Little is known about the relationship between diet and depression through the gut microbiota among breast cancer patients. This study aimed to examine the dietary intake differences between depressed breast cancer (DBC) and non-depressed breast cancer (NBC) patients, and whether the differences could lead to gut microbiota changes that affect depressive symptoms. Participants completed the Center for Epidemiological Studies-Depression Scale (CES-D) and 24 h dietary recall. Fecal samples of 18 DBC patients and 37 NBC patients were collected for next-generation sequencing. A total of 60 out of 205 breast cancer patients reported significant depressive symptoms suggested by a CES-D score ≥ 16, which might be related to lower intakes of energy, protein, dietary fiber, vitamin A, vitamin B2, niacin, calcium, phosphorus, potassium, iron, zinc, selenium, manganese and tryptophan, and a poor diet quality indicated by a lower total Chinese Healthy Eating Index (CHEI) score. Additionally, NBC patients demonstrated greater gut microbiota diversity and a healthier composition, in which the relative abundances of Proteobacteria and Escherichia-Shigella were both lower than in the DBC patients (p < 0.05). Alpha diversity was a significant mediator between diet quality and depression, while calcium, phosphorus and selenium significantly regulated depression independent of the gut microbiota. Breast cancer-related depressive symptoms might be associated with a poor diet quality via gut microbiota-dependent pathways and lower micronutrient intake via microbiota-independent pathways.

This study examined the association between the energy-adjusted Dietary Inflammatory Index (E-DII)-based dietary inflammatory potential and depressive symptoms (DepS) among patients with breast cancer and explores whether systemic inflammation mediates this association. We assessed dietary intake and DepS in 220 breast cancer patients by three 24 h dietary recalls and the Center for Epidemiological Studies Depression Scale (CES-D), respectively, and determined plasma levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β, IL-4, and IL-6 in 123 blood samples. We found that each one-point increase of E-DII was related to a 53% elevated risk of DepS. Patients with the most pro-inflammatory diets had a 5.13 times higher risk of DepS than those with the most anti-inflammatory diets. Among the E-DII components, vitamin B2, zinc, and iron were inversely associated with DepS risk. Furthermore, E-DII scores were positively associated with CRP and TNF-α. Higher levels of TNF-α and IL-6 were associated with higher DepS risk. A significant mediating effect of TNF-α was revealed between E-DII and DepS. Our findings suggest that a pro-inflammatory diet is positively associated with breast cancer-related DepS, which may be mediated by TNF-α.