Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development.

Area of Science:

• Gastroenterology
• Microbiome Research
• Cancer Biology

Background:

• Colorectal cancer (CRC) incidence and mortality are higher in men than women.
• The underlying reasons for this sexual dimorphism in CRC remain incompletely understood.

Purpose of the Study:

• To investigate the role of sex-biased gut microbiota and metabolites in colorectal cancer (CRC) sexual dimorphism.
• To elucidate the mechanisms contributing to increased CRC risk and severity in males.

Main Methods:

• Utilized ApcMin/+ and azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse models to study colorectal tumorigenesis.
• Employed pseudo-germ mice colonized with fecal samples from male or female donors (mice or patients) to assess gut barrier function and inflammation.
• Analyzed gut microbiota composition and identified key metabolites involved in sex-biased tumorigenesis.

Main Results:

• Male mice exhibited significantly larger and more numerous colorectal tumors, alongside impaired gut barrier function.
• Pseudo-germ mice receiving male fecal samples showed exacerbated intestinal damage and inflammation.
• Identified an increase in Akkermansia muciniphila and a decrease in Parabacteroides goldsteinii in males, with sex-biased metabolites impacting glycerophospholipid metabolism.

Conclusions:

• Sex-biased gut microbiome and metabolites are key contributors to sexual dimorphism in colorectal cancer (CRC).
• Targeting these sex-biased microbial and metabolic alterations presents a potential therapeutic strategy for CRC, tailored to sex-specific differences.