Clermont Université, 'Microbe intestin inflammation et Susceptibilité de l'Hôte', UMR1071 Inserm/Université d'Auvergne M2iSH, , Clermont-Ferrand, France.
Gut. 2014 Jan;63(1):116-24. doi: 10.1136/gutjnl-2012-304119. Epub 2013 Apr 18.
Western diet is a risk factor for Crohn's disease (CD). Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is abnormally expressed in CD patients. This allows adherent-invasive Escherichia coli (AIEC) to colonise the gut mucosa and leads to inflammation. We assessed the effects of a high fat/high sugar (HF/HS) Western diet on gut microbiota composition, barrier integrity and susceptibility to infection in transgenic CEABAC10 mice expressing human CEACAMs.
Colonic microbiota composition and susceptibility of CEABAC10 mice to AIEC LF82 bacteria infection were determined in mice fed a conventional or HF/HS diet. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein and mucin expression and localisation, and by determining histological score and levels of cytokine release.
HF/HS diet led to dysbiosis in WT and transgenic CEABAC10 mice, with a particular increase in E coli population in HF/HS-fed CEABAC10 mice. These mice showed decreased mucus layer thickness, increased intestinal permeability, induction of Nod2 and Tlr5 gene transcription, and increased TNFα secretion. These modifications led to a higher ability of AIEC bacteria to colonise the gut mucosa and to induce inflammation.
Western diet induces changes in gut microbiota composition, alters host homeostasis and promotes AIEC gut colonisation in genetically susceptible mice. These results support the multifactorial aetiology of CD and highlight the importance of diet in CD pathogenesis.
西式饮食是克罗恩病（CD）的一个风险因素。癌胚抗原相关细胞黏附分子 6（CEACAM6）在 CD 患者中异常表达。这使得黏附侵袭性大肠杆菌（AIEC）定植在肠道黏膜上，并导致炎症。我们评估了高脂肪/高糖（HF/HS）西式饮食对表达人类 CEACAMs 的转基因 CEABAC10 小鼠肠道微生物群落组成、屏障完整性和易感性感染的影响。
在给予常规或 HF/HS 饮食的 CEABAC10 小鼠中，确定了结肠微生物群落组成和 CEABAC10 小鼠对 AIEC LF82 细菌感染的易感性。通过研究肠道通透性、紧密连接蛋白和粘蛋白的表达和定位，以及确定组织学评分和细胞因子释放水平，评估了屏障功能和炎症反应。
HF/HS 饮食导致 WT 和转基因 CEABAC10 小鼠的菌群失调，HF/HS 喂养的 CEABAC10 小鼠中大肠杆菌种群尤其增加。这些小鼠表现出粘液层厚度变薄、肠道通透性增加、Nod2 和 Tlr5 基因转录诱导以及 TNFα 分泌增加。这些改变导致 AIEC 细菌更容易定植在肠道黏膜并引发炎症。
西式饮食引起肠道微生物群落组成的变化，改变宿主内环境平衡，并促进易感基因小鼠的 AIEC 肠道定植。这些结果支持 CD 的多因素病因，并强调了饮食在 CD 发病机制中的重要性。
