Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer
Colon cancer affects people of all ages. However, its frequency, as well as the related morbidity and mortality, are high among older adults. The complex physiological changes in the aging gut substantially limit the development of cancer therapies. Here, we identify a unique intestinal microenvironment that is linked with an increased risk of colon cancer in older adults. Our findings show that aging significantly influences persistent fucosylation of the apical surfaces of intestinal epithelial cells, which results in a favorable environment for tumor growth. Furthermore, our findings shed light on the significance of the host-commensal interaction in facilitating pathogenic fucosylation and tumor growth with age. We analyzed colonic microbial populations at the species level to find changes associated with aging that could contribute to the development of colon cancer. Analysis of single-cell RNA-seq (scRNAseq) data identifies distinct epithelial cell subtypes involved in dysregulated fucosylation in older adults. Overall, our study provides compelling evidence that excessive fucosylation is associated with the development of colon cancer, that age-related changes increase vulnerability to colon cancer, and that a decline in microbial diversity and metabolic changes in the homeostasis of older mice dysregulate fucosylation levels with age. It is interesting to know the potential impact of age-related dysbiosis on the microbial composition and balance of the gut microbiota.