The impact of adverse childhood experiences on gut microbiota and markers of inflammation is mediated by obesity and depression

Background Adverse childhood experiences (ACEs) are associated with poor health outcomes in adulthood including obesity, psychiatric symptoms, and elevated levels of inflammatory markers. Our previous work found ACEs are associated with altered gut microbiota composition. In the present work, we examined ACE associations with gut microbiota and peripheral measures of inflammation in pregnant women with or without obesity, and explored potential modifying factors including diet and depressive symptoms. Methods Female participants were recruited in the third trimester of pregnancy as part of a larger growth study of African-American infants. Participants were categorized as healthy weight (BMI < 25) or obese (BMI ≥ 30) based on their early pregnancy BMI. They completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and Center for Epidemiologic Studies Depression Scale (CES-D). Stool samples, blood, and dietary data were collected in the third trimester. Shotgun metagenomic sequencing was performed on DNA isolated from stool. Statistical models assessed relationships between gut microbiota and ACE. A false discovery rate (fdr) adjusted p-value q < 0.1 was considered statistically significant. Results 107 women completed questionnaires and provided stool in the third trimester. ACEs were positively associated with BMI and depressive symptom severity but not with gut microbiota composition. Depressive symptoms were significantly negatively associated with abundance of gut Bifidobacterium longum (q = 0.02) and positively associated with Bacteroides thetaiotaomicron (q = 0.02). Path analysis revealed that ACEs predicted pre-pregnancy BMI which predicted elevated inflammatory markers. ACEs also predicted more severe depressive symptoms in pregnancy, which was associated with gut microbiome composition. Finally, ACEs interacted with dietary intake of sugar and whole grains to impact markers of inflammation, the gut microbiome, and enzymes produced by gut microbiota. Discussion ACEs led to two risk pathways in pregnancy: one in which high pre-pregnancy BMI was linked with high levels of serum inflammatory markers during pregnancy, and the other in which greater depressive symptom severity was associated with alterations to the gut microbiome. Further, data suggested ACEs may influence the metabolic potential of the gut microbiome.