Mice model Raw sequence reads

Background: 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. Until recently, much attention has been given to the role of mucosal response to DSS treatment, and only few studies investigated colonic microbiota in relation to DSS. We investigated compositional and functional changes of the microbiomes of the colon tissue and feces in mice treated with DSS. Methods: 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 was subjected to MiSeq Illumina sequencing. Alpha- and beta-diversities, and differences at the phylum and genus levels were determined, and bacterial functional pathways were predicted. Results: DSS increased disease severity, serum CRP and cytokines IL-1ß and IL-6, but decreased bacterial species richness, and shifted bacterial community composition only in the fecal samples. Bacteroides ovatus, Turicibacter, Escherichia, Clostridium, rc4-4, Enterobacteriaceae, Clostridiaceae, Bacteroidaceae, RF39, RF32, and Bacteroidales taxa were associated with DSS treatment. Also, DSS altered microbial functional pathways in both colonic mucosa and fecal samples. Conclusions: The development of colitis in DSS model was accompanied with the disruption of gut microbiota. While colitis development is driven by an interplay between mucosal epithelial damage, an inflammatory response, and a dysbiotic microbiota, it is however, not clear if DSS directly induces dysbiosis, or if microbiota dysbiosis occurs as a result of mucosal damage and inflammatory response.

背景：目前应用最广泛、特征研究最为充分的溃疡性结肠炎（UC, ulcerative colitis）实验模型为上皮损伤型硫酸葡聚糖硫酸钠（DSS, dextran sulfate sodium）诱导性结肠炎，该模型通过在饮用水中给予DSS构建。直至近期，多数研究聚焦于黏膜应答在DSS处理中的作用，仅有少数探讨了结肠微生物群与DSS的关联。本研究针对经DSS处理的小鼠，探究其结肠组织与粪便微生物组的组成及功能变化。
方法：将C57Bl/6小鼠置于含5% DSS的饮用水中连续饲养5天。通过临床评估、结肠组织细胞因子水平检测及血清C反应蛋白（C-reactive protein, CRP）检测，对炎症程度进行评价。采集结肠黏膜与粪便样本以提取DNA，对细菌16S rRNA的V4可变区进行Illumina MiSeq测序。测定α多样性与β多样性，分析菌群在门及属水平的组成差异，并预测细菌功能通路。
结果：DSS处理可升高疾病严重程度、血清CRP及白细胞介素1β（interleukin 1β, IL-1β）、白细胞介素6（interleukin 6, IL-6）水平，但降低细菌物种丰富度，且仅在粪便样本中引起细菌群落组成偏移。卵形拟杆菌（Bacteroides ovatus）、Turicibacter、埃希氏菌属（Escherichia）、梭菌属（Clostridium）、rc4-4、肠杆菌科（Enterobacteriaceae）、梭菌科（Clostridiaceae）、拟杆菌科（Bacteroidaceae）、RF39、RF32及拟杆菌目（Bacteroidales）类群与DSS处理存在显著关联。此外，DSS还可改变结肠黏膜与粪便样本中的微生物功能通路。
结论：DSS诱导的结肠炎模型中，肠道微生物群稳态遭到破坏。尽管结肠炎的发生由黏膜上皮损伤、炎症应答与菌群失调之间的相互作用所介导，但目前仍不清楚DSS是直接诱导菌群失调，还是菌群失调继发于黏膜损伤与炎症应答。