicidin-related antimicrobial peptide as well as short-chain fatty acid production were enhanced by ITF(l). Next-generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance and enriched modulatory Ruminococcaceae and Lactobacilli.
Our data demonstrate that ITF(l) but not ITF(s) delays the development of T1D via modulation of gut-pancreatic immunity, barrier function, and microbiota homeostasis.
能够改变肠道屏障和微生物组稳态的膳食纤维会影响 1 型糖尿病（T1D）的进展。在这里，我们旨在比较菊苣根来源的不同可发酵程度的天然可溶性膳食纤维菊糖型果聚糖（ITF）对非肥胖型糖尿病小鼠 T1D 进展的调节作用。
雌性非肥胖型糖尿病小鼠断奶后接受长链和短链 ITF（ITF(l)和 ITF(s)，5%）补充饮食，直至 24 周。分析 T1D 的发生率、胰腺-肠道免疫反应、肠道屏障功能和微生物群组成。ITF(l)而不是 ITF(s)的补充可降低 T1D 的发生率。ITF(l)促进了调节性 T 细胞反应，表现为 CD25 Foxp3 CD4 调节性 T 细胞增加、IL17A CD4 Th17 细胞减少以及胰腺、脾脏和结肠中的细胞因子产生谱发生改变。此外，ITF(l)抑制了结肠中的 NOD 样受体蛋白 3 半胱天冬酶-1-p20-IL-1β炎性小体。ITF(l)增强了屏障强化紧密连接蛋白 occludin 和 claudin-2、抗菌肽 β-防御素-1 和 cathelicidin 相关抗菌肽的表达以及短链脂肪酸的产生。下一代测序分析显示，ITF(l)增强了厚壁菌门/拟杆菌门的比例，达到了抗糖尿病的平衡，并丰富了调节性的 Ruminococcaceae 和 Lactobacilli。
我们的数据表明，ITF(l)而非 ITF(s)通过调节肠道-胰腺免疫、屏障功能和微生物组稳态来延迟 T1D 的发展。
