The consumption of ultra-processed foods and drinks (UPF) has been associated with depression and inflammation and preclinical studies showed that some UPF components disrupt the amygdala-hippocampal complex. We combine diet, clinical and brain imaging data to investigate the relationship between the UPF consumption, depressive symptoms, and brain volumes in humans, considering interactions with obesity, and the mediation effect of inflammation biomarkers. One-hundred fifty-two adults underwent diet, depressive symptoms, anatomic magnetic resonance imaging assessments and laboratory tests. Relationships between the % of UPF consumption (in grams) of the total diet, depressive symptoms, and gray matter brain volumes were explored using several adjusted regression models, and in interaction with the presence of obesity. Whether inflammatory biomarkers (i.e., white blood cell count, lipopolysaccharide-binding protein, c-reactive protein) mediate the previous associations was investigated using R mediation package. High UPF consumption was associated with higher depressive symptoms in all participants (β = 0.178, CI = 0.008-0.261) and in those with obesity (β = 0.214, CI = -0.004-0.333). Higher consumption was also associated with lower volumes in the posterior cingulate cortex and the left amygdala, which in the participants with obesity also encompassed the left ventral putamen and the dorsal frontal cortex. White blood count levels mediated the association between UPF consumption and depressive symptoms (p = 0.022). The present study precludes any causal conclusions. UPF consumption is associated with depressive symptoms and lower volumes within the mesocorticolimbic brain network implicated in reward processes and conflict monitoring. Associations were partially dependent on obesity and white blood cell count.

Background: Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. Methods: We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics. Results: An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism ( thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor’s bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient’s mice. Conclusion: These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.

Adolescents show one of the highest rates of ultra-processed foods and drinks (UPF) consumption, and studies indicate an association between their consumption and internalizing problems. We aim to investigate whether UPF consumption associates with dysfunctions in other psychosocial domains, as well as sex effects. In 560 Spanish adolescents (14–17 years old), we assessed the UPF products consumed in the previous day, fruits and vegetables consumption (servings/day), and physical activity (days/week). Psychosocial functioning (total and subscales) was assessed through the Pediatric Symptom Checklist–Youth self-report. Associations between UPF and psychosocial functioning were assessed using linear regression models, adjusting for sex, age, fruits and vegetables consumption, and physical activity. Sex-specific associations were also explored. Participants reported a daily consumption of 7.72 UPF servings per day, with male adolescents showing higher consumption than female adolescents. Consumption of fruits and vegetables and physical activity levels were lower than recommended. Psychosocial impairment was present in 26.2% of the participants. Higher UPF consumption was associated with higher presence of depressive symptoms and internalizing and externalizing problems in the whole sample and in male adolescents. The present study supports previous studies suggesting that UPF consumption may interact with mental health problems and indicates that these effects may go beyond internalizing problems.