Commensal microbiota-derived metabolite agmatine triggers inflammation to promote colorectal tumorigenesis

Significant changes in gut bacteria were observed in a colorectal cancer mouse model.

• Gut microbial dysbiosis was monitored in a colorectal cancer mouse model without dietary or pharmacological intervention.
• Metabolomic profiling identified agmatine, a metabolite from gut bacteria, which may interact with Rnf128.
• Agmatine could suppress the ubiquitination of β-catenin, leading to the upregulation of downstream targets such as Cyclin D1, Lgr5, CD44, and C-myc.
• Activation of the Wnt signaling pathway is associated with dysplasia of intestinal cells and inflammatory infiltration of lymphocytes.
• This inflammatory response may involve increased levels of pro-inflammatory cytokines (IL-6 and TNF-α) and decreased levels of the anti-inflammatory cytokine (IL-10).
• The findings contribute to understanding the roles of gut microbiota in the development of colorectal cancer.

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