The potential role of the microbiota in prostate cancer pathogenesis and treatment

Pernigoni, Nicolò; Guo, Christina; Gallagher, Lewis; Yuan, Wei; Colucci, Manuel; Troiani, Martina; Liu, Lei; Maraccani, Luisa; Guccini, Ilaria; Migliorini, Denis; Bono, Johann S. de; Alimonti, Andrea

doi:10.1038/s41585-023-00795-2

Cited by 9 publications

(6 citation statements)

References 180 publications

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“…In recent years, there has been increasing interest in the role of gut microbiota in diseases, with studies reporting a possible association between gut microbiota and PCa [ 46 ]. The gut microbiota consists of microorganisms residing in the gastrointestinal system that interact with the host to regulate behavioral and biochemical processes in the gut [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Xu,

Li,

Liu

et al. 2024

J Exp Clin Cancer Res

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Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.

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Section: Discussionmentioning

confidence: 99%

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Xu,

Li,

Liu

et al. 2024

J Exp Clin Cancer Res

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“…Furthermore, the role of the gut microbiome in prostate cancer endocrine resistance, which occurs through the generation of androgenic steroids, also supports its potential diagnostic capability. Its composition could potentially reveal the endocrine resistance status of a patient with prostate cancer [ 62 ].…”

Section: Indirect Microbiome In Prostate Cancermentioning

confidence: 99%

“…Furthermore, the production of bacterial genotoxins is associated with the occurrence of TMPRSS2-ERG gene fusion, a common early carcinogenic event during the development of prostate cancer. Therefore, the host microbiota provides mechanistic evidence relating to the onset and progression of prostate cancer, suggesting that the profiling and modulation of this microbiome could offer potential avenues for detection and treatment [ 62 ]. Intriguingly, the gut microbiota profile itself has emerged as a novel and useful marker for the detection of high-risk prostate cancer, further implicating the microbiome in the carcinogenesis of this cancer type [ 65 ].…”

Section: Indirect Microbiome In Prostate Cancermentioning

confidence: 99%

Microbiome and Prostate Cancer: Emerging Diagnostic and Therapeutic Opportunities

Kim,

Park,

Choi

et al. 2024

Pharmaceuticals

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This review systematically addresses the correlation between the microbiome and prostate cancer and explores its diagnostic and therapeutic implications. Recent research has indicated an association between the urinary and gut microbiome composition and prostate cancer incidence and progression. Specifically, the urinary microbiome is a potential non-invasive biomarker for early detection and risk evaluation, with altered microbial profiles in prostate cancer patients. This represents an advancement in non-invasive diagnostic approaches to prostate cancer. The role of the gut microbiome in the efficacy of various cancer therapies has recently gained attention. Gut microbiota variations can affect the metabolism and effectiveness of standard treatment modalities, including chemotherapy, immunotherapy, and hormone therapy. This review explores the potential of gut microbiome modification through dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation for improving the treatment response and mitigating adverse effects. Moreover, this review discusses the potential of microbiome profiling for patient stratification and personalized treatment strategies. While the current research identifies the pivotal role of the microbiome in prostate cancer, it also highlights the necessity for further investigations to fully understand these complex interactions and their practical applications in improving patient outcomes in prostate cancer management.

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“…This aligns with our findings, where Ruminococcaceae and Lachnospiraceae are proportionally higher in PCa patients. However, as various bacteria can perform steroid synthesis, further research is needed to identify specific androgenic steroid biosynthetic pathways activated within bacteria [39]. Therefore, the decline in GM diversity may be attributed to changes in testosterone levels [40].…”

Section: Table 2 Quality Assessment Of Studies Included For the Meta-...mentioning

confidence: 99%

Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis

Huang,

Liu,

Wen

et al. 2024

BMC Cancer

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Background Increasing evidence indicates that gut microbiota are closely related to prostate cancer. This study aims to assess the gut microbiota composition in patients with prostate cancer compared to healthy participants, thereby advancing understanding of gut microbiota's role in prostate cancer. Methods A systematic search was conducted across PubMed, Web of Science, and Embase databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of included studies was evaluated using the Newcastle–Ottawa Scale (NOS), and pertinent data were analyzed. The kappa score assessed interrater agreement. Results This study encompassed seven research papers, involving 250 prostate cancer patients and 192 controls. The kappa was 0.93. Meta-analysis results showed that alpha-diversity of gut microbiota in prostate cancer patients was significantly lower than in the control group. In terms of gut microbiota abundance, the ratio of Proteobacteria, Bacteroidia, Clostridia, Bacteroidales, Clostridiales, Prevotellaceae, Lachnospiraceae, Prevotella, Escherichia-Shigella, Faecalibacterium, and Bacteroides was higher in prostate cancer patients. Conversely, the abundance ratio of Actinobacteria, Bacteroidetes, Firmicutes, Selenomonadales, Veillonella, and Megasphaera was higher in the control group. Conclusion Our study reveals differences in alpha-diversity and abundance of gut microbiota between patients with prostate cancer and controls, indicating gut microbiota dysbiosis in those with prostate cancer. However, given the limited quality and quantity of selected studies, further research is necessary to validate these findings.

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The potential role of the microbiota in prostate cancer pathogenesis and treatment

Cited by 9 publications

References 180 publications

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Microbiome and Prostate Cancer: Emerging Diagnostic and Therapeutic Opportunities

Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis

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