Multi-omics Analysis Reveals How Intratumoral Bacteria Shape the Immune Microenvironment in Gastric Cancer.

Area of Science:

• Microbiology
• Oncology
• Immunology

Background:

• Gastric cancer (GC) development is linked to gastric microbiota dysbiosis and altered host microenvironments.
• The intricate interplay between intratumoral bacteria and the gastric microenvironment is not fully understood.

Purpose of the Study:

• To comprehensively characterize the biological profiles of intratumoral bacteria, metabolome, and proteome in gastric cancer.
• To identify potential biomarkers for early gastric cancer detection through the analysis of host-microbe interactions.

Main Methods:

• Analysis of intratumoral bacteria, metabolome, and proteome in 20 GC tumors and paired non-tumor tissues.
• Integration of six independent datasets (497 gastric tissue biopsies, 554 normal tissues) and mucosal tissues from 10 healthy individuals.
• Comparative analysis of microbial diversity, species enrichment, and differentially expressed immune-related proteins.

Main Results:

• Gastric tumor tissues exhibited significantly higher microbial diversity and richness compared to non-tumor tissues.
• Specific bacteria, including Bacteroides thetaiotaomicron and Lactobacillus parabrevis, were enriched in tumors.
• 39 human immunity-related proteins, particularly in the tryptophan metabolic pathway, were differentially expressed, with certain pathways showing potential as early GC biomarkers.

Conclusions:

• The study provides a detailed framework for understanding the complex interactions between the tumor immune microenvironment and intratumoral bacteria in gastric cancer.
• Identified microbial and host protein signatures offer promising avenues for the early diagnosis of gastric cancer.
• Alterations in microbial composition and host immune pathways are critical features of the gastric tumor microenvironment.