Metaproteomics characterizes human gut microbiome function in colorectal cancer

Shuping Long,Yi Yang,Yiwen Wang,Qin Qin,Liang Qiao,Anmei Deng,Chengpin Shen

doi:10.1038/s41522-020-0123-4

Abstract

Pathogenesis of colorectal cancer (CRC) is associated with alterations in gut microbiome. Previous studies have focused on the changes of taxonomic abundances by metagenomics. Variations of the function of intestinal bacteria in CRC patients compared to healthy crowds remain largely unknown. Here we collected fecal samples from CRC patients and healthy volunteers and characterized their microbiome using quantitative metaproteomic method. We have identified and quantified 91,902 peptides, 30,062 gut microbial protein groups, and 195 genera of microbes. Among the proteins, 341 were found significantly different in abundance between the CRC patients and the healthy volunteers. Microbial proteins related to iron intake/transport; oxidative stress; and DNA replication, recombination, and repair were significantly alternated in abundance as a result of high local concentration of iron and high oxidative stress in the large intestine of CRC patients. Our study shows that metaproteomics can provide functional information on intestinal microflora that is of great value for pathogenesis research, and can help guide clinical diagnosis in the future.

Highlights

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of oncological mortality worldwide[1]
After protein extraction and trypsin digestion, label-free data-independent acquisition (DIA) was used to identify and quantify proteins in each sample using a merged spectral library generated by datadependent acquisition (DDA) experiments performed on a pool from every sample and spectrum-centric analysis of the DIA data
The Human Microbiome Project (HMP) stool database was used for data analysis, in which the protein entries were translated from gut microbial genes confirmed in healthy crowds (80 males and 59 females)

Summary

Introduction

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of oncological mortality worldwide[1]. CRC incidence rates in developing countries have been rising because of obesity and westernized diet[2]. The pathogenesis of CRC is a complex multistep process involving genetic alterations[3], immune factors[4], environmental factors (e.g. diet and lifestyle)[5], and human gut microbiome[6]. Human gut hosts about 100 trillion microbes. Most microbes colonize the large intestine at a concentration of about 1012 cell per mL7. Emerging evidences indicate that microbial dysbiosis is a driving force in the pathogenesis of intestinal tumor[8]. Studies using metagenomics-based approaches demonstrated that Parvimonas micra, Solobacterium moorei, Fusobacterium nucleatum, and Peptostreptococcus stomatis are enriched in the gut of CRC patients[9].

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Results

Conclusion