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.

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.

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)] (PPHQ = 7.88 × 10−4, Pdepression status = 5.86 × 10−4); carbohydrate × genus Lactococcus (HB) (PPHQ = 0.0295, Pdepression 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) (PGAD = 5.15 × 10−3, Panxiety status = 0.0347); tablespoons of raw vegetables per day × family Coriobacteriaceae (HB) (PGAD = 6.02 × 10−4, Panxiety status = 0.0345). Some common significant interactions shared by depression and anxiety were identified, such as overall beef intake × genus Sporobacter (HB).

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

Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear.

The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations.

We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014).

Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.