Acute dextran sulfate sodium (DSS)-induced colitis promotes gut microbial dysbiosis in mice

Acute dextran sulfate sodium (DSS)-induced colitis promotes gut microbial dysbiosis in mice
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DOI:
10.1002/jobm.201500726
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发表时间:
2016-09-01
影响因子:
3.1
通讯作者:
Ghia, Jean-Eric
Ghia, Jean-Eric
中科院分区:
生物学4区
文献类型:
--
作者:
Munyaka, Peris Mumbi;Rabbi, Mohammad Fazle;Ghia, Jean-Eric

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溃疡性结肠炎(UC)最广泛使用和表征的实验模型是上皮糜烂、葡聚糖硫酸钠(DSS)诱导的结肠炎,其通过在饮用水中施用DSS而开发。我们研究了粪便和结肠粘膜的微生物组成和功能的变化与DSS治疗的小鼠。C57 B1/6小鼠接受在饮用水中的5%DSS 5天。通过临床和结肠组织细胞因子水平和血清中C反应蛋白(CRP)的分析来评估炎症。使用结肠粘膜和粪便样品进行DNA提取,并对细菌16 S rRNA基因的V4区进行MiSeq Illumina测序。α-和β-二聚体,并在门和属水平的组成差异进行了测定,和细菌的功能途径进行了预测。DSS增加了疾病的严重程度,血清CRP和细胞因子IL-1和IL-6,但减少了细菌物种丰富度,并改变了细菌群落组成。拟杆菌属、Turicibacter、埃希氏菌属、梭菌属、肠杆菌科、梭菌科、拟杆菌科、拟杆菌目以及其他分类群与粪便和结肠样品中的DSS处理相关。此外,DSS改变了结肠粘膜和粪便样品中的微生物功能途径。结论:DSS模型中结肠炎的发展伴随着微生物多样性的减少和肠道微生物群在较低分类水平上的生态失调。
The most widely used and characterized experimental model of ulcerative colitis (UC) is the epithelial erosion, dextran sulfate sodium (DSS)-induced colitis, which is developed by administration of DSS in drinking water. We investigated fecal and colonic mucosa microbial composition and functional changes in mice treated with DSS. C57Bl/6 mice received 5% DSS in drinking water for 5 days. Inflammation was evaluated clinically and by analysis of colonic tissue cytokine levels and C-reactive protein (CRP) in the serum. Colonic mucosa and fecal samples were used for DNA extraction and the V4 region of bacterial 16S rRNA gene was subjected to MiSeq Illumina sequencing. Alpha- and beta-diversities, and compositional differences at phylum and genus levels were determined, and bacterial functional pathways were predicted. DSS increased disease severity, serum CRP and cytokines IL-1 and IL-6, but decreased bacterial species richness, and shifted bacterial community composition. Bacteroides, Turicibacter, Escherichia, Clostridium, Enterobacteriaceae, Clostridiaceae, Bacteroidaceae, Bacteroidales, among other taxa were associated with DSS treatment in fecal and colonic samples. Also, DSS altered microbial functional pathways in both colonic mucosa and fecal samples. Conclusions: The development of colitis in DSS model was accompanied with reduced microbial diversity and dysbiosis of gut microbiota at lower taxonomical levels.