Phylotype-level 16S rRNA analysis reveals new bacterial indicators of health state in acute murine colitis
Phylotype-level 16S rRNA analysis reveals new bacterial indicators of health state in acute murine colitis
复制标题
DOI：
10.1038/ismej.2012.39
复制
发表时间：
2012-11-01
期刊：
影响因子：
11
通讯作者：
Loy, Alexander
中科院分区：
文献类型：
--
作者：
Berry, David;Schwab, Clarissa;Loy, Alexander
人类炎症性肠病和小鼠实验性结肠炎模型与肠道微生物群组成的变化有关，但尚不清楚这种微生物群动态在什么分类/系统发育水平上可以指示健康或疾病。在这里，我们报告葡聚糖硫酸钠（DSS）诱导的结肠炎伴随着STAT 1（-/-）和野生型小鼠肠道微生物群的组成和功能的重大变化，如通过细菌16 S rRNA（基因）扩增子的454焦磷酸测序，元转录组学和定量荧光原位杂交所确定的。在DSS处理的小鼠中，细菌家族瘤胃球菌科、拟杆菌科、肠杆菌科、脱铁菌科和疣微菌科的相对丰度增加。比较16 S rRNA序列分析在最大可能的系统发育分辨率确定了几个指示剂DSS治疗，包括假定的粘蛋白降解剂阿克曼氏菌和粘螺菌。该分析还揭示了强烈对比的丰度变化之间的同科，特别是在毛螺菌。当读段在更高的分类学水平上分组时，这些广泛的微生物型水平的动态被隐藏。元转录组学分析提供了对小鼠肠道微生物群功能变化的见解，与调节和细胞信号传导、碳水化合物代谢和呼吸相关的基因转录增加，以及炎症期间鞭毛蛋白基因转录减少。这些发现（i）建立了DSS结肠炎模型中小鼠肠道微生物群及其元转录组的第一个深入清单，（ii）揭示了家族水平的微生物群落分析不足以揭示重要的结肠炎相关微生物群变化，以及（iii）支持DSS治疗小鼠中富含细菌型和遗传多样性的毛螺菌科家族内结构和功能发生变化的情况。The ISME Journal（2012）6，2091-2106; doi：10.1038/ismej.2012.39; 2012年5月10日在线发表
Human inflammatory bowel disease and experimental colitis models in mice are associated with shifts in intestinal microbiota composition, but it is unclear at what taxonomic/phylogenetic level such microbiota dynamics can be indicative for health or disease. Here, we report that dextran sodium sulfate (DSS)-induced colitis is accompanied by major shifts in the composition and function of the intestinal microbiota of STAT1(-/-) and wild-type mice, as determined by 454 pyrosequencing of bacterial 16S rRNA (gene) amplicons, metatranscriptomics and quantitative fluorescence in situ hybridization of selected phylotypes. The bacterial families Ruminococcaceae, Bacteroidaceae, Enterobacteriaceae, Deferribacteraceae and Verrucomicrobiaceae increased in relative abundance in DSS-treated mice. Comparative 16S rRNA sequence analysis at maximum possible phylogenetic resolution identified several indicator phylotypes for DSS treatment, including the putative mucin degraders Akkermansia and Mucispirillum. The analysis additionally revealed strongly contrasting abundance changes among phylotypes of the same family, particularly within the Lachnospiraceae. These extensive phylotype-level dynamics were hidden when reads were grouped at higher taxonomic levels. Metatranscriptomic analysis provided insights into functional shifts in the murine intestinal microbiota, with increased transcription of genes associated with regulation and cell signaling, carbohydrate metabolism and respiration and decreased transcription of flagellin genes during inflammation. These findings (i) establish the first in-depth inventory of the mouse gut microbiota and its metatranscriptome in the DSS colitis model, (ii) reveal that family-level microbial community analyses are insufficient to reveal important colitis-associated microbiota shifts and (iii) support a scenario of shifting intra-family structure and function in the phylotype-rich and phylogenetically diverse Lachnospiraceae in DSS-treated mice. The ISME Journal (2012) 6, 2091-2106; doi:10.1038/ismej.2012.39; published online 10 May 2012