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Oral Candida administration in a Clostridium difficile mouse model worsens disease severity but is attenuated by Bifidobacterium
PLOS ONE ( IF 3.7 ) Pub Date : 2019-01-15 , DOI: 10.1371/journal.pone.0210798
Wimonrat Panpetch , Naraporn Somboonna , Matanee Palasuk , Pratsanee Hiengrach , Malcolm Finkelman , Somying Tumwasorn , Asada Leelahavanichkul

Gut fungi may influence the course of Clostridium difficile infection either positively or negatively for the host. Fungi are not prominent in the mouse gut, and C. albicans, the major human gastrointestinal commensal yeast, is in low abundance or absent in mice. Bifidobacterium is one of the probiotics that may attenuate the severity of C. difficile infection. Inflammatory synergy between C. albicans and C. difficile, in gut, may provide a state that more closely resembles human infection and be more suitable for testing probiotic effects. We performed fecal mycobiota analysis and administered C. albicans at 1 day prior to C. difficile dosing. Fecal eukaryotic 18S rDNA analysis demonstrated the presence of Ascomycota, specifically, Candida spp., after oral antibiotics, despite negative fecal fungal culture. C. albicans administration enhanced the severity of the C. difficile infection model as determined by mortality rate, weight loss, gut leakage (FITC-dextran assay), and serum and intestinal tissue cytokines. This occurred without increased fecal C. difficile or bacteremia, in comparison with C. difficile gavage alone. Candida lysate with C. difficile increased IL-8 production from HT-29 and Caco-2 human intestinal epithelial cell-lines. Bifidobacterium attenuated the disease severity of the C. difficile plus Candida model. The reduced severity was associated with decreased Candida burdens in feces. In conclusion, gut C. albicans worsened C. difficile infection, possibly through exacerbation of inflammation. Hence, a mouse model of Clostridium difficile infection with C. albicans present in the gut may better model the human patient condition. Gut fungal mycobiome investigation in patients with C. difficile is warranted and may suggest therapeutic targets.



中文翻译:

艰难梭菌小鼠模型中口服念珠菌会使病情恶化,但会被双歧杆菌减弱

肠道真菌可能对宿主的艰难梭菌感染过程产生正向或负向影响。真菌在小鼠肠道和C中并不突出。白色念珠菌(主要的人类胃肠共生酵母)含量低或在小鼠中不存在。双歧杆菌是可减轻C严重程度的益生菌之一。感染。C.之间的炎症协同作用。白色念珠菌Ç艰难的肠道中的,可能会提供一种更类似于人类感染的状态,并且更适合测试益生菌的作用。我们进行粪便mycobiota分析和管理ÇC之前1天的白色念珠菌加药。粪便真核生物18S rDNA分析表明,尽管粪便真菌培养阴性,口服抗生素后仍存在子囊菌,特别是念珠菌Ç。施用白色念珠菌会加剧C的严重性。艰难的由死亡率,体重减轻,肠漏(FITC-葡聚糖测定)以及血清和肠组织细胞因子确定的感染模型。这没有发生粪便增加Ç艰难梭菌或菌血症,与C相比。仅管管饲。念珠菌C裂解液。艰难梭菌增加了HT-29和Caco-2人肠上皮细胞系的IL-8产量。双歧杆菌减毒的疾病的严重程度Ç艰难念珠菌模型。严重程度降低与念珠菌减少有关粪便的负担。总之,肠道Ç白色念珠使C恶化。难于感染,可能是由于炎症加重。因此,小鼠模型艰难梭菌感染Ç。肠道中存在的白色念珠菌可以更好地模拟人类患者的状况。肠道患者真菌mycobiome调查Ç艰难梭菌是有必要的,并可能提示治疗靶点。

更新日期:2019-01-16
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