Exercise, APOE Genotype, and Testosterone Modulate Gut Microbiome-Cognition Associations in Prostate Cancer Survivors

Area of Science:

• Oncology
• Microbiome Research
• Neuroscience

Background:

• Androgen deprivation therapy (ADT) for prostate cancer increases cognitive decline risk.
• Gut microbiome and host genetics/endocrine state may influence cognitive function.

Purpose of the Study:

• Investigate how exercise, APOE genotype, and testosterone interact to affect cognition and gut microbiome in ADT-treated prostate cancer survivors.
• Identify potential microbiome-based biomarkers and therapeutic targets for cognitive health.

Main Methods:

• Subsample of 79 prostate cancer survivors from an exercise trial (strength training, Tai Chi, stretching).
• Collected data on cognition (MoCA), salivary testosterone, APOE genotype, and gut microbiome (16S rRNA sequencing).
• Used statistical models including beta regression, linear models, and DESeq2 for analysis.

Main Results:

• Strength training improved MoCA scores compared to stretching; Tai Chi did not.
• APOE ε4 carriers showed greater testosterone increase with strength training.
• Gut microbiome composition varied with exercise, APOE genotype, and testosterone levels, and correlated with MoCA scores.

Conclusions:

• Endocrine status and APOE genotype modulate the gut microbiome's response to exercise in ADT-treated survivors, influencing cognition.
• Precision survivorship strategies could pair strength training with microbiome monitoring informed by genotype and hormone levels to enhance cognitive performance.