Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.
Carcinogenesis. 2021 Jun 21;42(6):842-852. doi: 10.1093/carcin/bgab007.
Diet is believed to be an important factor in the pathogenesis of inflammatory bowel disease. High consumption of dietary fructose has been shown to exacerbate experimental colitis, an effect mediated through the gut microbiota. This study evaluated whether dietary alterations could attenuate the detrimental effects of a high-fructose diet (HFrD) in experimental colitis. First, we determined whether the procolitic effects of a HFrD could be reversed by switching mice from a HFrD to a control diet. This diet change completely prevented HFrD-induced worsening of acute colitis, in association with a rapid normalization of the microbiota. Second, we tested the effects of dietary fiber, which demonstrated that psyllium was the most effective type of fiber for protecting against HFrD-induced worsening of acute colitis, compared with pectin, inulin, or cellulose. In fact, supplemental psyllium nearly completely prevented the detrimental effects of the HFrD, an effect associated with a shift in the gut microbiota. We next determined whether the protective effects of these interventions could be extended to chronic colitis and colitis-associated tumorigenesis. Using the azoxymethane/dextran sodium sulfate model, we first demonstrated that HFrD feeding exacerbated chronic colitis and increased colitis-associated tumorigenesis. Using the same dietary changes tested in the acute colitis setting, we also showed that mice were protected from HFrD-mediated enhanced chronic colitis and tumorigenesis, upon either diet switching or psyllium supplementation. Taken together, these findings suggest that high consumption of fructose may enhance colon tumorigenesis associated with long-standing colitis, an effect that could be reduced by dietary alterations.
饮食被认为是炎症性肠病发病机制的一个重要因素。研究表明，高果糖饮食会加重实验性结肠炎，这种作用是通过肠道微生物群介导的。本研究评估了饮食改变是否可以减轻高果糖饮食（HFrD）对实验性结肠炎的有害影响。首先，我们确定了将小鼠从 HFrD 转换为对照饮食是否可以逆转 HFrD 的促结肠炎作用。这种饮食改变完全阻止了 HFrD 引起的急性结肠炎恶化，同时微生物群迅速恢复正常。其次，我们测试了膳食纤维的作用，结果表明，与果胶、菊粉或纤维素相比，车前子壳是保护小鼠免受 HFrD 引起的急性结肠炎恶化最有效的膳食纤维类型。事实上，补充车前子壳几乎完全阻止了 HFrD 的有害作用，这与肠道微生物群的转变有关。接下来，我们确定这些干预措施的保护作用是否可以扩展到慢性结肠炎和结肠炎相关的肿瘤发生。我们首先使用氧化偶氮甲烷/葡聚糖硫酸钠模型表明，HFrD 喂养加重了慢性结肠炎并增加了结肠炎相关的肿瘤发生。使用在急性结肠炎研究中测试的相同饮食改变，我们还表明，通过饮食转换或车前子壳补充，小鼠可以免受 HFrD 介导的慢性结肠炎和肿瘤发生增强的影响。总之，这些发现表明，大量摄入果糖可能会增强与长期结肠炎相关的结肠肿瘤发生，这种作用可以通过饮食改变来减轻。
