(Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome-both models having been orally gavaged with Fn-jointly validated the causal role of Fn in impairing sIgA induction. We identified a dysregulated IgA maturation (IGAM) module in Fn-positive patients, indicating compromised mucosal immunity and increased bacterial infiltration. This IGAM signature effectively stratified Fn-positive patients, suggesting potential for targeted therapeutic approaches. Our findings reveal that Fn disrupts sIgA production, increasing tumor microbial burden and worsening prognosis through chronic inflammation in Fn-positive CRC.