Background & Aims

The incidence of inflammatory bowel diseases has increased over the last half century, suggesting a role for dietary factors. Fructose consumption has increased in recent years. Recently, a high fructose diet (HFrD) was shown to enhance DSS-induced colitis in mice. The primary objectives of the current study were to elucidate the mechanism(s) underlying the pro-colitic effects of dietary fructose and to determine whether this effect occurs in both microbially-driven and genetic models of colitis.

Methods

Antibiotics and germ-free mice were used to determine the relevance of microbes for HFrD-induced worsening of colitis. Mucus thickness and quality were determined by histological analyses. 16S rRNA profiling, in situ hybridization, metatranscriptomic analyses and fecal metabolomics were used to determine microbial composition, spatial distribution and metabolism. The significance of a HFrD on pathogen and genetic-driven models of colitis was determined using Citrobacter rodentium infection and Il10^-/- mice, respectively.

Results

Reducing or eliminating bacteria attenuated HFrD-mediated worsening of DSS-induced colitis. HFrD feeding enhanced access of gut luminal microbes to the colonic mucosa by reducing thickness and altering the quality of colonic mucus. Feeding a HFrD also altered gut microbial populations and metabolism including reduced protective commensal and bile salt hydrolase-expressing microbes, and increased luminal conjugated bile acids. Administration of conjugated bile acids to mice worsened DSS-induced colitis. The HFrD also worsened colitis in Il10^-/- mice and mice infected with C. rodentium.

Conclusions

Excess dietary fructose consumption has a pro-colitic effect that can be explained by changes in the composition, distribution and metabolic function of resident enteric microbiota.

中文翻译：

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膳食果糖改变与恶化的结肠炎相关的肠道微生物群的组成、定位和代谢。

背景与目标

在过去的半个世纪里，炎症性肠病的发病率有所增加，这表明饮食因素的作用。近年来，果糖消费量有所增加。最近，高果糖饮食 (HFrD) 被证明可以增强 DSS 诱导的小鼠结肠炎。当前研究的主要目的是阐明膳食果糖促结肠炎作用的潜在机制，并确定这种作用是否发生在微生物驱动的结肠炎和遗传模型中。

方法

使用抗生素和无菌小鼠来确定微生物与 HFrD 诱导的结肠炎恶化的相关性。通过组织学分析确定粘液厚度和质量。16S rRNA 分析、原位杂交、宏转录组学分析和粪便代谢组学被用来确定微生物组成、空间分布和代谢。HFrD 对病原体和遗传驱动的结肠炎模型的重要性分别使用柠檬酸杆菌感染和Il10 ^-/-小鼠确定。

结果

减少或消除细菌减弱了 HFrD 介导的 DSS 诱导的结肠炎恶化。HFrD 喂养通过减少结肠黏液的厚度和改变结肠黏液的质量，增强了肠腔微生物进入结肠黏膜的途径。喂养 HFrD 还改变了肠道微生物种群和代谢，包括减少保护性共生和胆汁盐水解酶表达微生物，以及增加管腔结合胆汁酸。对小鼠施用共轭胆汁酸会使 DSS 诱导的结肠炎恶化。HFrD 还使Il10 ^-/-小鼠和感染C.rodentium 的小鼠的结肠炎恶化。

结论

膳食果糖摄入过多具有促结肠炎作用，这可以通过常驻肠道微生物群的组成、分布和代谢功能的变化来解释。