Gut Microbiota’s Critical Role in Castration-Resistant Prostate Cancer

Gut Microbiota's Critical Role in Castration-Resistant Prostate Cancer

Elucidating the Role of Gut Microbiota in CRPC

One of the significant challenges in prostate cancer research is castration-resistant prostate cancer (CRPC). Recent studies have shown that gut microbiota play an essential role in modulating CRPC progression through the TLR4/MyD88/NF-κB pathway.

Gut Microbiota Differences in CRPC and Castration-Sensitive Prostate Cancer

A multidisciplinary approach was used to elucidate the role of gut microbiota in CRPC. The study analyzed 16S rRNA sequencing data from mouse fecal samples, revealing substantial differences in gut microbiota composition between CRPC and castration-sensitive prostate cancer mice, particularly in Firmicutes and Bacteroidetes.

Bacterial Influence on CRPC via Alpha-linolenic Acid Metabolism Pathway

Functional analysis suggested different bacteria may influence CRPC via the α-linolenic acid metabolism pathway. Transcriptome sequencing identified crucial genes and pathways, with rescue experiments confirming the gut microbiota’s role in modulating CRPC progression.

Fecal Microbiota Transplantation (FMT)

In vivo experiments utilizing mouse models and fecal microbiota transplantation (FMT) demonstrated that FMT from healthy control mice could decelerate tumor growth in CRPC mice, reduce TNF-α levels, and inhibit the activation of the TLR4/MyD88/NF-κB signaling pathway.

Gut Microbiota Dysbiosis and CRPC Development through TNF-α Activation of the TLR4/MyD88/NF-κB Signaling Pathway

The study found that gut microbiota dysbiosis may promote CRPC development through TNF-α activation of the TLR4/MyD88/NF-κB signaling pathway. The activation of this pathway by TNF-α has been corroborated by in vitro cell experiments, indicating its role in promoting prostate cancer cell proliferation, migration, and invasion while inhibiting apoptosis.

Related Studies on Gut Microbiota

Several studies support the potential link between gut microbiota dysbiosis and various diseases, including Alzheimer’s disease/Parkinson’s disease, endometrial microbiota disorder, and even cancer. The role of gut microbiota in neurological restoration in a spinal cord injury mouse model has also been studied. Gut microbiota may also play a role in the response to cancer treatment, as shown in individuals with metastatic castrate-resistant prostate cancer progressing on enzalutamide and initiating treatment with anti-PD-1 (pembrolizumab).


The study highlights the critical role of gut microbiota dysbiosis in CRPC development through TNF-α activation of the TLR4/MyD88/NF-κB signaling pathway, potentially linked to α-linolenic acid metabolism. Further research in this area may lead to the development of gut microbiota-based therapies for CRPC treatment and prevention.

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