Decoding the human gut bacterial plasmids in colorectal cancer

Area of Science:

• Microbiome Research
• Genomics
• Colorectal Cancer (CRC) Pathogenesis

Background:

• Gut plasmids exhibit greater sensitivity to microenvironmental changes than their bacterial hosts.
• Understanding the role of plasmids in the gut microbiome is crucial for investigating diseases like colorectal cancer (CRC).

Purpose of the Study:

• To analyze the significance of gut plasmids in colorectal cancer (CRC) by characterizing plasmid and bacterial profiles, trace elements, and metabolites.
• To explore the impact of gut plasmids on bacterial functionality and map multi-omics interaction networks.

Main Methods:

• Metagenomic data analysis from 863 participants (CRC, high-risk, low-risk).
• Characterization of plasmid and bacterial profiles, trace elements, and metabolites.
• Functional gene assessment (antibiotic resistance genes [ARGs], mobile genetic elements [MGEs], metal resistance genes [MRGs], virulence factor genes [VFGs]), random forest modeling, and structural equation modeling (SEM).

Main Results:

• Plasmid abundance showed a decreasing trend in high-risk and CRC groups.
• Gut plasmids significantly influenced bacterial functional genes (ARGs, MGEs, MRGs, VFGs).
• A plasmid-based model demonstrated effective prediction of CRC risk.
• SEM identified key host bacteria (e.g., Enterobacterales, Campylobacterales) and plasmid markers, revealing complex interactions with trace elements and metabolites.

Conclusions:

• Gut plasmids play a significant role in CRC pathogenesis and can serve as predictive biomarkers.
• The study characterized gut plasmid composition and host interactions, providing insights into multi-omics networks relevant to CRC.