A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis
Abstract 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 infl...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2021-01-01
|
Series: | Microbiome |
Subjects: | |
Online Access: | https://doi.org/10.1186/s40168-020-00967-x |
id |
doaj-1c8befc284dd456ab6ba9100530c20e7 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhixiang Yan Feixiang He Fei Xiao Huanhuan He Dan Li Li Cong Lu Lin Huijin Zhu Yanyan Wu Ru Yan Xiaofeng Li Hong Shan |
spellingShingle |
Zhixiang Yan Feixiang He Fei Xiao Huanhuan He Dan Li Li Cong Lu Lin Huijin Zhu Yanyan Wu Ru Yan Xiaofeng Li Hong Shan A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis Microbiome Metaproteomics Gut microbial proteolysis Inflammatory bowel disease |
author_facet |
Zhixiang Yan Feixiang He Fei Xiao Huanhuan He Dan Li Li Cong Lu Lin Huijin Zhu Yanyan Wu Ru Yan Xiaofeng Li Hong Shan |
author_sort |
Zhixiang Yan |
title |
A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis |
title_short |
A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis |
title_full |
A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis |
title_fullStr |
A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis |
title_full_unstemmed |
A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis |
title_sort |
semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis |
publisher |
BMC |
series |
Microbiome |
issn |
2049-2618 |
publishDate |
2021-01-01 |
description |
Abstract 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. Video abstract |
topic |
Metaproteomics Gut microbial proteolysis Inflammatory bowel disease |
url |
https://doi.org/10.1186/s40168-020-00967-x |
work_keys_str_mv |
AT zhixiangyan asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT feixianghe asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT feixiao asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT huanhuanhe asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT danli asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT licong asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT lulin asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT huijinzhu asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT yanyanwu asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT ruyan asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT xiaofengli asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT hongshan asemitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT zhixiangyan semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT feixianghe semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT feixiao semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT huanhuanhe semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT danli semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT licong semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT lulin semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT huijinzhu semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT yanyanwu semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT ruyan semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT xiaofengli semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis AT hongshan semitrypticpeptidecentricmetaproteomicminingapproachanditspotentialutilityincapturingsignaturesofgutmicrobialproteolysis |
_version_ |
1724334120207646720 |
spelling |
doaj-1c8befc284dd456ab6ba9100530c20e72021-01-17T12:55:10ZengBMCMicrobiome2049-26182021-01-019111910.1186/s40168-020-00967-xA semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysisZhixiang Yan0Feixiang He1Fei Xiao2Huanhuan He3Dan Li4Li Cong5Lu Lin6Huijin Zhu7Yanyan Wu8Ru Yan9Xiaofeng Li10Hong Shan11Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Endocrinology and Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Gastroenterology, The Fifth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Gastroenterology, The Fifth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen UniversityState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauDepartment of Gastroenterology, The Fifth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen UniversityAbstract 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. Video abstracthttps://doi.org/10.1186/s40168-020-00967-xMetaproteomicsGut microbial proteolysisInflammatory bowel disease |