He Qing, Li Xiaoping, Liu Chuan, Su Lili, Xia Zhongkui, Li Xin, Li Ying, Li Lingling, Yan Ting, Feng Qiang, Xiao Liang
Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China.
BGI-Shenzhen, Shenzhen, 518083, China.
Appl Microbiol Biotechnol. 2016 May;100(10):4485-94. doi: 10.1007/s00253-015-7205-x. Epub 2016 Jan 21.
Crohn's disease (CD) is characterized by chronic transmural inflammation. The symptom of the mice model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) is closed to human under CD condition, so this kind of animal is widely used in the related researches. Although the dysbiosis of the fecal microbiota has been proved to play an important role in the patients with CD, the composition of the gastrointestinal microbiota in the mouse model under disease condition is still unclear. In the current study, male 7-week BALB/c mice were anesthetized and intrarectal administrated by ethanol (ET group), TNBS in ethanol (TN group), and phosphate buffered saline (PBS) (CK group) as control. The symptoms of individuals under the CD condition were observed, and the changes of the bacterial taxonomic structure and functional composition were revealed by next-generation sequencing (NGS) 16S sequencing. The BALB/c mice in TN group demonstrated CD-like symptoms and the damages in the intestinal tract. The NGS 16S results exhibited that the diversity and microbial composition under CD condition are significantly different with those in ET group. The KEGG Orthology (KO) profile were generated from PICRUSt, and function modules such as methanogenesis (M00347) and microcin C transport system (M00349) were found enriched in the individuals in the TN group. This study proved that mouse model induced by TNBS could develop the similar symptom to CD patient, and we firstly showed the significant intestinal microbe changes on both taxonomic structure and functional composition in this mouse model.
克罗恩病(CD)的特征是慢性透壁性炎症。2,4,6-三硝基苯磺酸(TNBS)诱导的小鼠模型的症状在CD条件下与人类相似,因此这种动物被广泛用于相关研究。尽管已证明粪便微生物群失调在CD患者中起重要作用,但疾病状态下小鼠模型中胃肠道微生物群的组成仍不清楚。在本研究中,将7周龄雄性BALB/c小鼠麻醉,分别经直肠给予乙醇(ET组)、乙醇中的TNBS(TN组)和磷酸盐缓冲盐水(PBS)(CK组)作为对照。观察CD条件下个体的症状,并通过下一代测序(NGS)16S测序揭示细菌分类结构和功能组成的变化。TN组的BALB/c小鼠表现出类似CD的症状和肠道损伤。NGS 16S结果显示,CD条件下的多样性和微生物组成与ET组有显著差异。从PICRUSt生成KEGG直系同源物(KO)图谱,发现TN组个体中富集了诸如产甲烷作用(M00347)和微菌素C转运系统(M00349)等功能模块。本研究证明TNBS诱导的小鼠模型可出现与CD患者相似的症状,并且我们首次展示了该小鼠模型在分类结构和功能组成方面肠道微生物的显著变化。