Chemotherapy-driven intestinal dysbiosis and indole-3-propionic acid rewire myelopoiesis to promote a metastasis-refractory state.

ABSTRACT: The contribution of chemotherapy-induced tissue injury to individual susceptibility to metastasis remains largely unexplored. We report that chemotherapy indirectly prevents colorectal cancer (CRC) liver metastases by inducing a lasting systemic "chemomemory". Chemotherapy-induced intestinal mucositis alters nutrient availability, promoting the expansion of tryptophan-metabolizing bacteria and production of the microbial metabolite indole-3-propionic acid (IPA). IPA reprograms bone marrow myelopoiesis by redirecting common myeloid progenitor fate toward the macrophage lineage, limiting generation of immunosuppressive Ly6C^highCCR2⁺ monocytes. This shift enhances CD4⁺ T cell antitumor function by promoting Th1 differentiation and spatially reorganizing CD8

SUBMITTER: Bersier L 

PROVIDER: S-EPMC12827274 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature