Microbial -Enzymatic Mucin Metabolic Relay Suppresses Tumor Progression in Apcmin/+ mice

Compelling evidence established the gut microbiota as a pivotal regulator of colorectal cancer (CRC) progression, although stage-specific mechanisms remain unclear. Our investigation in Apcmin/+ mice mapped tumor growth and microbial shifts across early, intermediate, and advanced stages. In Apcmin/+ mice, tumor growth exhibited an initial rapid phase followed by a gradual deceleration. Our study elucidated a niche complementarity model of gut microbiota in suppressing CRC progression: both critical gut bacteria (Akkermansia muciniphila, Muribaculaceae and other taxa) and their enzymes (hexosaminidase and SusD) exhibited the relay pattern in metabolizing intestinal mucin and producing N-acetylglucosamine (GlcNAc). Furthermore, rectal administration of GlcNAc suppressed Wnt/β-catenin signaling activation, might potentially contributing to the deceleration of tumor growth in the mid-to-late stages of cancer. This interplay between gut bacteria may reflect the significance of functional redundancy in maintaining the stability of microbial function.