2. Academic Validation
  3. Intestinal Lachnospiraceae bacterium-derived propionate inhibits the progression of clear cell renal cell carcinoma

Intestinal Lachnospiraceae bacterium-derived propionate inhibits the progression of clear cell renal cell carcinoma

  • Cell Rep Med. 2025 Oct 21;6(10):102410. doi: 10.1016/j.xcrm.2025.102410.
Jun-Yao Xu 1,  Huan Chen 2,  Yao-Yu Yu 3,  Tian-Yi Chen 3,  Yi-Qiu Wang 3,  Wei Xue 3,  Jun-Hua Zheng 4,  Jin-Yao Liu 5,  Wei Zhai 6
Affiliations

Affiliations

  • 1 Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
  • 2 Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai 200127, China; Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 3 Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
  • 4 Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address: zhengjh0471@sina.com.
  • 5 Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai 200127, China; Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address: jyliu@sjtu.edu.cn.
  • 6 Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; Shanghai Immune Therapy Institute State, Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address: jacky_zw2002@hotmail.com.
PMID: 41067230 DOI: 10.1016/j.xcrm.2025.102410
Abstract

Gut microbiota has been reported to be associated with the development of various diseases; however, its interaction with clear cell renal cell carcinoma (ccRCC) remains unknown. To investigate the potential relationship between gut microbiota alterations and ccRCC development, we analyze feces from healthy volunteers and ccRCC patients. We realize that ccRCC patients have a lower abundance of Lachnospiraceae bacterium (L. bacterium). Further experiments reveal that L. bacterium and its metabolite, propionate, exert the antitumor effects. Mechanistically, L. bacterium-derived propionate inhibits tumor cell proliferation and migration by downregulating the expression of homeobox D10 (HOXD10) and its downstream interferon-induced transmembrane protein 1 (IFITM1) and then activating JAK1-STAT1/2 pathway. Furthermore, we design a biofilm-coated L. bacterium as a potential probiotic to improve oral delivery and therapeutic efficacy. Finally, the expanded validation cohort confirms that measuring and targeting L. bacterium and its associated pathways will provide valuable insights into clinical management and improve the prognosis of patients with ccRCC.

Keywords

HOXD10; IFITM1; Lachnospiraceae bacterium; biofilm-coated; clear cell renal cell carcinoma; microbiome; propionate; tumor progression.

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