GLUT5 is a determinant of dietary fructose-mediated exacerbation of experimental colitis
GLUT5 is a determinant of dietary fructose-mediated exacerbation of experimental colitis
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DOI：
10.1152/ajpgi.00059.2021
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发表时间：
2021-08-01
影响因子：
4.5
通讯作者：
Dannenberg, Andrew J.
中科院分区：
文献类型：
--
作者：
Basu, Srijani;Liu, Catherine;Dannenberg, Andrew J.
西方饮食被认为是导致炎症性肠病发病率上升的原因。这导致了一种假设，即果糖，西方饮食的一种成分，可能在炎症性肠病的发病机制中发挥作用。众所周知，高果糖饮食会加剧实验性结肠炎。本研究测试了果糖转运蛋白GLUT 5的表达是否是果糖摄入量增加期间实验性结肠炎严重程度的决定因素，以及回肠炎症是否与克罗恩病中GLUT 5表达改变相关。对基因工程小鼠的研究表明，与Glut 5 +/+小鼠相比，向Glut 5-/-小鼠喂食15 kcal%果糖饮食导致葡聚糖硫酸钠（DSS）诱导的结肠炎更严重。这种效应与结肠果糖水平升高和Glut 5-/-小鼠粪便微生物群的变化有关。重要的是，在Glut 5-/-小鼠中，用广谱抗生素治疗可以防止饮食果糖介导的结肠炎恶化。基因表达分析显示，GLUT 5水平在回肠克罗恩病患者的肠道中降低。此外，GLUT 5水平与这些样本中促炎介质的表达呈负相关。总的来说，这些结果表明，饮食成分（果糖）-宿主基因（GLUT 5）相互作用可以塑造结肠微生物群，从而影响结肠炎的严重程度。这项研究提供了第一个证据，即果糖转运蛋白GLUT 5水平的降低会使果糖喂养后的实验性结肠炎恶化，这是由肠道微生物群的变化介导的。此外，GLUT 5表达在克罗恩氏回肠炎中减少。总的来说，这些研究结果证明了饮食果糖和宿主GLUT 5之间相互作用的重要性，作为结肠微生物群组成和实验性结肠炎严重程度的决定因素。
The Western diet has been suggested to contribute to the rising incidence of inflammatory bowel diseases. This has led to the hypothesis that fructose, a component of the Western diet, could play a role in the pathogenesis of inflammatory bowel diseases. A high-fructose diet is known to exacerbate experimental colitis. This study tested whether the expression of GLUT5, the fructose transporter, is a determinant of the severity of experimental colitis during elevated fructose consumption and whether ileal inflammation is associated with altered GLUT5 expression in Crohn's disease. Studies in genetically engineered mice showed that in comparison to Glut5+/+ mice, feeding a 15 kcal% fructose diet to Glut5-/- mice led to worse dextran sodium sulfate (DSS)-induced colitis. This effect was associated with elevated levels of colonic fructose and a shift in the fecal microbiota in Glut5-/- mice. Importantly, treatment with broad-spectrum antibiotics protected against the worsening of colitis mediated by dietary fructose in Glut5-/- mice. Gene expression analysis revealed that GLUT5 levels are reduced in the intestines of patients with ileal Crohn's disease. Moreover, levels of GLUT5 negatively correlated with expression of proinflammatory mediators in these samples. Collectively, these results demonstrate that dietary constituent (fructose)-host gene (GLUT5) interactions can shape the colonic microbiota, thereby impacting the severity of colitis. NEW & NOTEWORTHY This study provides the first evidence that reduced levels of GLUT5, the fructose transporter, worsen experimental colitis upon fructose feeding, an effect mediated by changes in the gut microbiota. Moreover, GLUT5 expression is reduced in Crohn's ileitis. Overall, these findings demonstrate the importance of interactions between dietary fructose and host GLUT5 as determinants of both the composition of colonic microbiota and severity of experimental colitis.