Abstract

The human microbiota comprises trillions of microbes, and the relationship between cancer and microbiota is very complex. The impact of fecal microbiota alterations on colorectal cancer (CRC) pathogenesis is emerging. This study analyzed changes in the microbial composition in CRC subjects with both fecal microbiota and gut microbe-derived extracellular vesicles (EVs). From August 2017 to August 2018, 70 CRC patients and 158 control subjects were enrolled in the study. Metagenomic profiling of fecal microbiota and gut microbe-derived EVs in stool was performed using 16S ribosomal DNA sequencing. Relative abundance, evenness, and diversity in both the gut microbiota and gut microbe-derived EVs were analyzed. Additionally, microbial composition changes according to the stage and location of CRC were analyzed. Microbial composition was significantly changed in CRC subjects compared to control subjects, with evenness and diversity significantly lower in the fecal microbiota of CRC subjects. Gut microbe-derived EVs of stool demonstrated significant differences in the microbial composition, evenness, and diversity in CRC subjects compared to the control subjects. Additionally, microbial composition, evenness, and diversity significantly changed in late CRC subjects compared to early CRC subjects with both fecal microbiota and gut microbe-derived EVs. Alistipes-derived EVs could be novel biomarkers for diagnosing CRC and predicting CRC stages. Ruminococcus 2-derived EVs significantly decreased in distal CRC subjects than in proximal CRC subjects. Gut microbe-derived EVs in CRC had a distinct microbial composition compared to the controls. Profiling of microbe-derived EVs may offer a novel biomarker for detecting and predicting CRC prognosis.

Highlights

  • Colorectal cancer (CRC) has become a global health problem because of the increasing incidence of Colorectal Cancer (CRC) in young adults [1, 2]

  • CRC subjects showed a significant enrichment of Bacteroidetes phylum and depletion of Actinobacteria phylum (p < 0.001, Table 1)

  • Within Actinobacteria, relative depletion was prominent for the Bifidobacterium (Bifidobacterium genus) family in CRC subjects

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Summary

Introduction

Colorectal cancer (CRC) has become a global health problem because of the increasing incidence of CRC in young adults [1, 2]. Western dietary patterns and obesity have been strongly linked to CRC development [3, 4]. Various studies have suggested that the pathogenesis of CRC is influenced by genetic factors and by gut microbial composition altered due to ingested food or environmental factors. Gut microbiota induce oxidative stress and DNA damage in response to chronic inflammation, cell proliferation, and the production of metabolites such as butyrate [5]. Fusobacterium nucleatum is associated with CRC pathogenesis by expressing a bacterial cell surface adhesion component, which can bind to host E-cadherin [6, 7]. Enterotoxigenic Bacteroides fragilis is enriched in human CRC, resulting in cell morphology changes, E-cadherin cleavage stimulation, and colonic barrier function reduction [8]

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