Crohn's Disease-Associated Adherent-Invasive Escherichia coli Adhesion Is Enhanced by Exposure to the Ubiquitous Dietary Polysaccharide Maltodextrin

Crohn's disease (CD) is associated with intestinal dysbiosis evidenced by an altered microbiome forming thick biofilms on the epithelium. Additionally, adherent-invasive E. coli (AIEC) strains are frequently isolated from ileal lesions of CD patients indicating a potential role for these strains in disease pathogenesis. The composition and characteristics of the host microbiome are influenced by environmental factors, particularly diet. Polysaccharides added to food as emulsifiers, stabilizers or bulking agents have been linked to bacteria-associated intestinal disorders. The escalating consumption of polysaccharides in Western diets parallels an increased incidence of CD during the latter 20th century. In this study, the effect of a polysaccharide panel on adhesiveness of the CD-associated AIEC strain LF82 was analyzed to determine if these food additives promote disease-associated bacterial phenotypes. Maltodextrin (MDX), a polysaccharide derived from starch hydrolysis, markedly enhanced LF82 specific biofilm formation. Biofilm formation of multiple other E. coli strains was also promoted by MDX. MDX-induced E. coli biofilm formation was independent of polysaccharide chain length indicating a requirement for MDX metabolism. MDX exposure induced type I pili expression, which was required for MDX-enhanced biofilm formation. MDX also increased bacterial adhesion to human intestinal epithelial cell monolayers in a mechanism dependent on type 1 pili and independent of the cellular receptor CEACAM6, suggesting a novel mechanism of epithelial cell adhesion. Analysis of mucosa-associated bacteria from individuals with and without CD showed increased prevalence of malX, a gene essential for MDX metabolism, uniquely in the ileum of CD patients. These findings demonstrate that the ubiquitous dietary component MDX enhances E. coli adhesion and suggests a mechanism by which Western diets rich in specific polysaccharides may promote dysbiosis of gut microbes and contribute to disease susceptibility.克罗恩病（Crohn’s disease，CD）与肠道菌群失调密切相关，该失调的特征为微生物组发生改变，且在上皮表面形成厚层生物膜。此外，从克罗恩病患者的回肠病变组织中常分离得到黏附侵袭性大肠杆菌（adherent-invasive E. coli，AIEC）菌株，提示此类菌株在疾病发病机制中可能具有潜在作用。宿主微生物组的组成与特征受环境因素影响，其中膳食的作用尤为显著。作为乳化剂、稳定剂或填充剂添加至食品中的多糖，已被证实与细菌相关性肠道疾病存在关联。20世纪后期，西式膳食中多糖的消费量持续攀升，与此同时CD的发病率也逐渐升高。本研究分析了一组多糖对CD相关AIEC菌株LF82黏附特性的影响，以明确此类食品添加剂是否会促进疾病相关的细菌表型。麦芽糊精（maltodextrin，MDX）是一种经淀粉水解得到的多糖，可显著增强LF82的特异性生物膜形成能力。MDX同样可促进多种其他大肠杆菌菌株的生物膜形成。MDX诱导的大肠杆菌生物膜形成与多糖链长无关，提示该过程依赖于MDX的代谢。MDX暴露可诱导I型菌毛的表达，而I型菌毛是MDX增强生物膜形成所必需的。此外，MDX可通过依赖I型菌毛但不依赖细胞受体CEACAM6的机制，增强细菌对人肠上皮细胞单层的黏附能力，这提示了一种全新的上皮细胞黏附机制。对伴或不伴CD的个体黏膜相关细菌的分析显示，MDX代谢必需基因malX的携带率仅在CD患者的回肠组织中显著升高。本研究结果表明，作为普遍存在的膳食成分的MDX可增强大肠杆菌的黏附能力，并提示富含特定多糖的西式膳食可能通过此种机制促进肠道微生物群失调，进而增加疾病易感性。