Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency.
Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency.
复制标题
肠道微生物介导的溶血磷脂酰胆碱生成促进肠上皮特异性 Fut2 缺乏症的结肠炎
DOI：
10.1186/s12929-021-00711-z
复制
发表时间：
2021-03-15
影响因子：
11
通讯作者：
Hou X
中科院分区：
文献类型：
--
作者：
Tang X;Wang W;Hong G;Duan C;Zhu S;Tian Y;Han C;Qian W;Lin R;Hou X
先前的研究发现岩藻糖基转移酶2（Fut 2）基因是IBD的危险基因。本研究旨在探讨Fut 2在IBD易感性中的作用机制，为IBD的治疗提供新的策略。使用肠上皮特异性Fut 2敲除（Fut 2 △IEC）小鼠。葡聚糖硫酸钠（DSS）诱导结肠炎。通过16 S rRNA分析评估肠道微生物群的组成和多样性，并通过代谢物分析从小鼠粪便中获得代谢组学结果。进行粪便微生物群移植（FMT）实验以确认肠道微生物群与LPC的关联。用溶血磷脂酰胆碱（LPC）处理WT小鼠，以验证其对结肠炎的影响。UC（UC vs.对照组，P = 0.036）和CD（CD vs.对照组，P = 0.031）患者结肠组织中Fut 2和α-1，2-岩藻糖基化的表达降低。与WT小鼠相比，当用DSS处理时，观察到Fut 2 △IEC小鼠中更严重的肠道炎症和破坏屏障功能。与WT小鼠相比，在Fut 2 △IEC小鼠中观察到下肠道微生物群多样性（p < 0.001）。DSS暴露后，Fut 2 △IEC小鼠肠道细菌多样性和组成发生明显变化，粪中LPC浓度升高。FMT实验显示，接受来自Fut 2 △IEC小鼠的粪便微生物群的小鼠表现出更严重的结肠炎和更高的粪便LPC浓度。相关分析表明，LPC浓度与大肠杆菌、嗜胆汁菌、肠杆菌和戈登杆菌4种细菌呈正相关。此外，LPC在体内外均能促进促炎细胞因子的释放，破坏上皮屏障。结肠Fut 2和α-1，2-岩藻糖基化水平在CD和UC患者中均降低。Fut 2 △IEC小鼠的肠道微生物群在结构和功能上发生了改变，促进了LPC的产生，而LPC被证明会促进炎症并损害上皮屏障。在线版本包含补充材料，可通过10.1186/s12929-021-00711-z获得。
Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD. Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis. The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria—Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo. Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier. The online version contains supplementary material available at 10.1186/s12929-021-00711-z.
登录
查看更多内容
影响因子：
4.6
作者：
Lock JY;Carlson TL;Wang CM;Chen A;Carrier RL
通讯作者：
Carrier RL
DOI：
10.1177/2211068214561025
发表时间：
2015-04
期刊：
Journal of laboratory automation
影响因子：
--
作者：
Srinivasan B;Kolli AR;Esch MB;Abaci HE;Shuler ML;Hickman JJ
通讯作者：
Hickman JJ
影响因子：
30.8
作者：
通讯作者：
--
一种用于大规模检测、鉴定和定量广泛目标代谢物的新型综合方法：在水稻代谢组学研究中的应用。
影响因子：
27.5
作者：
Chen, Wei;Gong, Liang;Luo, Jie
通讯作者：
Luo, Jie
DOI：
10.1038/nrgastro.2017.88
发表时间：
2017-10
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Ni J;Wu GD;Albenberg L;Tomov VT
通讯作者：
Tomov VT