Microbiome:严志祥等深挖IBD肠道菌群蛋白酶解特征
创作:mildbreeze 审核:mildbreeze 01月26日
  • 开发以半胰蛋白酶解肽为核心的宏蛋白质组挖掘方法,分析IBD和健康人的623个宏蛋白质组数据,揭示出肠道微生物蛋白酶解特征在IBD中的变化;
  • IBD菌群功能变化主要涉及碳水化合物运输和代谢、氧化应激、细胞运动、蛋白质合成和成熟;
  • IBD菌群蛋白酶解特征的改变主要发生在回肠末端(克罗恩病)和降结肠(溃结);
  • 菌群蛋白酶解模式与β多样性低度相关、与微生物的蛋白酶和分子伴侣有一定关联、与宿主蛋白酶抑制剂和免疫球蛋白负相关。
主编推荐语
mildbreeze
蛋白酶解调控能通过快速降解错误折叠蛋白和激活调节蛋白,使得肠道微生物快速响应肠道环境的动态变化。在常规的宏蛋白质组学数据分析中通常不会纳入半胰蛋白酶解肽,然而这些肽主要源于内源性的蛋白酶解作用,可以为研究肠道菌群的特征和变化提供一个独到的视角。中山大学附属第五医院严志祥、单鸿、李啸峰和澳门大学燕茹与研究团队,近期在Microbiome发表文章,报道了一种以半胰蛋白酶解肽为核心的宏蛋白质组挖掘方法,采用综合的宏数据库、两步多引擎数据库搜索和高分辨率质谱数据集,可以分析人肠道菌群的蛋白酶解特征。该研究以炎症性肠病(IBD)为例,首次从公共数据集中发掘肠道菌群的蛋白酶解特征,在微生物种类和蛋白质丰度之外提供了IBD菌群变化的另一个层面的信息。该方法可用于研究宿主-菌群互作的调控,推荐专业人士参考。
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Microbiome [IF:14.65]

A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis

半胰蛋白酶解肽为核心的宏蛋白质组学挖掘方法及其在捕获肠道微生物蛋白酶解特征方面的潜在用途

10.1186/s40168-020-00967-x

01-12, Article

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Background: Proteolysis regulation allows gut microbes to respond rapidly to dynamic intestinal environments by fast degradation of misfolded proteins and activation of regulatory proteins. However, alterations of gut microbial proteolytic signatures under complex disease status such as inflammatory bowel disease (IBD, including Crohn’s disease (CD) and ulcerative colitis (UC)), have not been investigated. Metaproteomics holds the potential to investigate gut microbial proteolysis because semi-tryptic peptides mainly derive from endogenous proteolysis.
Results: We have developed a semi-tryptic peptide centric metaproteomic mining approach to obtain a snapshot of human gut microbial proteolysis signatures. This approach employed a comprehensive meta-database, two-step multiengine database search, and datasets with high-resolution fragmentation spectra to increase the confidence of semi-tryptic peptide identification. The approach was validated by discovering altered proteolysis signatures of Escherichia coli heat shock response. Utilizing two published large-scale metaproteomics datasets containing 623 metaproteomes from 447 fecal and 176 mucosal luminal interface (MLI) samples from IBD patients and healthy individuals, we obtain potential signatures of altered gut microbial proteolysis at taxonomic, functional, and cleavage site motif levels. The functional alterations mainly involved microbial carbohydrate transport and metabolism, oxidative stress, cell motility, protein synthesis, and maturation. Altered microbial proteolysis signatures of CD and UC mainly occurred in terminal ileum and descending colon, respectively. Microbial proteolysis patterns exhibited low correlations with β-diversity and moderate correlations with microbial protease and chaperones levels, respectively. Human protease inhibitors and immunoglobulins were mainly negatively associated with microbial proteolysis patterns, probably because of the inhibitory effects of these host factors on gut microbial proteolysis events.
Conclusions: This semi-tryptic peptide centric mining strategy offers a label-free approach to discover signatures of in vivo gut microbial proteolysis events if experimental conditions are well controlled. It can also capture in vitro proteolysis signatures to facilitate the evaluation and optimization of experimental conditions. Our findings highlight the complex and diverse proteolytic events of gut microbiome, providing a unique layer of information beyond taxonomic and proteomic abundance.

First Authors:
Zhixiang Yan

Correspondence Authors:
Zhixiang Yan,Ru Yan,Xiaofeng Li,Hong Shan

All Authors:
Zhixiang Yan,Feixiang He,Fei Xiao,Huanhuan He,Dan Li,Li Cong,Lu Lin,Huijin Zhu,Yanyan Wu,Ru Yan,Xiaofeng Li,Hong Shan

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