Repressed Blautia-acetate immunological axis underlies chronic stress promoted breast cancer progression

Chronic stress is a indispensable factor in promoting cancer progression; however, whether and how microbial and metabolic signals are involved remains largely unclear. Here, we developed a systemic approach to temporospatial mapping of gut microbiome and the relevant metabolites and revealed a causal relationship between the reduced Blautia-produced acetate and chronic stress-promoted breast cancer progression. Blautia and acetate treatment amplified the antitumor responses of CD8+ T cells, and reversed stress-promoted breast cancer progression. In humans, the patients with depression exhibited a lower amount of fecal Blautia and acetate in comparison with healthy controls, and the depressed breast cancer patients also exhibited a reduced amount of serum acetate, correlating with the decreased abundance of tumor-infiltrated CD8+ T cells. Collectively, our findings suggest that reduced Blautia-produced acetate represents an underlying cause of chronic stress-promoted breast cancer progression, shedding lights in better understanding of how microbial and metabolic signals are involved in stress-promoted cancer progression, from which new therapeutic options can be exploited.