Psyllium Fiber Protects Against Colitis Via Activation of Bile Acid Sensor Farnesoid X Receptor.
Psyllium Fiber Protects Against Colitis Via Activation of Bile Acid Sensor Farnesoid X Receptor.
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DOI：
10.1016/j.jcmgh.2023.02.007
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发表时间：
2023
影响因子：
7.2
通讯作者：
Gewirtz, Andrew T.
中科院分区：
文献类型：
--
作者：
Bretin, Alexis;Zou, Jun;San Yeoh, Beng;Ngo, Vu L.;Winer, Shawn;Winer, Daniel A.;Reddivari, Lavanya;Pellizzon, Michael;Walters, William A.;Patterson, Andrew D.;Ley, Ruth;Chassaing, Benoit;Vijay-Kumar, Matam;Gewirtz, Andrew T.
富含纤维的食物有助于健康，但其作用机制仍不明确。对小鼠的纤维类型进行筛选，发现木耳具有独特的能力改善两种慢性炎症状态，即代谢综合征和结肠炎。我们试图确定后者的作用机制。小鼠被喂以谷物为基础的食物，这种食物天然富含纤维或成分定义的饮食，富含半纯化的纤维。对小鼠进行了基础研究和化学诱导和T细胞转移性结肠炎模型的研究。根据临床类型、组织病理学、形态学和免疫学参数的显示，相对于所有测试的饮食，食用富含木耳的成分限定的饮食的小鼠对葡聚糖硫酸钠和T细胞转移诱导的结肠炎都有显著的保护作用。这种保护与肠道微生物群的明显基础变化有关，但与发酵无关，而且在拥有最小微生物区系的小鼠身上保持不变(即改变了舍德勒菌群)。转录分析显示，木耳诱导调节胆汁酸(BA)分泌的基因表达，这表明木耳与BA结合的已知能力可能有助于其预防结肠炎的能力。正如预期的那样，木耳导致粪便BA水平升高，反映它们从肠-肝循环中被清除，但与BA残留的胆碱胺形成鲜明对比的是，增加了血清BA水平。此外，激活法尼醇X受体(FXR)的BA模拟物的使用，以及FXR基因敲除小鼠的使用，表明FXR的激活在木耳对结肠炎的保护中发挥着核心作用。木耳通过改变BA代谢，激活FXR，从而抑制促炎信号，从而预防结肠炎。
Fiber-rich foods promote health, but mechanisms by which they do so remain poorly defined. Screening fiber types, in mice, revealed psyllium had unique ability to ameliorate 2 chronic inflammatory states, namely, metabolic syndrome and colitis. We sought to determine the mechanism of action of the latter. Mice were fed grain-based chow, which is naturally rich in fiber or compositionally defined diets enriched with semi-purified fibers. Mice were studied basally and in models of chemical-induced and T-cell transfer colitis. Relative to all diets tested, mice consuming psyllium-enriched compositionally defined diets were markedly protected against both dextran sulfate sodium- and T-cell transfer-induced colitis, as revealed by clinical-type, histopathologic, morphologic, and immunologic parameters. Such protection associated with stark basal changes in the gut microbiome but was independent of fermentation and, moreover, maintained in mice harboring a minimal microbiota (ie, Altered Schaedler Flora). Transcriptomic analysis revealed psyllium induced expression of genes mediating bile acids (BA) secretion, suggesting that psyllium’s known ability to bind BA might contribute to its ability to prevent colitis. As expected, psyllium resulted in elevated level of fecal BA, reflecting their removal from enterohepatic circulation but, in stark contrast to the BA sequestrant cholestyramine, increased serum BA levels. Moreover, the use of BA mimetics that activate the farnesoid X receptor (FXR), as well as the use of FXR-knockout mice, suggested that activation of FXR plays a central role in psyllium’s protection against colitis. Psyllium protects against colitis via altering BA metabolism resulting in activation of FXR, which suppresses pro-inflammatory signaling.
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影响因子：
4.9
作者：
Miles JP;Zou J;Kumar MV;Pellizzon M;Ulman E;Ricci M;Gewirtz AT;Chassaing B
通讯作者：
Chassaing B
影响因子：
3.7
作者：
Ghebremariam YT;Yamada K;Lee JC;Johnson CL;Atzler D;Anderssohn M;Agrawal R;Higgins JP;Patterson AJ;Böger RH;Cooke JP
通讯作者：
Cooke JP
DOI：
10.1152/ajpgi.00172.2015
发表时间：
2015-10-01
期刊：
American journal of physiology. Gastrointestinal and liver physiology
影响因子：
--
作者：
Chassaing B;Miles-Brown J;Pellizzon M;Ulman E;Ricci M;Zhang L;Patterson AD;Vijay-Kumar M;Gewirtz AT
通讯作者：
Gewirtz AT
影响因子：
30.3
作者：
Karasov TL;Almario J;Friedemann C;Ding W;Giolai M;Heavens D;Kersten S;Lundberg DS;Neumann M;Regalado J;Neher RA;Kemen E;Weigel D
通讯作者：
Weigel D
影响因子：
30.3
作者：
Schroeder BO;Birchenough GMH;Ståhlman M;Arike L;Johansson MEV;Hansson GC;Bäckhed F
通讯作者：
Bäckhed F