Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis

作者：Weibo Zhong, Kaihui Wu, Zining Long, Xumin Zhou, Chuanfan Zhong, Shuo Wang, Houhua Lai, Yufei Guo, Daojun Lv, Jianming Lü, Xiangming Mao · 发表于：Microbiome · 年份：2022 · DOI：10.1186/s40168-022-01289-w · 被引用次数：229 · 研究领域：Gut microbiota and health、Cancer Research and Treatments、Ferroptosis and cancer prognosis

BACKGROUND: The gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts some effect on prostate cancer, as an extra-intestinal tumor, in a contact-independent way remain elusive and deserve exploration. Antibiotic exposure, one of the various factors affecting the gut microbiota community and capable of causing gut dysbiosis, is associated with multiple disorders. This study aims to preliminarily clarify the link between gut dysbiosis and prostate cancer. RESULTS: First, we discovered that perturbing the gut microbiota by consuming broad-spectrum antibiotics in water promoted the growth of subcutaneous and orthotopic tumors in mice. Fecal microbiota transplantation could transmit the effect of antibiotic exposure on tumor growth. Then, 16S rRNA sequencing for mouse feces indicated that the relative abundance of Proteobacteria was significantly higher after antibiotic exposure. Meanwhile, intratumoral lipopolysaccharide (LPS) profoundly increased under the elevation of gut permeability. Both in vivo and in vitro experiments revealed that the NF-κB-IL6-STAT3 axis activated by intratumoral LPS facilitated prostate cancer proliferation and docetaxel chemoresistance. Finally, 16S rRNA sequencing of patients' fecal samples revealed that Proteobacteria was enriched in patients with metastatic prostate cancer and was positively correlated with plasma IL6 level, regional lymph n...