基于16S rRNA高通量测序技术分析小鼠实验性结肠炎肠道菌群结构特征

Analysis of structural characteristics of gut microbiome in colitis mice based on 16S rRNA high-throughput sequencing

目的:明确溃疡性结肠炎(ulcerative colitis,UC)与肠道菌群间的相互关系,为寻找简单、安全的UC治疗方法提供实验基础。方法:通过3%硫酸葡聚糖钠(dextran sulfate sodium,DSS)诱导建立小鼠溃疡性结肠炎模型,观察检测体重变化、肠道病理改变,采用16S rRNA高通量测序技术,检测小鼠粪便中的肠道菌群,并分析比较结肠炎小鼠与正常小鼠间肠道菌群的多样性及丰度。同时,利用已有数据库,预估肠道菌群内的功能基因构成,分析2组间的菌群基因功能差异。结果:溃疡性结肠炎小鼠体重明显减轻,且肠道上皮完整性被破坏,同时肠道菌群多样性明显降低,溃疡性肠炎组小鼠肠道内双歧杆菌属降至0.2%明显低于正常组小鼠(P<0.05),而乳酸杆菌属平均丰度也显著降低至2.9%(P<0.05),提示可能是通过影响机体代谢从而造成溃疡性结肠炎的发生、发展。结论:溃疡性结肠炎小鼠的肠道菌群多样性降低,菌群分布均发生显著改变。

Objective: To clarify the interrelationship between ulcerative colitis(UC) and gut microbiome for providing an experimental basis to find a simple and safe treatment for patients with ulcerative colitis. Methods: A model of ulcerative colitis in mice was established by 3% DSS(dextran sulfate sodium), and the body weight and intestinal pathological changes of the model mice were detected. The diversity and differences of gut microbiome in feces of ulcerative colitis mice and normal mice were identified by 16 S rRNA high-throughput sequencing technology. The existing gene database was used to estimate the functional gene composition of the intestinal flora and the functional differences between the two groups. Results: The results of comparative analysis showed that the weight of ulcerative colitis mice was significantly reduced, the integrity of intestinal epithelium was destroyed, and the diversity of gut microbiome was significantly reduced. Bifidobacterium in intestinal tract of ulcerative colitis mice decreased to 0.2%, which was significantly lower than that of mice in control group(P<0.05);and the relative abundance of Lactobacillus also decreased to 2.9%(P<0.05), which denoted that ulcerative colitis might be caused by its influence on metabolism of the body. Conclusions: The diversity and distribution of gut microbiome in ulcerative colitis mice have changed significantly.