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Galactooligosaccharide supplementation provides protection against Citrobacter rodentium-induced colitis without limiting pathogen burden

机译:低聚半乳糖补充剂可预防啮齿类柠檬酸杆菌引起的结肠炎而不会限制病原体负担

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摘要

Many enteric pathogens, including Salmonella and enteropathogenic and enterohemorrhagic Escherichia coli, express adhesins that recognize and bind to carbohydrate moieties expressed on epithelial cells. An attractive strategy for inhibiting bacterial adherence employs molecules that mimic these epithelial binding sites. Prebiotic oligosaccharides are non-digestible, fermentable fibres capable of modulating the gut microbiota. Moreover, they may act as molecular decoys that competitively inhibit adherence of pathogens to host cells. In particular, galactooligosaccharides (GOS) and other prebiotic fibres have been shown to inhibit pathogen adherence to epithelial cells in vitro. In the present study, we determined the ability of prophylactic GOS administration to reduce enteric pathogen adherence both in vitro and in vivo as well as protect against intestinal inflammation. GOS supplementation significantly reduced the adherence of the epithelial-adherent murine bacterial pathogen Citrobacter rodentium in a dose-dependent manner to the surface of epithelial cells in vitro. A 1- to 2-log reduction in bacterial adherence was observed at the lowest and highest doses tested, respectively. However, mouse studies revealed that treatment with GOS neither reduced the adherence of C. rodentium to the distal colon nor decreased its dissemination to systemic organs. Despite the absence of adherence inhibition, colonic disease scores for GOS-treated, C. rodentium-infected mice were significantly lower than those of untreated C. rodentium-infected animals (P=0.028). Together, these data suggest that GOS has a direct protective effect in ameliorating disease severity following C. rodentium infection through an anti-adherence-independent mechanism.
机译:许多肠胃病原体,包括沙门氏菌,肠致病性肠出血性和肠出血性大肠杆菌,表达的粘附素识别并结合上皮细胞表达的碳水化合物部分。抑制细菌粘附的有吸引力的策略是采用模拟这些上皮结合位点的分子。益生元低聚糖是不易消化的,可发酵的纤维,能够调节肠道菌群。此外,它们可以作为分子诱饵,竞争性地抑制病原体与宿主细胞的粘附。特别地,低聚半乳糖(GOS)和其他益生元纤维已显示出在体外抑制病原体粘附于上皮细胞的能力。在本研究中,我们确定了预防性GO​​S施用在体外和体内减少肠道病原体依从性以及预防肠道炎症的能力。在体外,GOS的补充显着降低了上皮粘附的鼠类细菌病原体啮齿类柠檬酸杆菌对剂量的依赖性。在测试的最低和最高剂量下,细菌附着力分别下降了1至2个对数。但是,小鼠研究表明,GOS处理既不会降低啮齿类梭菌对远端结肠的粘附,也不会降低其向全身器官的扩散。尽管没有粘附抑制作用,但经GOS处理的感染了C. rodentium的小鼠的结肠疾病评分显着低于未处理的感染了C. rodentium的动物(P = 0.028)。总之,这些数据表明,GOS通过独立于抗粘附的机制,在改善啮齿类念珠菌感染后的疾病严重程度方面具有直接的保护作用。

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