Preprint / Version 1

Faecalibaculum rodentium-derived ACT domain protein suppresses CRC development via reducing SLC25A22-mediated glutamate metabolism

This article is a preprint and has not been certified by peer review.

Authors

    Yu Cheng,  
    Yu Cheng
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Ruihan Jiang,  
    Ruihan Jiang
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Hanyong Zhu,  
    Hanyong Zhu
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Yuhang Xue,  
    Yuhang Xue
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Can Zhou,  
    Can Zhou
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Luohang Huang,  
    Luohang Huang
    • National Demonstration Center for Experimental Basic Medical Science Education, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Guojiao Zhu,  
    Guojiao Zhu
    • National Demonstration Center for Experimental Basic Medical Science Education, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Hui Guo,  
    Hui Guo
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Binbin Ji,  
    Binbin Ji
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Miaomiao Sun,  
    Miaomiao Sun
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Yuchen Pan,  
    Yuchen Pan
    • Jiangsu Key Laboratory of Immunity and Metabolism, The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    Jing Han,  
    Jing Han
    • Department of Clinical laboratory Medicine, Jiangnan University Medical Center, Wuxi, Jiangsu, China
    Jing Yang
    Jing Yang
    • Jiangsu Key Laboratory of Immunity and Metabolism,The Department of Pathogenic Biology and Immunology, School of Basic Medical and Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
    • National Demonstration Center for Experimental Basic Medical Science Education, Xuzhou Medical University, Xuzhou, Jiangsu, China
Categories
Immunology & Microbiology
Keywords
F. rodentium; ACT domain protein; CRC; SLC25A22

Abstract

Probiotics exert anti-tumor effects against colorectal cancer (CRC) through multiple pathways, yet their translation into clinical practice remains challenging. Identifying the specific tumor-suppressive molecules derived from these probiotics and their host targets is a promising strategy to address this challenge. We identified the aspartate kinase, chorismate mutase, and prephenate dehydrogenase (TyrA) domain protein (hereafter termed ACT protein) derived from Faecalibaculum rodentium and demonstrated that ACT protein impeded the formation of patient-derived CRC organoids and suppressed CRC growth and metastasis in vivo without overt side effects. Mechanistically, the ACT protein transported into cells via macropinocytosis and directly bound to the mitochondrial glutamate transporter SLC25A22 in CRC cells, leading to decreased SLC25A22-mediated glutamate transport and metabolism, along with reduced level of a-ketoglutarate (a-KG), a metabolic intermediate of glutamate. Conversely, ectopic expression of SLC25A22 or exogenous a-KG supplementation attenuated the growth-inhibitory effect of the ACT protein. Collectively, these observations indicate that ACT protein suppresses CRC growth by directly targeting SLC25A22 and reducing its glutamate transport activity; positioning ACT protein as a candidate inhibitor of SLC25A22 with potential for further translational development.

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Cheng, Y., Jiang, R., Zhu, H., Xue, Y., Zhou, C., Huang, L., Zhu, G., Guo, H., Ji, B., Sun, M., Pan, Y., Han, J., & Yang, J. (2026). Faecalibaculum rodentium-derived ACT domain protein suppresses CRC development via reducing SLC25A22-mediated glutamate metabolism. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.09.24.000350

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