Erucic Acid, Derived by <i>Lactobacillus Crispatus</i> , Induces Ferroptosis in Cervical Cancer Organoids Through the PPAR‐δ Signaling Pathway

The microbiome present throughout the human body serves a variety of functions. In this study, 16S rRNA sequencing is employed to uncover differences in the abundance of Lactobacillus within the vaginal microbiota between individuals with cervical cancer and those with healthy cervixes. The research further identifies that the metabolite of Lactobacillus crispatus can induce ferroptosis in cervical cancer cells. This conclusion is reached through targeted bacterial culture, patient-derived organoids (PDO) and single-cell RNA sequencing. Erucic acid, identified as a primary metabolite via untargeted metabolomics, acts as a ligand for PPARδ receptor. It has the capacity to activate PPARδ pathway and subsequently trigger downstream fatty acid oxidation (FAO). Excessive enhancement of FAO can generate large amounts of H₂O₂ and O₂-, known as ROS. Utilizing PDO, cell lines and cervical cancer xenograft (CDX) models, the study demonstrate both in vitro and in vivo that the metabolite of L. crispatus, erucic acid, can modulate the proliferation, migration and invasion of cervical cancer by activating the PPAR-δ pathway. This activation leads to fatty acid oxidation, release ROS, and ultimately induces ferroptosis. Therefore, L. crispatus and erucic acid show potential as novel adjuvant therapeutic agents in the treatment of cervical cancer.