Associations Between Physical Activity Measurement Modality and Gut Microbiome in Breast Cancer Survivors

Background/Objectives: Physical activity (PA), physiological fitness, and the gut microbiome have each been linked to health outcomes among breast cancer survivors (BCS); however, these associations have been inconsistent. Few studies have directly compared the associations of self-reported PA, accelerometer-derived PA, and physiological fitness with the gut microbiome within the same population. This study evaluated whether associations with gut microbiome outcomes vary by PA and fitness measurement modality in post-primary treatment BCS. Methods: Baseline data from 69 BCS enrolled in a randomized controlled trial were analyzed. PA was assessed using self-reported moderate-to-vigorous PA (MVPA) and accelerometer-derived light PA (LPA), MVPA, and sedentary behaviors. Physiological fitness was evaluated using peak oxygen uptake (V˙O2peak) and related fitness metrics. Gut microbiome outcomes included α-diversity, β-diversity, and exploratory taxa-level analyses derived from 16S rRNA sequencing. Associations were evaluated using correlation and regression analyses, with adjustment for relevant clinical covariates. Results: Accelerometer-derived PA, particularly MVPA, demonstrated the strongest and most consistent associations with α-diversity and β-diversity, whereas physiological fitness measures showed only weak associations. Sedentary behavior was inversely associated with both diversity metrics, while self-reported MVPA was not associated with diversity indices. Medication burden and comorbidity status attenuated several PA-microbiome associations, and no taxa-level associations remained significant after correction for multiple testing. Conclusions: Associations between PA, fitness, and gut microbiome outcomes varied according to measurement modality. Accelerometer-derived MVPA demonstrated more consistent associations with microbiome diversity and composition than self-reported MVPA or physiological fitness. Future studies should incorporate multiple complementary measures of PA and fitness when examining PA–microbiome relationships.