Abstract
Genetic predisposition and environmental factors, including psychological stress, play prominent roles in driving the development and progression of colorectal neoplasms. However, the mechanisms through which chronic stress drives the progression of colorectal neoplasm remain unclear. The gut microbiota is closely linked to chronic psychological stress (chronic stress) and colorectal neoplasms. Here, we found that chronic stress significantly promoted tumor growth in patients with colorectal cancer and mouse models of colitis-associated colorectal cancer, while concurrently reducing the abundance of Akkermansia muciniphila in fecal and tumor samples. Restoring the A. muciniphila abundance mitigated the tumor-promoting effects of chronic stress. Furthermore, we identified A. muciniphila outer membrane vesicles as key mediators of the protective effect of this microbe. In conclusion, A. muciniphila alleviates chronic stress-induced colorectal neoplasm growth by releasing outer membrane vesicles. These findings highlight a connection among chronic stress, the gut microbiota, and colorectal neoplasms, providing a theoretical foundation for therapeutic strategies aimed at managing tumor progression in patients with colorectal cancer experiencing chronic stress.