• 分析炎症性肠病(IBD)和对照个体的粪便样本(2个队列共220例),代谢组谱和宏基因组谱与肠道炎症标志物粪便钙网蛋白有广泛关联;
  • 鉴定出>2700个在IBD中丰度改变的代谢物,鞘脂类和胆汁酸富集,三酰基甘油和四吡咯减少,还有>50%的未知代谢物,有些可能源于菌群;
  • 肠道菌群组成及其功能的变化,反映出对IBD肠道氧化应激的适应;
  • 鉴定出122个与IBD相关的菌群物种与代谢物的关联;
  • 可基于代谢组和宏基因组数据对IBD状态和亚型进行预测。
炎症性肠病(IBD)相关的肠道菌群研究,今年取得了不少进展。美国Broad Institute的牛人Ramnik J. Xavier团队,本周在Nature Microbiology发表了最新研究,用非靶向代谢组学和宏基因组学方法,分析了克罗恩病和溃疡性结肠炎患者以及非IBD个体的粪便样本,鉴定出与IBD相关的代谢物、菌群物种和酶,以及彼此间的关联,建立了基于代谢组和宏基因组的预测模型,并且这些发现在另一个独立队列样本中也大多得到验证,为深入研究IBD中菌群与代谢物的关联和机制打下基础,也提供了不少潜在的IBD诊断标志物和治疗靶点。

Gut microbiome structure and metabolic activity in inflammatory bowel disease



2018-12-10, Article

Abstract & Authors:展开

The inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome—the molecular interface between host and microbiota—are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic ‘guilt by association’ (covariation with known metabolites). Differentially abundant species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between differentially abundant species and well-characterized differentially abundant metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome–metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets.

First Authors:
Eric A Franzosa,Alexandra Sirota-Madi

Correspondence Authors:
Curtis Huttenhower,Ramnik J Xavier

All Authors:
Eric A Franzosa,Alexandra Sirota-Madi,Julian Avila-Pacheco,Nadine Fornelos,Henry J Haiser,Stefan Reinker,Tommi Vatanen,A Brantley Hall,Himel Mallick,Lauren J McIver,Jenny S Sauk,Robin G Wilson,Betsy W Stevens,Justin M Scott,Kerry Pierce,Amy A Deik,Kevin Bullock,Floris Imhann,Jeffrey A Porter,Alexandra Zhernakova,Jingyuan Fu,Rinse K Weersma,Cisca Wijmenga,Clary B Clish,Hera Vlamakis,Curtis Huttenhower,Ramnik J Xavier