Influence of transgenic MUC13 expression on gut microbiota and chemokine profile

Background: MUC13 is an important oncoprotein that is often overexpressed in cancers, including colorectal cancer, and is linked to worse outcomes, although its exact role is not fully understood. Using a MUC13 transgenic mouse model, we examined how MUC13 overexpression affects gut microbiome and cytokines that can influence cancer risk and treatment responses. Methods: Fecal specimens were collected from MUC13-overexpressing transgenic mice (MUC13Tg) and wild-type mice. To assess the fecal bacterial communities, we performed DNA extraction followed by 16S rRNA metagenomic sequencing on the Illumina MiSeq platform. Additionally, colon tissues from MUC13Tg and wild-type mice were assessed by IHC to confirm the overexpression of MUC13. Furthermore, chemokine profiling analyses were performed using chemokines arrays in serum samples of MUC13-overexpressing mice and wild-type mice, respectively. Results: IHC confirmed elevated MUC13 expression in the colon of transgenic mice, leading us to investigate associated changes in the gut and immune environment. 16S rRNA sequencing showed clear shifts in the gut microbiota, with increases in Alistipes, Clostridium_XIVa, Oscillibacter, and TM7 (25→35%, 1.6→11.6%, 8.3→16.6%, 2.5→6.6%) and decreases in Parabacteroides and Akkermansia (31.6→11.6%, 15→3.3%) compared with wild-type mice. These microbial alterations were accompanied by cytokine changes, including elevated EGF, FGF21, CD93, and Leptin, as well as reduced levels of cytokines such as Angiopoietin-1, CD14, HGF, and CCL17. Together, these results demonstrate that MUC13 overexpression not only shifts gut microbial composition but also modifies systemic inflammatory signaling. Conclusion: This study suggests that MUC13 overexpression markedly alters the gut microbiome and cytokine expression profile in mice. The increased Firmicutes/Bacteroidetes ratio, enrichment of pro-inflammatory species, and repression of beneficial bacteria collectively indicate a shift toward gut dysbiosis and a pro-tumorigenic environment. These findings suggest that MUC13 plays a key role in shaping the gut microbial landscape and influencing immune modulation, both of which are important drivers of cancer development.