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

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.