Cell:纵向多组学研究挖掘IBS发病机制
创作:mildbreeze 审核:mildbreeze 09月11日
  • 纳入51例IBS患者和24例健康人,分析6个月内多时间点的肠道菌群、代谢组、表观遗传组和转录组;
  • 便秘型患者中SCFA和初级胆汁酸(BA)减少,而腹泻型患者中色胺和初级BA增多,这些菌群代谢物参与刺激结肠液体分泌,其变化是造成IBS亚型症状的潜在原因;
  • 患者发病期间,菌群α多样性降低、β多样性升高,一种古菌增多,初级BA升高,但有个体差异;
  • 患者及其菌群的嘌呤降解增加,导致次黄嘌呤减少,结肠上皮的嘌呤缺乏可能参与了IBS病理。
主编推荐语
mildbreeze
肠道微生物组的变化可能参与了肠易激综合征(IBS)的发生发展,但背后的机制仍待深入挖掘。Cell最新发表了来自美国梅奥诊所Purna Kashyap团队与明尼苏达大学Dan Knights团队的研究,通过纵向取样的整合多组学方法,揭示了IBS及其不同亚型(便秘型、腹泻型)的肠道菌群组成和功能(代谢产物、基因)的变化特征,以及这些变化可能参与IBS发病的机制,相关的菌群代谢物和宿主-微生物代谢途径或是潜在的IBS治疗靶点。该研究是通过纵向多组学方法研究人类疾病机制的一个范例。
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Cell [IF:38.637]

Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome

纵向多组学揭示肠易激综合征背后的亚群特异性机制

10.1016/j.cell.2020.08.007

09-10, Article

Abstract & Authors:展开

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The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.

First Authors:
Ruben AT Mars,Yi Yang

Correspondence Authors:
Dan Knights,Purna C Kashyap

All Authors:
Ruben AT Mars,Yi Yang,Tonya Ward,Mo Houtti,Sambhawa Priya,Heather R Lekatz,Xiaojia Tang,Zhifu Sun,Krishna R Kalari,Tal Korem,Yogesh Bhattarai,Tenghao Zheng,Noam Bar,Gary Frost,Abigail J Johnson,Will van Treuren,Shuo Han,Tamas Ordog,Madhusudan Grover,Justin Sonnenburg,Mauro D'Amato,Michael Camilleri,Eran Elinav,Eran Segal,Ran Blekhman,Gianrico Farrugia,Jonathan R Swann,Dan Knights,Purna C Kashyap

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