Gut Microbiota Metabolic Reprogramming Drives Endocrine and Immune Resistance in Hormone-Dependent Cancers

Area of Science:

• Microbiology
• Endocrinology
• Immunology
• Oncology

Background:

• The gut microbiota acts as an extrinsic endocrine organ, significantly impacting hormone-dependent cancers.
• Microbial metabolic networks (estrobolome, androbolome, etc.) modulate systemic steroid exposure via enzymes like β-glucuronidases.
• Microbe-derived metabolites serve as inter-kingdom messengers, remodeling the tumor immune microenvironment.

Purpose of the Study:

• To elucidate the mechanisms of the microbiota-endocrine-immune axis in hormone-dependent malignancies.
• To explore the bidirectional relationship between anti-tumor drugs and the gut microbiota.
• To propose systems biology strategies for overcoming therapeutic resistance.

Main Methods:

• Review of multi-omic and biochemical evidence.
• Analysis of microbial enzymatic systems (e.g., GUS, steroid-17,20-desmolases).
• Examination of pharmacomicrobiomics and host-microbe holobiont interactions.

Main Results:

• Microbial metabolites modulate the tumor immune microenvironment and contribute to immune evasion.
• Gut microbes can cause resistance to endocrine and immunotherapy by drug inactivation or hormonal precursor supply.
• The gut microbiota influences therapeutic response and pathological evolution of hormone-dependent cancers.

Conclusions:

• Treating the host-microbe system as a unified holobiont is crucial for addressing translational challenges.
• Future research should focus on gnotobiotic models and causal inference for precision therapeutic development.
• Developing tools like microbial enzyme inhibitors and engineered biotherapeutics can overcome resistance in hormone-dependent malignancies.