Background: Gut microbiome and dietary patterns have been suggested to be associated with depression/anxiety. However, limited effort has been made to explore the effects of possible interactions between diet and microbiome on the risks of depression and anxiety.

Methods: Using the latest genome-wide association studies findings in gut microbiome and dietary habits, polygenic risk scores (PRSs) analysis of gut microbiome and dietary habits was conducted in the UK Biobank cohort. Logistic/linear regression models were applied for evaluating the associations for gut microbiome-PRS, dietary habits-PRS, and their interactions with depression/anxiety status and Patient Health Questionnaire (PHQ-9)/Generalized Anxiety Disorder-7 (GAD-7) score by R software.

Results: We observed 51 common diet-gut microbiome interactions shared by both PHQ score and depression status, such as overall beef intake × genus Sporobacter [hurdle binary (HB)] (P_PHQ = 7.88 × 10^-4, P_{depression status} = 5.86 × 10^-4); carbohydrate × genus Lactococcus (HB) (P_PHQ = 0.0295, P_{depression status} = 0.0150). We detected 41 common diet-gut microbiome interactions shared by GAD score and anxiety status, such as sugar × genus Parasutterella (rank normal transformed) (P_GAD = 5.15 × 10^-3, P_{anxiety status} = 0.0347); tablespoons of raw vegetables per day × family Coriobacteriaceae (HB) (P_GAD = 6.02 × 10^-4, P_{anxiety status} = 0.0345). Some common significant interactions shared by depression and anxiety were identified, such as overall beef intake × genus Sporobacter (HB).

Conclusions: Our study results expanded our understanding of how to comprehensively consider the relationships for dietary habits-gut microbiome interactions with depression and anxiety.