United Graduate School of Agricultural Science, Gifu University, Gifu, Japan.
Graduate School of Natural Science and Technology, Gifu University, Gifu, Japan.
Front Immunol. 2019 Dec 19;10:2979. doi: 10.3389/fimmu.2019.02979. eCollection 2019.
Dietary fiber, with intake of soluble fibers in particular, has been reported to lower the risk for developing inflammatory bowel diseases (IBD). This is at least partly attributable to the fermentation of dietary fiber by the colonic microbiota to produce short chain fatty acids. Pectin, a widely consumed soluble fiber, is known to exert a protective effect in murine models of IBD, but the underlying mechanism remains elusive. Apart from having a prebiotic effect, it has been suggested that pectin direct influences host cells by modulating the inflammatory response in a manner dependent on its neutral sugar side chains. Here we examined the effect of the side chain content of pectin on the pathogenesis of experimental colitis in mice. Male C57BL/6 mice were fed a pectin-free diet, or a diet supplemented with characteristically high (5% orange pectin) or low (5% citrus pectin) side chain content for 10-14 days, and then administered 2,4,6-trinitrobenzene sulfonic acid or dextran sulfate sodium to induce colitis. We found that the clinical symptoms and tissue damage in the colon were ameliorated in mice that were pre-fed with orange pectin, but not in those pre-fed with citrus pectin. Although the population of CD4Foxp regulatory T cells and CD4RORγt inflammatory T cells in the colon were comparable between citrus and orange pectin-fed mice, colonic interleukin (IL)-1β and IL-6 levels in orange pectin-fed mice were significantly decreased. The fecal concentration of propionic acid in orange pectin-fed mice was slightly but significantly higher than that in control and citrus pectin-fed mice but the cecal concentration of propionic acid after the induction of TNBS colitis was comparable between orange and citrus pectin-fed mice. Furthermore, the protective effect of orange pectin against colitis was observed even in mice treated with antibiotics. IL-6 production from RAW264.7 cells stimulated with the toll-like receptor agonist Pam3CSK4 or lipopolysaccharide was suppressed by pre-treatment with orange pectin . Taken together, these results suggest that the side chains of pectin not only augment prebiotic effects but also directly regulate IL-6 production from intestinal host cells in a microbiota-independent fashion to attenuate colitis.
膳食纤维，特别是可溶性膳食纤维的摄入，据报道可以降低炎症性肠病（IBD）的发病风险。这至少部分归因于膳食纤维被结肠微生物群发酵产生短链脂肪酸。果胶是一种广泛食用的可溶性纤维，已知在 IBD 的小鼠模型中具有保护作用，但潜在机制尚不清楚。除了具有益生元作用外，据认为果胶通过调节炎症反应，以依赖其中性糖侧链的方式直接影响宿主细胞。在这里，我们研究了果胶侧链含量对实验性结肠炎发病机制的影响。雄性 C57BL/6 小鼠用无果胶饮食或补充特征性高（5%橙果胶）或低（5%柑橘果胶）侧链含量的饮食喂养 10-14 天，然后用 2,4,6-三硝基苯磺酸或葡聚糖硫酸钠诱导结肠炎。我们发现，预先用橙果胶喂养的小鼠的临床症状和结肠组织损伤得到改善，但预先用柑橘果胶喂养的小鼠则不然。尽管柑橘果胶和橙果胶喂养的小鼠结肠中 CD4Foxp 调节性 T 细胞和 CD4RORγt 炎症性 T 细胞的数量相当，但橙果胶喂养的小鼠结肠中白细胞介素（IL）-1β和 IL-6 水平显著降低。橙果胶喂养的小鼠粪便丙酸浓度略高，但与对照和柑橘果胶喂养的小鼠相比有显著差异，但橙果胶和柑橘果胶喂养的小鼠在诱导 TNBS 结肠炎后盲肠丙酸浓度相当。此外，即使在使用抗生素治疗的小鼠中，橙果胶对结肠炎的保护作用也得到了观察。用 TLR 激动剂 Pam3CSK4 或脂多糖刺激 RAW264.7 细胞后，IL-6 的产生被橙果胶预处理抑制。总之，这些结果表明，果胶的侧链不仅增强了益生元的作用，而且还以独立于微生物群的方式直接调节肠道宿主细胞的 IL-6 产生，从而减轻结肠炎。
