Dietary simple sugars alter microbial ecology in the gut and promote colitis in mice
Dietary simple sugars alter microbial ecology in the gut and promote colitis in mice
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DOI：
10.1126/scitranslmed.aay6218
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发表时间：
2020-10-28
影响因子：
17.1
通讯作者：
Zaki, Hasan
中科院分区：
文献类型：
--
作者：
Khan, Shahanshah;Waliullah, Sumyya;Zaki, Hasan
在西方国家，炎症性肠病（IBD）的患病率较高，这表明西方饮食可能是IBD的危险因素。高糖与许多非传染性疾病有关，是西方饮食的标志，但其在IBD中的作用仍然未知。在这里，我们研究了单糖如葡萄糖和果糖对野生型和Il 10（-/-）小鼠结肠炎发病机制的影响。喂食含10%葡萄糖的饮用水或高糖饮食的野生型小鼠发生葡聚糖硫酸钠诱导的严重结肠炎。与未接受葡萄糖治疗的Il 10（-/-）小鼠相比，高葡萄糖喂养的Il 10（-/-）小鼠也发生了恶化的结肠炎。短期摄入高葡萄糖或果糖不会引发健康肠道的炎症反应，但会显著改变肠道微生物群的组成。特别是，粘液降解细菌Akkermansia muciniphila和Bacteroides fragilis的丰度增加。同时，细菌来源的粘液溶解酶富集，导致糖喂养的野生型和Il 10（-/-）小鼠的结肠粘液层糜烂。当小鼠用抗生素治疗或维持在无菌环境中时，未观察到糖诱导的结肠炎恶化，这表明改变的微生物群在糖诱导的结肠炎发病机制中起着关键作用。此外，来自糖处理小鼠的微生物群定殖的无菌小鼠显示结肠炎易感性增加。总之，这些数据表明，摄入单糖易患结肠炎，并通过调节小鼠肠道微生物群增强其发病机制。
The higher prevalence of inflammatory bowel disease (IBD) in Western countries points to Western diet as a possible IBD risk factor. High sugar, which is linked to many noncommunicable diseases, is a hallmark of the Western diet, but its role in IBD remains unknown. Here, we studied the effects of simple sugars such as glucose and fructose on colitis pathogenesis in wild-type and Il10(-/-) mice. Wild-type mice fed 10% glucose in drinking water or high-glucose diet developed severe colitis induced by dextran sulfate sodium. High-glucose-fed Il10(-/-) mice also developed a worsened colitis compared to glucose-untreated Il10(-/-) mice. Short-term intake of high glucose or fructose did not trigger inflammatory responses in healthy gut but markedly altered gut microbiota composition. In particular, the abundance of the mucus-degrading bacteria Akkermansia muciniphila and Bacteroides fragilis was increased. Consistently, bacteria-derived mucolytic enzymes were enriched leading to erosion of the colonic mucus layer of sugar-fed wild-type and Il10(-/-) mice. Sugar-induced exacerbation of colitis was not observed when mice were treated with antibiotics or maintained in a germ-free environment, suggesting that altered microbiota played a critical role in sugar-induced colitis pathogenesis. Furthermore, germ-free mice colonized with microbiota from sugar-treated mice showed increased colitis susceptibility. Together, these data suggest that intake of simple sugars predisposes to colitis and enhances its pathogenesis via modulation of gut microbiota in mice.