Department of Nutritional Medicine, University of Hohenheim. Stuttgart, Germany.
Medical Clinic 1, Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen, Germany.
Am J Physiol Gastrointest Liver Physiol. 2019 Oct 1;317(4):G493-G507. doi: 10.1152/ajpgi.00297.2018. Epub 2019 Aug 14.
Genetically modified mice have been successfully used as models for inflammatory bowel diseases; however, dietary effects were poorly examined. Here, we studied the impact of particular nutrients and supplements on gut functions related to the knockout of the epithelial caspase-8 gene. Caspase-8 knockout (Casp8) and control (Casp8) mice were fed for 4 wk a control diet (CD) enriched with 10% inulin (CD-Inu) or 5% sodium butyrate (CD-But) while having free access to plain water or water supplemented with 30% fructose (+F). Body weight changes, intestinal inflammation, and selected markers for barrier function and of liver steatosis were assessed. Casp8 mice developed ileocolitis accompanied by changes in intestinal barrier morphology and reduced expression of barrier-related genes such as mucin-2 ( and defensins in the ileum and in the colon. Casp8 mice fed a CD also showed impaired body weight gain compared with Casp8 mice, which was even more pronounced in mice receiving water supplemented with fructose. Furthermore, we observed a marked liver steatosis and inflammation in some but not all Casp8 mice under a CD, which was on average similar to that observed in control mice under a fructose-rich diet. Hepatic lipid accumulation, as well as markers of ileal barrier function, but not intestinal pathohistology or body weight loss, were attenuated by diets enriched with inulin or butyrate, especially in the absence of fructose supplementation. Our data show that ileocolitis, barrier dysfunction, and malassimilation in Caspase-8 knockout mice can be partially attenuated by oral inulin or butyrate supplementation. Genetic mouse models for ileocolitis are important to understand inflammatory bowel disease in humans. We examined dietetic factors that might aggravate or attenuate ileocolitis and related pathologies in such a model. Deletion of the caspase-8 gene results not only in ileocolitis but also in gut barrier dysfunction, liver steatosis, and malassimilation, which can be partially attenuated by oral inulin or sodium butyrate. Our data indicate that diet modifications can contribute to disease variability and therapy.
基因修饰小鼠已成功用作炎症性肠病模型；然而，饮食的影响尚未得到充分研究。在此，我们研究了特定营养素和补充剂对上皮细胞半胱氨酸蛋白酶-8 基因敲除相关肠道功能的影响。给予 caspase-8 基因敲除（Casp8）和对照（Casp8）小鼠 4 周对照饮食（CD），其中富含 10%菊粉（CD-Inu）或 5%丁酸钠（CD-But），同时自由饮用普通水或添加 30%果糖的水（+F）。评估体重变化、肠道炎症以及屏障功能和肝脂肪变性的标志物。Casp8 小鼠发展为回结肠炎，伴有肠道屏障形态变化和屏障相关基因如粘蛋白-2（ 和防御素在回肠和 结肠中的表达减少。与接受果糖补充水的 Casp8 小鼠相比，接受 CD 的 Casp8 小鼠的体重增加也受到损害，这种情况在接受果糖补充水的小鼠中更为明显。此外，我们在一些但不是所有接受 CD 的 Casp8 小鼠中观察到明显的肝脂肪变性和炎症，平均而言，这种情况与接受富含果糖饮食的对照小鼠相似。在没有果糖补充的情况下，富含菊粉或丁酸钠的饮食可减轻肝脂质积累以及回肠屏障功能标志物，但不能减轻肠道组织病理学或体重减轻。我们的数据表明，Caspase-8 基因敲除小鼠的回结肠炎、屏障功能障碍和吸收不良可以通过口服菊粉或丁酸钠来部分缓解。用于回结肠炎的基因修饰小鼠模型对于理解人类炎症性肠病很重要。我们研究了可能加重或减轻这种模型中回结肠炎和相关病理的饮食因素。半胱氨酸蛋白酶-8 基因的缺失不仅导致回结肠炎，还导致肠道屏障功能障碍、肝脂肪变性和吸收不良，这些可通过口服菊粉或丁酸钠部分缓解。我们的数据表明，饮食改变可能有助于疾病的变异性和治疗。
