Western Diet Promotes Intestinal Colonization by Collagenolytic Microbes and Promotes Tumor Formation After...

Area of Science:

• Gastroenterology
• Oncology
• Microbiology

Background:

• The Western diet, high in fat, is a modifiable risk factor for colorectal cancer recurrence post-surgery.
• Understanding the mechanisms linking diet, microbiome, and tumor recurrence is crucial for prevention strategies.

Purpose of the Study:

• To investigate how a Western diet influences tumor recurrence after colorectal resection in mice.
• To identify the role of the gut microbiome and bacterial enzymes in diet-induced tumor promotion.

Main Methods:

• Mice were fed either a standard or Western diet and underwent colorectal resection.
• Mice received antibiotics or a collagenase inhibitor (Pi-PEG) and were inoculated with tumor cells and collagenolytic bacteria (Enterococcus faecalis).
• Tumor formation, microbiome composition (16S rRNA sequencing), and bacterial distribution were analyzed.

Main Results:

• The Western diet significantly increased colorectal tumor formation (88% vs. 30%) compared to a standard diet.
• Tumorigenesis correlated with collagenolytic bacteria (Enterococcus faecalis, Proteus mirabilis).
• Antibiotics increased Candida parapsilosis, while Pi-PEG reduced tumor formation and maintained microbiome diversity.

Conclusions:

• Diet and antibiotic use can promote post-surgical colorectal tumorigenesis via specific microbial and enzymatic activities.
• Targeting microbial collagenase or preserving microbiome diversity may reduce colorectal cancer recurrence risk.