Clostridium butyricum CGMCC0313.1 Protects against Autoimmune Diabetes by Modulating Intestinal Immune Homeostasis and Inducing Pancreatic Regulatory T Cells.
Clostridium butyricum CGMCC0313.1 Protects against Autoimmune Diabetes by Modulating Intestinal Immune Homeostasis and Inducing Pancreatic Regulatory T Cells.
复制标题
丁酸梭菌 CGMCC0313.1 通过调节肠道免疫稳态和诱导胰腺调节 T 细胞来预防自身免疫性糖尿病。
DOI：
10.3389/fimmu.2017.01345
复制
发表时间：
2017
影响因子：
7.3
通讯作者：
Chen YQ
中科院分区：
文献类型：
--
作者：
Jia L;Shan K;Pan LL;Feng N;Lv Z;Sun Y;Li J;Wu C;Zhang H;Chen W;Diana J;Sun J;Chen YQ
最近的证据表明，土著梭菌属物种诱导结肠调节性T细胞（T细胞），肠道淋巴细胞能够在炎症环境中迁移到胰岛。因此，我们推测，补充具有良好特征的益生菌丁酸梭菌CGMCC0313.1（CB 0313.1）可以诱导胰腺炎，从而抑制非肥胖糖尿病（NOD）小鼠中的糖尿病发病率。每天向3至45周龄的雌性NOD小鼠施用CB 0313.1。对照组接受等体积的无菌水。每周测量两次空腹血糖。进行肠道微生物群的焦磷酸测序和肠系膜淋巴结（MLN）、胰腺淋巴结（PLN）、胰腺和脾免疫细胞的流式细胞术以研究CB 0313.1治疗的效果。早期口服CB0313.1可减轻胰岛炎，延迟糖尿病发作，改善能量代谢功能障碍。保护可能涉及增加的T淋巴细胞，重新平衡的Th 1/Th 2/Th 17细胞和肠道，PLN和胰腺中的促炎免疫环境的变化。PLN中的α4β7+（肠道归巢受体）TcR增加表明该机制可能涉及肠道启动的TcR向胰腺的迁移增加。此外，16 S rRNA基因测序显示，CB 0313. 1提高了厚壁菌门/拟杆菌门的比例，丰富了梭菌亚群和丁酸盐产生菌亚群。我们的研究结果为口服CB0313.1预防1型糖尿病的未来临床研究提供了基础。
Recent evidence indicates that indigenous Clostridium species induce colonic regulatory T cells (Tregs), and gut lymphocytes are able to migrate to pancreatic islets in an inflammatory environment. Thus, we speculate that supplementation with the well-characterized probiotics Clostridium butyricum CGMCC0313.1 (CB0313.1) may induce pancreatic Tregs and consequently inhibit the diabetes incidence in non-obese diabetic (NOD) mice. CB0313.1 was administered daily to female NOD mice from 3 to 45 weeks of age. The control group received an equal volume of sterile water. Fasting glucose was measured twice a week. Pyrosequencing of the gut microbiota and flow cytometry of mesenteric lymph node (MLN), pancreatic lymph node (PLN), pancreatic and splenic immune cells were performed to investigate the effect of CB0313.1 treatment. Early oral administration of CB0313.1 mitigated insulitis, delayed the onset of diabetes, and improved energy metabolic dysfunction. Protection may involve increased Tregs, rebalanced Th1/Th2/Th17 cells and changes to a less proinflammatory immunological milieu in the gut, PLN, and pancreas. An increase of α4β7+ (the gut homing receptor) Tregs in the PLN suggests that the mechanism may involve increased migration of gut-primed Tregs to the pancreas. Furthermore, 16S rRNA gene sequencing revealed that CB0313.1 enhanced the Firmicutes/Bacteroidetes ratio, enriched Clostridium-subgroups and butyrate-producing bacteria subgroups. Our results provide the basis for future clinical investigations in preventing type 1 diabetes by oral CB0313.1 administration.
登录
查看更多内容
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
15.9
作者：
HANNINEN, A;TAYLOR, C;MICHIE, SA
通讯作者：
MICHIE, SA
影响因子：
3.7
作者：
Holodniy, Mark;Brown, Sheldon T.;Darbyshire, Janet
通讯作者：
Darbyshire, Janet
影响因子：
7.7
作者：
Hansen, Camilla Hartmann Friis;Krych, Lukasz;Hansen, Axel K.
通讯作者：
Hansen, Axel K.
1型糖尿病中CD8（+）T细胞杀死人β细胞的结构基础。
影响因子：
30.5
作者：
通讯作者：
--