Butyricum菌的益生作用涉及调节疾病和癌症，然而这些调节作用的机制基础仍然大多未知。在这里，我们展示了Butyricum菌通过调节包括MYC在内的关键信号分子来重构CRC细胞的增殖、迁移、干性和肿瘤生长。通过补充Butyricum菌使MYC不稳定，可以抑制癌细胞的增殖/转移，增强5-FU治疗的敏感性并提高抗PD1治疗的反应性。MYC是Thymidylate synthase(TYMS)的转录调节因子，是5-FU的关键靶点。MYC也知影响PD-1表达。机械地说，Butyricum菌对CRC细胞的处理结果是通过增强蛋白酶体介导的泛素化作用，达到分解MYC，从而减轻MYC介导的5-FU耐药性并提高抗PD1免疫疗法的功效。总之，我们的发现揭示了Butyricum菌与CRC细胞信号传导之间以前未被重视的联系，为Butyricum菌在增强化疗/免疫疗法方面的肿瘤发生机制提供了新的见解。

Probiotic roles of Clostridium butyricum (C.B) are involved in regulating disease and cancers, yet the mechanistic basis for these regulatory roles remains largely unknown. Here, we demonstrate that C.B reprograms the proliferation, migration, stemness, and tumor growth in CRC by regulating pivotal signal molecules including MYC. Destabilization of MYC by C.B supplementation suppresses cancer cell proliferation/metastasis, sensitizes 5-FU treatment, and boosts responsiveness of anti-PD1 therapy. MYC is a transcriptional regulator of Thymidylate synthase (TYMS), a key target of the 5-FU. Also MYC is known to impact on PD-1 expression. Mechanistically, C.B treatment of CRC cells results in MYC degradation by enhancing proteasome-mediated ubiquitination, thereby mitigating MYC-mediated 5-FU resistance and boosting anti-PD1 immunotherapeutic efficacy. Together, our findings uncover previously unappreciated links between C.B and CRC cell signaling, providing insight into the tumorigenesis modulating mechanisms of C.B in boosting chemo/immune therapies.