Akkermansia muciniphila Metabolite Inosine Inhibits Castration Resistance in Prostate Cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Gut bacteria, specifically Akkermansia muciniphila (AKK), influence prostate cancer (PCa) treatment response. Inosine, an AKK metabolite, may prevent castration-resistant prostate cancer (CRPC) by modulating the gut-LPS-NF-κB-AR pathway.
Area Of Science
- Oncology
- Microbiome Research
- Metabolomics
Background
- Prostate cancer (PCa) initially responds to androgen deprivation therapy (ADT) but often progresses to castration-resistant prostate cancer (CRPC).
- Factors influencing ADT sensitivity and CRPC development remain incompletely understood.
- Gut microbiota composition has emerged as a potential modulator of cancer progression and treatment response.
Purpose Of The Study
- To investigate the role of gut microbiota, particularly Akkermansia muciniphila (AKK), in ADT sensitivity and CRPC development.
- To identify potential mechanisms linking gut microbiota to CRPC progression.
- To develop a predictive model for CRPC using gut microbiota and clinical data.
Main Methods
- Comparative analysis of gut microbiota in ADT-sensitive and resistant PCa patients and mouse models.
- Untargeted serum metabolomics to identify biomarkers correlated with ADT sensitivity and AKK enrichment.
- Assessment of intestinal permeability and serum lipopolysaccharide (LPS) levels.
- In vivo experiments involving AKK metabolite (inosine) supplementation in mice.
- Analysis of the LPS/NF-κB/AR signaling pathway in tumor tissues.
- Development and validation of a predictive model for CRPC.
Main Results
- Enrichment of Akkermansia muciniphila (AKK) was associated with delayed CRPC development.
- Serum inosine levels were upregulated in the ADT-sensitive group and correlated with AKK abundance.
- Increased intestinal permeability and elevated serum LPS levels were observed in treatment-resistant mice.
- LPS stimulation upregulated p-NF-κB p65 and AR expression in tumors.
- Inosine supplementation alleviated intestinal barrier damage, reduced serum LPS, and inhibited castration resistance via the LPS/NF-κB/AR axis.
- A predictive model combining gut microbiota and clinical information achieved an AUC of 0.729 for CRPC prediction.
Conclusions
- Gut microbiota, especially AKK, plays a significant role in modulating prostate cancer response to ADT.
- The LPS/NF-κB/AR axis represents a key pathway through which gut microbiota influences CRPC development.
- Inosine, an AKK metabolite, shows therapeutic potential for preventing or delaying CRPC.
- Gut microbiota and inosine are promising prognostic indicators and therapeutic targets for CRPC.
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