The clinical significance of physiologic Fluorine-18-fluorodeoxyglucose (18F-FDG) intestinal uptake (IU) based on the predicted link with gut microbiota dysbiosis and inflammatory cytokine production was investigated in a cohort of breast cancer patients. A total of 114 patients were visually classified into the lower or higher IU group. The maximum and mean standardized uptake values of total bowel (TB SUVmax and TB SUVmean) were measured. The gut microbial abundance of the Citrobacter genus of the Enterobacteriaceae family showed a significant positive correlation with TB SUVmax and TB SUVmean (q = 0.021 and q = 0.010). The unclassified Ruminococcaceae showed a significant negative correlation with TB SUVmax (q = 0.010). The level of tumor necrosis factor alpha (TNF-α) was significantly increased in the high IU group (p = 0.017). The TNF-α levels showed a significant positive correlation with TB SUVmax (rho = 0.220 and p = 0.018) and TB SUVmean (rho = 0.250 and p = 0.007). Therefore, our findings suggest that the physiologic intestinal uptake may reflect subclinical inflammation and differences in the composition of the gut microbiome in breast cancer patients.