BACKGROUNDA growing body of studies revealed that enteric dysbacteriosis could result in depression via the "gut-microbiota-brain axis" (GMBA). Whether probiotics, prebiotics, and synbiotics supplements could lessen the risk of depression is a topic attracting attention. This research was conducted to evaluate the relationship between probiotics, prebiotics, synbiotics, or yogurt supplements and depression with large cross-sectional data.METHODSAll data in our research was sourced from the National Health and Nutrition Examination Survey (NHANES) (2005-2016). Probiotics, prebiotics, synbiotics, and yogurt supplements were identified using Food Frequency Questionnaire (FFQ) and Dietary Supplement Use 30-Day (DSQ). We employed the Patient Health Questionnaire (PHQ-9) for evaluating depression. Logistic regression and the Kaplan-Meier curve were performed to examine the correlation between the supplements and depression, as well as mortality.RESULTSA total of 17,745 adult participants were selected. The participants who supplemented probiotics, prebiotics, synbiotics, or yogurt products in the last 30 days showed a significantly lower depression rate compared with those who didn't. Specifically, the supplements could alleviate depressive symptoms including sad, anhedonia, sleep problems, fatigue, appetite changes, and psychomotor changes. This association was more prominent in specific populations such as the population aged 40-60 years, male, whites. The supplements also show more significant effects on increasing survival rates in patients with mild depression.LIMITATIONCross-sectional analysis reveals correlative but not causative association.CONCLUSIONBased on the analysis of NHANES data, our research highlights the positive effect the supplements have on preventing depression, relieving depressive symptoms and increasing survival rates. This effect varied across populations.