Clostridium butyricum and its metabolite butyrate promote ferroptosis susceptibility in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited therapeutic options. The diversity and composition of intra-tumoral microbiota are associated with PDAC outcomes, and modulating the tumor microbiota has the potential to influence tumor growth and host-immune response. Here, we explore whether intervention with butyrate-producing probiotic can limit PDAC progression. By analyzing TCGA (PAAD) dataset, we found that tumoral butyrate-producing microbiota links to better prognosis and less aggressive features of PDAC. Intervention with Clostridium butyricum or its metabolite butyrate triggered superoxidative stress and intracellular lipid accumulation, which enhanced ferroptosis susceptibility of PDAC. Our study reveals a novel antitumor mechanism of butyrate, and suggests the therapeutic potential of butyrate-producing probiotics in PDAC. Overall design: For RNA preparation, KPC1199 cells were either untreated or treated with 1mM NaB for 24 hours, cells were used for RNA preparation. RNA-seq transcriptome library was prepared following TruSeqTM RNA sample preparation Kit (Illumina) using 5 µg of total RNA, according to manufacturer's instructions.