Therapeutic potential of Clostridium butyricum anticancer effects in colorectal cancer

ABSTRACT

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.

KEYWORDS:

• Clostridium butyricum
• MYC
• ubiquitination
• TYMS
• 5-FU
• immunotherapy
• Anti-PD1

Acknowledgments

The authors would like to thank Peng Zhang for his technical help.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

All data supporting the findings of this study are available from the corresponding author upon request. RNA-Seq data for this article can be accessed online at https://www.ncbi.nlm.nih.gov/sra/PRJNA880980.

Author contributions

Study design: H.X., M.H.L; Sample collection and processing: H.X.,H.L.; PDO experiment: H.X.; Bioinformatics analysis and statistics: H.X.; Manuscript preparation: H.X., H.L., M.H.L; Manuscript writing: M.H.L

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2186114.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the National Key R&D Program of China (2020YFA0803300, 2018YFC0910300), the National Natural Science Foundation of China (81630072), Shenzhen Municipal Government of China (KQTD20170810160226082), and the Scientific and Technological Project of Guangzhou, China (202206010167).