Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.
University of Toledo Microbiome Consortium, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.
Cell Mol Gastroenterol Hepatol. 2023;15(6):1421-1442. doi: 10.1016/j.jcmgh.2023.02.007. Epub 2023 Feb 23.
BACKGROUND & AIMS: 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.
富含纤维的食物有益于健康，但它们发挥作用的机制仍不清楚。在小鼠中筛选纤维类型表明，车前子具有独特的能力，可以改善 2 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。
用谷物基饲料喂养小鼠，这种饲料天然富含纤维，或用半纯化纤维组成的饮食来丰富饮食。在基础状态和化学诱导及 T 细胞转移结肠炎模型中研究小鼠。
与所有测试的饮食相比，食用富含车前子的组成性定义饮食的小鼠对葡聚糖硫酸钠和 T 细胞转移诱导的结肠炎均有明显的保护作用，表现在临床类型、组织病理学、形态学和免疫学参数上。这种保护与肠道微生物组的明显基础变化有关，但与发酵无关，此外，在携带最小微生物群（即改变的 Schaedler 菌群）的小鼠中也能维持。转录组分析显示车前子诱导了介导胆汁酸（BA）分泌的基因表达，表明车前子已知的结合 BA 的能力可能有助于其预防结肠炎的能力。正如预期的那样，车前子导致粪便 BA 水平升高，反映了它们从肠肝循环中的排出，但与 BA 螯合剂考来烯胺形成鲜明对比的是，血清 BA 水平升高。此外，使用激活法尼醇 X 受体（FXR）的 BA 模拟物以及使用 FXR 敲除小鼠表明，FXR 的激活在车前子预防结肠炎中起着核心作用。
车前子通过改变 BA 代谢来预防结肠炎，从而激活 FXR，抑制促炎信号。
